Document:

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                                                                  EXHIBIT 10.18

                              AMENDED AND RESTATED
                             SHAREHOLDERS AGREEMENT

                              ARRAY BIOPHARMA INC.

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<TABLE>
<CAPTION>
                                                  TABLE OF CONTENTS                                            PAGE
<S>                                                                                                           <C>
RECITALS .........................................................................................................1

SECTION 1.        DEFINITIONS.....................................................................................1

SECTION 2.        RESTRICTIONS ON SALE OR TRANSFER OF SHARES......................................................3
                  2.1      General Prohibition....................................................................3
                  2.2      Right of First Offer...................................................................3
                  2.3      Tag-Along Rights.......................................................................5
                  2.4      Exempt Transfer........................................................................5
                  2.5      Related Party..........................................................................6
                  2.6      Opinion of Counsel.....................................................................6

SECTION 3.        RIGHTS OF FIRST REFUSAL ........................................................................6
                  3.1      Subsequent Offerings...................................................................6
                  3.2      Exercise of Rights.....................................................................6
                  3.3      Company Sale...........................................................................7
                  3.4      Termination of Rights of First Refusal.................................................7
                  3.5      Transfer of Rights of First Refusal....................................................7
                  3.6      Excluded Securities....................................................................7

SECTION 4.        NUMBER OF DIRECTORS; BOARD COMMITTEES ..........................................................8
                  4.1.     Number of Directors....................................................................8
                  4.2.     Voting; Board of Directors............................................................ 8
                  4.3      Vacancies of Directors.................................................................8
                  4.4      Major Decisions of the Board of Directors..............................................8
                  4.5      Observation Rights; Board of Directors ................................................9

SECTION 5.        REMEDIES FOR BREACH............................................................................ 9
                  5.1.     General................................................................................9
                  5.2.     No Personal Liability..................................................................9

SECTION 6.        LEGEND ON STOCK CERTIFICATES....................................................................9

SECTION 7.        MISCELLANEOUS..................................................................................10
                  7.1      Modifications and Waivers.............................................................10
                  7.2      Rights and Obligations of Third Parties...............................................10
                  7.3      Notices...............................................................................10
                  7.4      Entire Agreement......................................................................11
                  7.5      Severability..........................................................................11
                  7.6      Headings..............................................................................11
                  7.7      Counterparts..........................................................................11
                  7.8      Governing Law.........................................................................11
                  7.9      Delays or Omissions...................................................................11
                  7.10     Arbitration...........................................................................11
                  7.11     Termination...........................................................................12
</TABLE>

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                  AMENDED AND RESTATED SHAREHOLDERS AGREEMENT

         This Amended and Restated Shareholders Agreement (the "Agreement") is
entered into as of the 16th day of November, 1999, by and among ARRAY
BIOPHARMA, INC., a Delaware corporation (the "Company"), each of those persons
listed on the signature pages hereto as either "Investors" or "Founders" and
those certain other holders of the Company's capital stock as may be identified
on the signature pages attached hereto from time to time (the "Holders") (the
Investors, Founders and Holders are sometimes referred to collectively as the
"Shareholders").

                                    RECITALS

         A.       The Company, Investors and Founders previously entered into
                  that certain Shareholders Agreement, dated as of May 18, 1998
                  (the "Shareholders Agreement"), as amended August 7, 1998.

         B.       The Company, Investors and Founders have entered into that
                  certain Series B Preferred Stock Purchase Agreement, dated of
                  even date herewith (the "Purchase Agreement"), pursuant to
                  which the Company will issue and sell, and the Investors and
                  Founders will purchase, certain shares of the Company's
                  Series B Preferred Stock (the "Stock").

         C.       As a condition to the closing of the purchase of the Stock
                  under the Purchase Agreement, the Company, Investors and
                  Founders desire to amend and restate the Shareholders
                  Agreement as provided herein.

                                   AGREEMENT

         NOW, THEREFORE, in consideration of the foregoing, the mutual
covenants and agreements herein contained and other good and valuable
consideration, the receipt and adequacy of which is hereby acknowledged, the
parties hereby agree as follows:

SECTION 1. DEFINITIONS

         As used in this Agreement, the following terms shall have the
following meanings:

         "Affiliate" shall mean, with respect to any specified Person, any
Person that, directly or indirectly, controls, is controlled by, or is under
common control with, such specified Person, whether by contract, through one or
more intermediaries, or otherwise. Unless otherwise qualified, all references
to an "Affiliate" or to "Affiliates" in this Agreement shall refer to an
Affiliate or Affiliates of the Company.

         "As Converted Basis" shall mean, with reference to convertible
securities of the Company, the number of shares of Common Stock into which such
securities may be converted while giving effect to the exercise of comparable
conversion rights held by others.

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         "Business Days" shall mean all days other than Saturday or Sunday or
any day on which banking institutions in Denver, Colorado are authorized or
obligated by law to close.

         "Common Stock" shall mean (i) the common stock of the Company, $0.001
par value per share; (ii) any other capital stock of the Company into which
such common stock is converted, exchanged, reclassified or reconstituted; (iii)
any warrants or options exercisable for any of the foregoing; and (iv) any
right to receive any of the foregoing other than upon conversion of any
security convertible into any of the foregoing.

         "Exchange Act" means the Securities Exchange Act of 1934, amended from
time to time.

         "Fair Market Value" shall mean the fair market value per share of
Common Stock as determined in good faith by the Board of Directors.

         "Person" means any natural person, incorporated entity, limited or
general partnership, business trust, association, joint venture, limited
liability company, agency (government or private), division, political
sovereign, or subdivision or instrumentality, or any other entity of any kind,
including those groups identified as "persons" in ss.ss.13(d)(3) and 14(d)(2)
of the Exchange Act, and any successor, by merger or otherwise, of such entity.

         "Preferred Stock" shall mean any series of preferred stock of the
Company, including, without limitation, the Series A Preferred Stock and the
Series B Preferred Stock.

         "Qualifying IPO" shall mean an initial public offering of Common Stock
pursuant to an effective registration statement under the Securities Act at a
price per share of at least $8.00 and resulting in at least $20 million of
gross proceeds (before underwriting discounts and commissions).

         "Securities Act" means the Securities Act of 1933, as amended from
time to time.

         "Series A Preferred Stock" shall mean the Series A Preferred Stock,
$0.001 par value per share, of the Company, or any other capital stock of the
Company into which such stock is reclassified or reconstituted or any
securities convertible into, or exchangeable or exercisable for, any of the
foregoing, in each case, at any time outstanding.

         "Series B Preferred Stock" shall mean the Series B Preferred Stock,
$0.001 par value per share, of the Company, or any other capital stock of the
Company into which such stock is reclassified or reconstituted or any
securities convertible into, or exchangeable or exercisable for, any of the
foregoing, in each case, at any time outstanding.

         "Shares" shall mean (i) any shares of Common Stock; (ii) any shares of
Preferred Stock; (iii) any shares of any other capital stock of the Company;
and (iv) any securities convertible into, or exchangeable or exercisable for,
any of the foregoing, in each case, at any time outstanding.

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         Other Defined Terms. The following terms shall have the meanings
specified in the Sections set forth below:

<TABLE>
<CAPTION>
                  Term                                        Section
                  ----                                        -------
<S>                                                          <C>
                  Exempt Transfer                             2.4
                  Related Party                               2.5
                  Right of First Offer                        2.2(a)
                  Seller                                      2.2(a)
                  Tag-Along Notice, Right, Shareholders       2.3
                  Transfer                                    2.1
                  Transfer Offer                              2.2(a)
                  Transfer Terms                              2.3(a)
</TABLE>

SECTION 2. RESTRICTIONS ON SALE OR TRANSFER OF SHARES

         2.1 General Prohibition. No Shareholder shall sell, assign, transfer,
give, pledge, encumber or in any way dispose of, (collectively, a "Transfer")
any Shares, or enter into an agreement to Transfer any Shares, other than an
agreement that is expressly subject to compliance with the provisions of this
Article 2, unless (a) such Shareholder has complied with the provisions of this
Article 2, and (b) the transferee of any such Shares has agreed to be bound by
the terms of, and become a party to, this Agreement. Any purported Transfer in
violation of any provision of this Agreement shall be void and ineffective and
shall not operate to Transfer any interest or title to the purported
transferee. The prohibitions set forth in this Section 2.1 shall include, but
shall not be limited to, unless specifically permitted hereunder, any agreement
to limit, restrict or grant any voting rights with respect to any Shares.

         2.2 Right of First Offer.

                  (a) If at any time, other than pursuant to an Exempt
Transfer, any Shareholder or their Related Party (each, a "Seller") desires to
Transfer any or all of the Shares or any rights to Shares held by such Seller
to any person, such Seller shall reduce to writing the terms pursuant to which
Seller desires to Transfer such Shares (a "Transfer Offer"). The Transfer Offer
shall identify the number of Shares to be transferred, the consideration for
the Shares, the identity of any third party offeror, and all the other terms
and conditions of such Transfer Offer. The Seller shall deliver the Transfer
Offer to the Company, Founders and Investors. Notwithstanding anything to the
contrary contained herein, for any Transfer by an Investor or Founder, or their
Exempt Transferees, of (i) Series A Preferred Stock, the rights set forth in
this Section 2.2 shall be limited to Transfer Offerees holding Series A
Preferred Stock, or (ii) Series B Preferred Stock, the rights set forth in this
Section 2.2 shall be limited to Transfer Offerees holding Series B Preferred
Stock and Section 2.3 shall not apply to any such Transfer of Series B
Preferred Stock.

                  (b) Subject to the conditions set forth in Section 2.2(a),
each Investor and Founder (collectively, the "Transfer Offerees") shall have
the right to purchase up to its pro rata

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share of the Shares offered in the Transfer Offer, on the terms therein,
exercisable by written notice to the Seller within 20 days of receipt of the
Transfer Offer. For purposes of this Section 2.2(b), pro-rata share is
determined by the respective Share holdings of each Transfer Offeree, expressed
as a percentage of the total number of Shares held by all Transfer Offerees, on
an As Converted Basis (including all shares of Common Stock issued or issuable
upon the exercise of any outstanding options or warrants).

                  (c) If, after expiration of the 20 day period in Section
2.2(b), any Transfer Offer Shares remain unsubscribed, then the Seller shall,
by written notice (the "Second Notice") no later than 5 days after expiration
of the 20 day period, offer the Transfer Offerees who have elected to purchase
Shares under Section 2.2(b) the right to purchase their pro-rata share of the
unsubscribed Shares, such right exercisable by written notice to the Seller
within 5 business days of receipt of the Second Notice. The Second Notice shall
state the number of unsubscribed Shares, and the pro-rata share of those Shares
for each Transfer Offeree. For purposes of this Section 2.2(c), pro-rata share
is determined by the respective Share holdings of each Transfer Offeree,
expressed as a percentage of the total number of Shares held by all Transfer
Offerees electing to purchase unsubscribed Shares, on an As Converted Basis,
including all shares of Common Stock issued or issuable upon the exercise of
any outstanding options or warrants. Transfer Offerees electing to purchase
unsubscribed Shares under this Section 2.2 (c) may assign to each other some or
all of their pro-rata share.

                  (d) The closing of the purchases of Shares by the Transfer
Offerees shall take place at the principal office of the Company at least 20
business days after the expiration of the Transfer Offer, or at least 20
business days after expiration of the Second Notice, whichever is later. At
such closing, the Transfer Offerees shall deliver a certified check or checks
in the appropriate amount to the Seller against delivery of certificates
representing the Shares so purchased, duly endorsed in blank for transfer or
accompanied by a stock power duly executed in blank. In the event that the
consideration specified in the Transfer Offer is other than cash, then the
Transfer Offerees may, at their option, deliver at such closing cash, in lieu
of such other consideration, in an amount equal to the fair market value of
such other consideration (as agreed upon by the parties or as determined by an
independent appraisal, agreed upon by the parties).

                  (e) If the Transfer Offerees agree collectively to purchase
less than all of the Shares offered in the Transfer Offer, the Seller shall
have the right, for a period of 90 days from expiration of the Transfer Offer,
to Transfer any remaining Shares to any person at a price not less than and on
terms no more favorable than contained in the Transfer Offer. If the Seller has
not completed the sale of all the Shares offered under the Transfer Offer
within such 90 day period, the Seller shall no longer be permitted to Transfer
such Transfer Stock pursuant to this Section 2.2 without again fully complying
with the provisions hereof.

                  (f) Notwithstanding the foregoing, no sale may be made to any
third party unless such third party agrees in writing, in form and substance
reasonably acceptable to the Company, to be bound by the provisions of this
Agreement. Promptly after any sale pursuant to this Section 2.2, the Seller
shall notify the Company of the consummation thereof and shall

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furnish such evidence of the completion (including time of completion) of such
sale and of the terms thereof as the Company may reasonably request.

         2.3 Tag-Along Rights.

                   (a) If (i) one or more Sellers at any time, or from time to
time, in one transaction or in a series of related transactions, propose to
Transfer to a Third Party (other than in an Exempt Transfer) Shares
representing more than 10 percent of the Company's outstanding Common Stock, on
an As Converted Basis (including all shares of Common Stock issued or issuable
upon the exercise of any outstanding warrants or options); and (ii) such
Sellers have complied with Section 2.2 hereof with respect to such proposed
Transfer to such Third Party and are entitled to proceed with such Transfer,
then each of the Founders and the Investors (other than any Founder or Investor
who is also the Seller) (collectively, the "Tag-Along Shareholders") shall have
the right (the "Tag-Along Right") to require the proposed purchaser to purchase
from such Tag-Along Shareholder up to such Tag-Along Shareholder's pro rata
portion of the Shares to be Transferred (determined for purposes of this
Section 2.3 by multiplying the total number of Shares to be purchased by a
fraction, the numerator of which is the total number of Shares owned by the
Tag-Along Shareholder, and the denominator of which is the total number of
Shares owned by the Seller(s) and all Tag-Along Shareholders). Any Shares
purchased from Tag-Along Shareholders pursuant to this Section 2.3 shall be
paid for in cash, at the same price per share and upon the same terms and
conditions as such proposed Transfer by the Seller (the "Transfer Terms").

                  (b) The Seller(s) shall notify promptly the Tag-Along
Shareholders in the event they propose to make a Transfer giving rise to the
Tag-Along Right, and shall furnish the Tag-Along Shareholders with the Transfer
Terms and a copy of any written offer or agreement pertaining thereto. The
Tag-Along Right may be exercised by any Tag-Along Shareholder by delivery of a
written notice to each Seller proposing to sell Shares (the "Tag-Along Notice")
within 15 Business Days following its receipt of such notice from each such
Seller, stating the number of Shares that such Tag-Along Shareholder proposes
to include in the Transfer. In the event that the proposed purchaser does not
purchase the specified number of Shares from the Tag-Along Shareholders on the
Transfer Terms, and subject to the same terms and conditions as are applicable
to the Seller(s) in such transaction, then the Seller(s) shall not be permitted
to sell any Shares to the proposed purchaser in the proposed Transfer.

         2.4 Exempt Transfer. As used herein, the term "Exempt Transfer" shall
mean (a) Transfers between any Shareholder and its respective Related Parties;
(b) Transfers pursuant to an effective registration statement under the
Securities Act; (c) Transfers that are approved in writing by all Shareholders;
(d) Transfers by a Shareholder of Shares as collateral security for loans made
to such Shareholder, the proceeds of which are used by the transferring
Shareholder in the exercise of such Shareholder's rights under Section 2.2 of
this Agreement; (e) Transfers between a Shareholder and the Company pursuant to
a validly adopted stock purchase plan for employees and directors of, or
consultants to, the Company; and (f) Transfers between existing Shareholders
provided that the proposed transferror of any such Transfer delivers notice of
all of the terms of such Transfer to all other Shareholders at least 20 days
prior to the closing of such

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Transfer; provided, further, that (i) no such Transfer pursuant to this Section
2.4 (except as set forth in clause (d) above) shall be an Exempt Transfer
unless the transferee agrees in writing to be bound by this Agreement as a
Shareholder with respect to the Shares received by such transferee, and (ii)
the foreclosure upon any lien, pledge or security interest granted pursuant to
an Exempt Transfer described in clause (d) and any Transfer of such Shares
subsequent to such foreclosure shall not constitute an Exempt Transfer and
shall be subject to all provisions of this Agreement, including, without
limitation, the provisions of this Article 2.

         2.5 Related Party. As used herein, the term "Related Party" with
respect to any Shareholder means, as of the time of any Transfer, (a) any
person or entity that, directly or indirectly, through one or more
intermediaries, has voting control of, or is under common voting control with,
such Shareholder; (b) with respect to individuals, such Shareholder's spouse,
parents, children, siblings and/or grandchildren; (c) a trust, corporation,
partnership or other entity, whose beneficiaries, shareholders, partners, or
owners, or other persons or entities holding a controlling interest in which,
consist of such Shareholder and/or such other persons or entities referred to
in the immediately preceding clauses (a) or (b); and (d) with respect to any
Shareholder which is a partnership, a limited liability company or a
corporation, such Shareholders' current partners, members or shareholders in
proportion to their ownership.

         2.6 Opinion of Counsel. Notwithstanding any provision herein to the
contrary, if timely requested by the Company, no Shareholder shall Transfer any
Shares unless such Shareholder shall first obtain an opinion of counsel
satisfactory to the Company to the effect that such Transfer is either exempt
from the registration provisions of the Securities Act or that the Securities
Act is inapplicable to such Transfer.

SECTION 3. RIGHTS OF FIRST REFUSAL

         3.1 Subsequent Offerings. Each Investor and Founder shall have a right
of first refusal to purchase its pro rata share of all Equity Securities (as
defined below) that the Company may from time to time propose to sell and issue
after the date of this Agreement, other than Equity Securities excluded by
Section 3.6 hereof. For purposes of this Section 3, each Investor's and
Founder's pro rata share is equal to the ratio of (a) the number of shares of
the Company's Common Stock that such Investor or Founder is a holder of on an
As Converted Basis immediately prior to the issuance of such Equity Securities
to (b) the total number of shares of the Company's outstanding Common Stock on
an As Converted Basis held by all Investors and Founders immediately prior to
the issuance of the Equity Securities. The term "Equity Securities" shall mean
(i) any Common Stock, Preferred Stock or other security of the Company; (ii)
any security convertible, with or without consideration, into any Common Stock,
Preferred Stock or other security (including any option to purchase such a
convertible security); (iii) any security carrying any warrant or right to
subscribe to or purchase any Common Stock, Preferred Stock or other security;
or (iv) any such warrant or right.

         3.2 Exercise of Rights. If the Company proposes to sell and issue any
Equity Securities, it shall give each Investor and Founder written notice of
its intention, describing the Equity Securities, the price and the terms and
conditions upon which the Company proposes to

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issue the same. Each Investor and Founder shall have 20 days from the giving of
such notice to elect to purchase its pro rata share of the Equity Securities
for the price and upon the terms and conditions specified in the Company's
notice by giving written notice to the Company and stating therein the quantity
of Equity Securities to be purchased. Notwithstanding the foregoing, the
Company shall not be required to offer or sell such Equity Securities to any
Investor or Founder that would cause the Company to be in violation of
applicable federal securities laws by virtue of such offer or sale.

         3.3 Company Sale. The Company shall have 120 days from the giving of
notice under Section 3.2 to sell any Equity Securities not purchased under
Section 3.2, at a price and upon general terms and conditions materially no
more favorable than specified in such notice, without offering such Equity
Securities again to the Investors and Founders in the manner provided above.

         3.4 Termination of Rights of First Refusal. The rights of first
refusal established by this Section 3 shall not apply to, and shall terminate
upon, the effective date of the registration statement pertaining to a
Qualifying IPO.

         3.5 Transfer of Rights of First Refusal. The rights of first refusal
of each Investor and Founder under this Section 3 may be transferred to the
same parties, subject to the same restrictions as any transfer of registration
rights pursuant to the Investor Rights Agreement, dated of even date herewith,
by and between the Company, the Investors and the Founders.

         3.6 Excluded Securities. The rights of first refusal established by
this Section 3 shall have no application to any of the following Equity
Securities:

                  (a) to the shares of Common Stock (and/or options, warrants
or other Common Stock purchase rights issued pursuant to options, warrants or
other rights) issued or to be issued to employees, officers or directors of, or
consultants or advisors to the Company or any subsidiary, pursuant to any valid
option plan of the Company;

                  (b) stock issued pursuant to any options, warrants or other
rights outstanding as of the date of this Agreement;

                  (c) any Equity Securities issued pursuant to the Purchase
Agreement;

                  (d) any Equity Securities issued for consideration other than
cash pursuant to a merger, consolidation, acquisition or similar business
combination;

                  (e) shares of Common Stock issued in connection with any
stock split, stock dividend or recapitalization by the Company;

                  (f) shares of Common Stock issued upon conversion of the
Preferred Stock or any other shares of capital stock of the Company convertible
into Common Stock; and

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                  (g) any Equity Securities that are issued by the Company
pursuant to a registration statement filed under the Securities Act.

SECTION 4. NUMBER OF DIRECTORS; BOARD COMMITTEES

         4.1 Number of Directors. At all times during which this Agreement
remains in effect, the Board of Directors of the Company (the "Board of
Directors") shall consist of no less than seven directors and no more than nine
directors.

         4.2 Voting; Board of Directors. The Board shall be 7 members
initially. Each Shareholder hereby agrees, at all times during which this
Agreement remains in effect, to vote its Shares entitled to vote upon the
election of directors such that (i) at least three individuals designated by
the Founders are elected to the Board; and (ii) at least four individuals
designated by the Investors are elected to the Board; provided, however, that
the fourth member designated by the Investors shall be with the consent of
Founders. The Investors agree to vote their Shares such that at least one
nominee of Frazier Healthcare II, L.P. is elected to the Board. The Founders
shall be given notice of, and shall be entitled to attend, all Board Meetings.

         4.3 Vacancies of Directors. In the event that any vacancy occurs on
the Board of Directors because of death, disability, resignation, retirement or
removal of any director during the term in which the provisions for election of
directors set forth in Section 4.2 remain in effect, each Shareholder shall
vote all of its Shares in a manner to cause such vacancy to be filled so as to
give effect to the provisions of Section 4.2. Any election necessary to fill
any such vacancy shall be held as soon as practicable after the occurrence of
any such vacancy, but in any event within 30 days after the occurrence thereof.

         4.4 Major Decisions of the Board of Directors.

                  (a) In addition to any vote or consent of the shareholders
required by law, the Company's Certificate of Incorporation or any other
agreement to which the Company is a party, the affirmative consent of at least
a majority of the members of the Board of Directors (as opposed to a majority
of the members of the Board of Directors that are present at a meeting and
entitled to vote on a particular issue) shall be necessary for effecting,
validating or permitting:

                           (i) any hiring, termination or demotion of any
elected officer of the Company; or

                           (ii) any consolidation or merger involving the
Company (other than a consolidation or merger in which the Company is the
surviving entity and no change in the capital stock or ownership of the Company
occurs), any transaction or series of transactions in which an excess of 50% of
the Company's voting power is transferred, or any dissolution, liquidation, or
winding up of the Company, or any sale of more than 50% of the assets of the
Company, or any agreement to become so obligated.

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                  (b) In addition to any vote or consent of the shareholders
required by law, the Company's Certificate of Incorporation or any other
agreement to which the Company is a party, the affirmative consent of majority
of the holders of the Company's common stock, shall be necessary for effecting,
validating or permitting any transaction specified in Section 4.2(a)(ii) above.

         4.5 Observation Rights; Board of Directors. The following Investors
shall have the right to appoint observers to the Board of Directors (the "Board
Observers"): Frazier Healthcare II, L.P. (one Board Observer); ARCH Venture
Fund III, L.P. (two Board Observers); and Rovent II Limited Partnership (one
Board Observer); provided, however, that one of the Board Observers for ARCH
Venture Fund III, L.P. shall be Robert Nelson or Steve Lazarus. The Board
Observers shall be provided with the same notice with respect to all meetings
that is provided to the members of the Board of Directors, be entitled to
attend each meeting of the Board of Directors (including executive sessions)
and receive copies of all materials that are distributed to the members of the
Board of Directors. The Board Observers shall not be considered members of the
Board of Directors for any purpose whatsoever and shall not be entitled to vote
on any matters before the Board of Directors or counted for purposes of
determining whether a quorum exists at a meeting of the Board of Directors.

SECTION 5. REMEDIES FOR BREACH

         5.1 General. If any Shareholder under this Agreement fails to give a
notice, make an offer, sell Shares of the Company, close a sale or do any other
act required of such Shareholder under this Agreement, then, if the failure
continues for ten Business Days after notice to the Shareholder in default by
the Company or one of the non-defaulting Shareholders, the Company and such
non-defaulting Shareholders, or any one of them, may institute and maintain a
proceeding to compel the defaulting Shareholder's specific performance of this
Agreement. The remedy of specific performance shall be in addition to any and
all of the remedies at law or in equity including, but not limited to,
injunctive relief and an action for damages, to which any Shareholder of the
Company may be entitled, subject to compliance with Section 7.10 hereof.

         5.2 No Personal Liability. No Shareholder shall have any personal
liability for any debts of the Company that may be created as a result of this
Agreement unless otherwise agreed to in writing by such Shareholder.

SECTION 6. LEGEND ON STOCK CERTIFICATES

         Each Shareholder agrees that the certificates representing Shares
subject to the provisions of this Agreement shall be endorsed as follows:

                  "THE SECURITIES REPRESENTED BY THIS CERTIFICATE HAVE NOT BEEN
                  REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED, OR
                  THE SECURITIES LAWS OF ANY STATE AND MAY NOT BE SOLD OR
                  OTHERWISE DISPOSED OF EXCEPT PURSUANT TO AN EFFECTIVE
                  REGISTRATION STATEMENT UNDER SUCH ACT

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                  AND APPLICABLE STATE SECURITIES LAWS OR PURSUANT TO AN
                  APPLICABLE EXEMPTION TO THE REGISTRATION REQUIREMENTS OF SUCH
                  ACT OR SUCH LAWS.

                  THE SHARES OF STOCK REPRESENTED BY THIS CERTIFICATE ARE
                  SUBJECT TO A SHAREHOLDERS AGREEMENT DATED AS OF MAY 18, 1998,
                  AS AMENDED AND RESTATED NOVEMBER 16, 1999, AND AS MAY BE
                  AMENDED FURTHER FROM TIME TO TIME, AND SAID SHARES MAY NOT BE
                  SOLD, TRANSFERRED, ASSIGNED, HYPOTHECATED OR OTHERWISE
                  DISPOSED OF EXCEPT IN ACCORDANCE WITH THE TERMS OF SUCH
                  AGREEMENT. SUCH AGREEMENT MAY BE EXAMINED AT THE PRINCIPAL
                  PLACE OF BUSINESS OF THE COMPANY AND A COPY THEREOF WILL BE
                  FURNISHED WITHOUT CHARGE TO THE HOLDER OF THIS CERTIFICATE
                  UPON RECEIPT BY THE COMPANY AT ITS PRINCIPAL PLACE OF
                  BUSINESS OR REGISTERED OFFICE OF A WRITTEN REQUEST FROM THE
                  SHAREHOLDER."

SECTION 7. MISCELLANEOUS

         7.1 Modifications and Waivers. This Agreement may not be amended or
modified, nor may the rights of any party be waived, except by a written
document that is executed by the Company, and by two-thirds of the Shares held
by Founders, Investors, and 51% of the Shares held by Holders, each voting as a
class. Notwithstanding the foregoing, additional Holders may become parties to
this Agreement with only the consent of the Company by executing, together with
the Company, a counterpart signature page hereto.

         7.2 Rights and Obligations of Third Parties. Nothing in this
Agreement, whether express or implied, is intended to confer any rights or
remedies under or by reason of this Agreement on any persons other than the
parties to it and their respective successors and permitted assigns, nor is
anything in this Agreement intended to relieve or discharge the obligation or
liability of any third parties to any party to this Agreement, nor shall any
provision give any third party any right of subrogation or action against any
party to this Agreement.

         7.3 Notices. Any notice, request, consent, or other communication
hereunder shall be in writing, and shall be sent by one of the following means:
(a) by registered or certified first class mail, postage prepaid, return
receipt requested; (b) by facsimile transmission with confirmation of receipt;
(c) by overnight courier service; or (d) by personal delivery, and shall be
properly addressed to the Company at its principal offices and to the
Shareholders at the addresses or facsimile numbers set forth in the shareholder
records of the Company. The Company hereby agrees to provide a list of
Shareholders addresses upon written request by any party executing this
Agreement. Notices sent by mail or by courier shall be effective seven days
after they are sent, and notices delivered personally by facsimile shall be
effective at the time of delivery thereof.

                                     -10-
<PAGE>   13

         7.4 Entire Agreement. This Agreement constitutes the entire agreement
between the parties hereto in relation to the subject matter hereof. Any prior
written or oral negotiations, correspondence, or understandings relating to the
subject matter hereof, including the Company's Shareholder Agreement dated as
of February 6, 1998, shall be superseded by this Agreement and shall have no
force or effect.

         7.5 Severability. If any provision that is not essential to the
effectuation of the basic purpose of this Agreement is determined by a court of
competent jurisdiction to be invalid and contrary to any existing or future
law, such invalidity shall not impair the operation of the remaining provisions
of this Agreement.

         7.6 Headings. The headings of the Sections of this Agreement are
inserted for convenience of reference only and shall not affect the
construction or interpretation of any provisions hereof.

         7.7 Counterparts. This Agreement may be executed in any number of
counterparts, each of which when executed and delivered shall be an original,
but all of which together shall constitute one and the same instrument.

         7.8 Governing Law. This Agreement shall be construed in accordance
with and governed by the laws of the State of Colorado.

         7.9 Delays or Omissions. No delay or omission to exercise any right,
power, or remedy accruing to either party, upon any breach or default of the
other party under this Agreement, shall impair any such right, power, or
remedy, nor shall it be construed to be a waiver of any such breach or default,
or an acquiescence therein, or of or in any similar breach of default
thereafter occurring; nor shall any waiver of any single breach or default be
deemed a waiver of any other breach or default theretofore or thereafter
occurring. Any waiver, permit, consent, or approval on the part of either party
of any breach or default by the other party under this Agreement, or any waiver
of any provisions or conditions of this Agreement must be made in writing
signed by the parties and shall be effective only to the extent specifically
set forth in such writing. All remedies, either under this Agreement or by law
or otherwise afforded to either party, shall be cumulative and not alternative.

         7.10 Arbitration. Except as set forth in Section 5.1, the parties
hereby covenant and agree that any legal suit, dispute, claim, demand,
controversy or cause of action of every kind and nature whatsoever, known or
unknown, fixed or contingent, that either a Shareholder or the Company may now
have or at any time in the future claim to have based in whole or in part, or
arising from or out of or that in any way is related to the negotiations,
execution, interpretation or enforcement of this Agreement (collectively, the
"Disputes") shall be completely and finally settled by submission of any such
Disputes to arbitration under the rules of the American Arbitration Association
("AAA") then in effect. There shall be one arbitrator, and such arbitrator
shall be chosen by mutual agreement of the parties in accordance with AAA
rules. Unless the parties agree otherwise, the arbitration proceedings shall
take place in Boulder, Colorado. The arbitrator shall apply Colorado law to all
issues in dispute, in accordance with Section 7.8 above.

                                     -11-
<PAGE>   14

Notice of demand for arbitration shall be filed in writing with the other party
to this Agreement and with the AAA. In no event shall the demand for
arbitration be made after the date when institution of legal or equitable
proceedings based on such Dispute would be barred by the applicable statute of
limitations. The findings of the arbitrator shall be final and binding on the
parties. Judgment on such award may be entered in any court of competent
jurisdiction, or application may be made to that court for a judicial
acceptance of the award and an order or enforcement, as the party seeking to
enforce that award may elect. The prevailing party in any such action shall be
entitled to receive from the losing party all reasonable costs and expenses,
including the reasonable fees of attorneys, accountants, and other experts,
incurred by the prevailing party in investigating and prosecuting (or
defending) such action, together with any such fees which may be incurred in
enforcing any award or judgment.

         7.11 Termination. This Agreement shall terminate upon the earlier of
the following to occur: (a) a Qualifying IPO; (b) the sale of all or
substantially all of the assets of the Company; or (c) the mutual written
consent of each party hereto. Upon such termination, all rights and obligations
of the parties hereto shall terminate. This Agreement shall terminate also as
to any party hereto when such party no longer holds any Shares.

                            [SIGNATURE PAGES FOLLOW]

                                     -12-
<PAGE>   15

         IN WITNESS WHEREOF, the parties have executed this Shareholders
Agreement as of the date first above written.

<TABLE>
<S>                                                           <C>
COMPANY:                                                      INVESTORS:

ARRAY BIOPHARMA, INC., a Delaware                           FRAZIER HEALTHCARE II, L.P.
Corporation

By: /s/ ROBERT CONWAY                                         By: /s/ ALAN D. FRAZIER
   ------------------------------------------                    ------------------------------------------------
   Robert Conway, Chief Executive Officer                     Name:  Alan D. Frazier
                                                                   ----------------------------------------------
                                                              Title: Managing Partner
                                                                    ---------------------------------------------

                                                              ARCH VENTURE FUND III, L.P.

                                                              By:  Arch Venture Partners, LLC, its
                                                                     General Partner
                                                              By: /s/ KEITH L. CRADELL
                                                                 ------------------------------------------------
                                                              Name:  Keith L. Cradell
                                                                   ----------------------------------------------
                                                              Title: Managing Director
                                                                    ---------------------------------------------

                                                              ROVENT II LIMITED PARTNERSHIP

                                                              By:  Advent International Limited
                                                                     Partnership, its General Partner
                                                              By:  Advent International Corporation,
                                                                     its General Partner

                                                              By: /s/ JASON FISHERMAN
                                                                 ------------------------------------------------
                                                              Name:  Jason Fisherman
                                                                   ----------------------------------------------
                                                              Title: V.P.
                                                                    ---------------------------------------------

                                                              MITSUI & CO. (U.S.A.), INC.

                                                              By: /s/ YOICHIRO ENDO
                                                                 ------------------------------------------------
                                                              Name:  Yoichiro Endo
                                                                   ----------------------------------------------
                                                              Title: General Manager
                                                                    ---------------------------------------------

                                                              FALCON TECHNOLOGY PARTNERS, L.P.,
                                                              a Delaware limited partnership

                                                              By: /s/ JAMES L. RATHMANN
                                                                 ------------------------------------------------
                                                                    James L. Rathmann, General Partner
</TABLE>

                                     -13-

<PAGE>   16

<TABLE>
<S>                                                           <C>
                                                              BOULDER VENTURES II, L.P.,
                                                                A DELAWARE LIMITED PARTNERSHIP

                                                              By:  /s/ KYLE LEFKOFF
                                                                   ------------------------------------------------
                                                                   Kyle Lefkoff, General Partner

                                                              BOULDER VENTURES II, (ANNEX) L.P.,
                                                                A DELAWARE LIMITED PARTNERSHIP

                                                              By:    /s/ KYLE LEFKOFF
                                                                   ----------------------------------------------
                                                                   Kyle Lefkoff, General Partner

                                                              THE CARUTHERS FAMILY, L.L.C.

                                                              By: /s/ MARVIN H. CARUTHERS
                                                                  -----------------------------------------------
                                                                  Marvin H. Caruthers, Ph.D., Manager

                                                                  /s/ FRANK A. BONSAL, JR.
                                                                  -----------------------------------------------
                                                                  FRANK A. BONSAL, JR.

                                                                  /s/ RICHARD J. DALY
                                                                  -----------------------------------------------
                                                                  RICHARD J. DALY

                                                                  /s/ MICHAEL CARUTHERS
                                                                  -----------------------------------------------
                                                                  MICHAEL CARUTHERS

                                                                  /s/ CHRISTOPHER D. OZEROFF
                                                                  -----------------------------------------------
                                                                  CHRISTOPHER D. OZEROFF

                                                                  /s/ THERESA KOCH
                                                                  -----------------------------------------------
                                                                  THERESA KOCH

                                                                  /s/ WILLIAM R. ROBERTS
                                                                  -----------------------------------------------
                                                                  WILLIAM R. ROBERTS

                                                              FOUNDERS:

                                                                  /s/ DAVID SNITMAN, PH.D.
                                                                  -----------------------------------------------
                                                                  DAVID SNITMAN, PH.D.

                                                                  /s/ KEVIN KOCH, PH.D.
                                                                  -----------------------------------------------
                                                                  KEVIN KOCH, PH.D.
</TABLE>

                                     -14-
<PAGE>   17

<TABLE>
<S>                                                           <C>
                                                                  /s/ ANTHONY D. PISCOPIO
                                                                  -----------------------------------------------
                                                                  ANTHONY D. PISCOPIO, PH.D.

                                                                  /s/ K.C. NICOLAOU, PH.D.
                                                                  -----------------------------------------------
                                                                  K.C. NICOLAOU, PH.D.

                                                              HOLDERS:

                                                                  /s/ FRANCIS J. BULLOCK
                                                                  -----------------------------------------------
                                                                  FRANCIS J. BULLOCK

                                                                  /s/ JOHN JOSEY
                                                                  -----------------------------------------------
                                                                  JOHN JOSEY

                                                                  /s/ LARRY BURGESS
                                                                  -----------------------------------------------
                                                                  LARRY BURGESS

                                                                  /s/ CHAN KOU HWANG
                                                                  -----------------------------------------------
                                                                  CHAN KOU HWANG
</TABLE>

                                     -15-<PAGE>   1

                                                                   EXHIBIT 10.19

                               FIRST AMENDMENT TO
                   AMENDED AND RESTATED SHAREHOLDERS AGREEMENT

         THIS FIRST AMENDMENT TO AMENDED AND RESTATED SHAREHOLDERS AGREEMENT
(the "Agreement") is made and entered into as of the ___ day of April , 2000, by
and among ARRAY BIOPHARMA INC., a Delaware corporation (the "Company"), each of
those persons listed on the signature pages hereto as either "Investors" or
"Founders" and those certain other holders of the Company's capital stock as may
be identified on the signature pages attached hereto (the "Holders") (the
Investors, Founders and Holders are sometimes referred to collectively as the
"Shareholders").

                                     RECITAL

         WHEREAS, the Company and the Shareholders previously entered into that
certain Amended and Restated Shareholders Agreement, dated as of November 16,
1999 (the "Shareholders Agreement"), and the Company and the Shareholders desire
to amend the Shareholders Agreement as provided herein.

         NOW, THEREFORE, in consideration of the premises and for other good and
valuable consideration, the receipt and sufficiency of which are hereby
acknowledged, the parties hereto agree as follows:

                                    AGREEMENT

         1. Amendment. The Shareholders Agreement shall be amended as follows:

            The following subsection (h) shall be added to Section 3.6:

               (h) any Equity Securities issued in connection with a credit
               facility approved by the Board of Directors.

         2. Interpretation. Except as expressly amended by this Agreement, the
Investor Rights Agreement shall remain in full force and effect without change.

         3 . Counterparts. This Agreement may be executed in any number of
counterparts, each of which when executed and delivered shall be an original,
but all of which together shall constitute one and the same instrument.

                            [SIGNATURE PAGES FOLLOW]

<PAGE>   2

         IN WITNESS WHEREOF, the parties hereto have executed this Agreement as
of the date above first written.

COMPANY:                                      INVESTORS:

ARRAY BIOPHARMA, INC, a Delaware              FRAZIER HEALTHCARE II, L.P.
Corporation

By: /s/ ROBERT CONWAY                         By: /s/ ALAN D. FRAZIER
   ---------------------------------------       -------------------------------
   Robert Conway, Chief Executive Officer     Name: Alan D. Frazier
                                                   -----------------------------
                                              Title: Managing Partner
                                                    ----------------------------

                                              ARCH VENTURE FUND III, L.P.

                                              By: Arch Venture Partners, LLC,
                                                     its General Partner

                                              By:
                                                 -------------------------------
                                              Name:
                                                   -----------------------------
                                              Title:
                                                    ----------------------------

                                              ROVENT II LIMITED PARTNERSHIP

                                              By: Advent International Limited
                                                    Partnership, its General
                                                    Partner
                                              By: Advent International
                                                    Corporation, its General
                                                    Partner

                                              By: /s/ JASON FISHERMAN
                                                 -------------------------------
                                              Name: Jason Fisherman
                                                   -----------------------------
                                              Title: V.P.
                                                    ----------------------------

                                              MITSUI & CO. (U.S.A.), INC.

                                              By: /s/ YOICHIRO ENDO
                                                 -------------------------------
                                              Name: Yoichiro Endo
                                                   -----------------------------
                                              Title: General Manager
                                                    ----------------------------

                                              FALCON TECHNOLOGY PARTNERS, L.P.,
                                              a Delaware limited partnership

                                              By: /s/ JAMES L. RATHMANN
                                                 -------------------------------
                                                 James L. Rathmann, General
                                                    Partner

<PAGE>   3

                                              BOULDER VENTURES II, L.P.,
                                                 A DELAWARE LIMITED PARTNERSHIP

                                              By: /s/ KYLE LEFKOFF
                                                 -------------------------------
                                                 Kyle Lefkoff, General Partner

                                              BOULDER VENTURES II, (ANNEX) L.P.,
                                                 A DELAWARE LIMITED PARTNERSHIP

                                              By: /s/ KYLE LEFKOFF
                                                 -------------------------------
                                                 Kyle Lefkoff, General Partner

                                              THE CARUTHERS FAMILY, L.L.C.

                                              By: /s/ MARVIN H. CARUTHERS
                                                 -------------------------------
                                                 Marvin H. Caruthers, Ph.D.,
                                                    Manager

                                              ----------------------------------
                                              FRANK A. BONSAL, JR.

                                              ----------------------------------
                                              RICHARD J. DALY

                                              /s/ MICHAEL CARRUTHERS
                                              ----------------------------------
                                              MICHAEL CARRUTHERS

                                              ----------------------------------
                                              CHRISTOPHER D. OZEROFF

                                              ----------------------------------
                                              THERESA KOCH

                                              ----------------------------------
                                              WILLIAM R. ROBERTS

                                              ----------------------------------
                                              PATRICIA A. KOCH

<PAGE>   4

                                              ----------------------------------
                                              GRETCHEN K. LUPINACCI

                                              ----------------------------------
                                              ROSEMARIE POCHINTESTA

                                              ----------------------------------
                                              RICHARD POCHINTESTA

                                              ----------------------------------
                                              RICHARD POCHINTESTA, JR.

                                              ----------------------------------
                                              GEOFF CARRUTHERS

                                              ----------------------------------
                                              RICHARD CARRUTHERS

                                              ----------------------------------
                                              KAREN CARRUTHERS

                                              ----------------------------------
                                              ROBERT CARRUTHERS

                                              ----------------------------------
                                              JERI CARRUTHERS

                                              FOUNDERS:

                                              /s/ DAVID SNITMAN
                                              ----------------------------------
                                              DAVID SNITMAN, PH.D.

                                              /s/ KEVIN KOCH
                                              ----------------------------------
                                              KEVIN KOCH, PH.D.

                                              /s/ ANTHONY D. PISCOPIO
                                              ----------------------------------
                                              ANTHONY D. PISCOPIO, PH.D.

<PAGE>   5

                                              /s/ K.C. NICOLAOU
                                              ----------------------------------
                                              K.C. NICOLAOU, PH.D.

                                              HOLDERS:

                                              /s/ FRANCIS J. BULLOCK
                                              ----------------------------------
                                              FRANCIS J. BULLOCK

                                              /s/ JOHN JOSEY
                                              ----------------------------------
                                              JOHN JOSEY

                                              ----------------------------------
                                              LARRY BURGESS

                                              ----------------------------------
                                              CHAN KOU HWANG

                                              ----------------------------------
                                              KEITH L. TIMM

                                              ----------------------------------
                                              CHANG RAO

                                              ----------------------------------
                                              THOMAS J. ZAMBORELLI

                                              ----------------------------------
                                              EILEEN P. JOSEY

                                              ----------------------------------
                                              MARK MUNSON

                                              ----------------------------------
                                              ADAM COOK

<PAGE>   6

                                              ----------------------------------
                                              CONRAD W. HUMMEL

                                              ----------------------------------
                                              JOHN GAUDINO

                                              ----------------------------------
                                              ZACHARY JONES

                                              ----------------------------------
                                              CATHERINE A. TARLETON

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