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                                                                   Exhibit 10.46

                                 PROMISSORY NOTE


$62,000.00                                                 San Diego, California
                                                                     May 8, 1998

        FOR VALUE RECEIVED, the undersigned hereby unconditionally promises to
pay to the order of SIGNAL PHARMACEUTICALS, INC., a California corporation (the
"Company"), at 5555 Oberlin Drive, San Diego, California 92121, or at such other
place as the holder hereof may designate in writing, in lawful money of the
United States of America and in immediately available funds, the principal sum
of Sixty-Two Thousand Dollars ($62,000.00) together with interest accrued from
the date hereof on the unpaid principal at the rate of 5.69% per annum, or the
maximum rate permissible by law (which under the laws of the State of California
shall be deemed to be the laws relating to permissible rates of interest on
commercial loans), whichever is less, as follows:

                PRINCIPAL REPAYMENT. The outstanding principal amount hereunder
        shall be due and payable in full on May 8, 2003.

                INTEREST PAYMENTS. Interest shall be payable annually in arrears
        and shall be calculated on the basis of a 360-day year for the actual
        number of days elapsed;

provided, however, that in the event that the undersigned's employment by or
association with the Company is terminated for any reason prior to payment in
full of this Note, this Note shall be accelerated and all remaining unpaid
principal and interest shall become due and payable ninety (90) days after such
termination.

        If the undersigned fails to pay any of the principal and accrued
interest when due, the Company, at its sole option, shall have the right to
accelerate this Note, in which event the entire principal balance and all
accrued interest shall become immediately due and payable, and immediately
collectible by the Company pursuant to applicable law.

        This Note may be prepaid at any time without penalty. All money paid
toward the satisfaction of this Note shall be applied first to the payment of
interest as required hereunder and then to the retirement of the principal.

        The full amount of this Note is secured by a pledge of shares of Common
Stock of the Company (the "Pledged Shares"), and is subject to all of the terms
and provisions of the Stock Purchase Agreement and the Stock Pledge Agreement,
each of even date herewith between the undersigned and the Company.

        If the undersigned sells or transfers any of the Pledged Shares (whether
or not such sale or transfer is for consideration or for no consideration), this
Note shall be accelerated and all remaining unpaid principal and interest shall
become immediately due and payable after such sale or transfer.


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        The undersigned hereby represents and agrees that the amounts due under
this Note are not consumer debt, and are not incurred primarily for personal,
family or household purposes, but are for business and commercial purposes only.

        The undersigned hereby waives presentment, protest and notice of
protest, demand for payment, notice of dishonor and all other notices or demands
in connection with the delivery, acceptance, performance, default or endorsement
of this Note.

        The holder hereof shall be entitled to recover, and the undersigned
agrees to pay when incurred, all costs and expenses of collection of this Note,
including without limitation, reasonable attorneys' fees.

        This Note shall be governed by, and construed, enforced and interpreted
in accordance with, the laws of the State of California, excluding conflict of
laws principles that would cause the application of laws of any other
jurisdiction.


                                     Signed    /s/ ALAN J. LEWIS, PH.D.
                                            ------------------------------------
                                                  ALAN J. LEWIS, PH.D.


EXHIBIT A - Stock Pledge Agreement


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                                    EXHIBIT A

                             STOCK PLEDGE AGREEMENT


        THIS STOCK PLEDGE AGREEMENT ("Pledge Agreement") is made by ALAN J.
LEWIS PH.D., an individual residing at 6510 Monte Fuego, Rancho Santa Fe,
California 92067 ("Pledgor"), in favor of SIGNAL PHARMACEUTICALS, INC., a
California corporation with its principal place of business at 5555 Oberlin
Drive, San Diego, California 92121 ("Pledgee").

        WHEREAS, Pledgor has concurrently herewith executed that certain
Promissory Note (the "Note") in favor of Pledgee in the amount of Sixty-Two
Thousand Dollars ($62,000.00) in payment of the purchase price of Four Hundred
Twenty-Five Thousand (425,000) shares of the Common Stock of Pledgee; and

        WHEREAS, Pledgee is willing to accept the Note from Pledgor, but only
upon the condition, among others, that Pledgor shall have executed and delivered
to Pledgee this Pledge Agreement and the Collateral (as defined below):

        NOW, THEREFORE, in consideration of the foregoing recitals and for other
good and valuable consideration, the receipt and adequacy of which are hereby
acknowledged, and intending to be legally bound, Pledgor hereby agrees as
follows:

        1. As security for the full, prompt and complete payment and performance
when due (whether by stated maturity, by acceleration or otherwise) of all
indebtedness of Pledgor to Pledgee created under the Note (all such indebtedness
being the "Liabilities"), together with, without limitation, the prompt payment
of all expenses, including, without limitation, reasonable attorneys' fees and
legal expenses, incidental to the collection of the Liabilities and the
enforcement or protection of Pledgee's lien in and to the collateral pledged
hereunder, Pledgor hereby pledges to Pledgee, and grants to Pledgee, a first
priority security interest in all of the following (collectively, the "Pledged
Collateral"):

               (a) Four Hundred Twenty-Five Thousand (425,000) shares of Common
Stock of Pledgee represented by Certificate No.(s) ____________ (the "Pledged
Shares"), and all dividends, cash, instruments, and other property or proceeds
from time to time received, receivable, or otherwise distributed in respect of
or in exchange for any or all of the Pledged Shares;

                (b) all voting trust certificates held by Pledgor evidencing the
right to vote any Pledged Shares subject to any voting trust; and

                (c) all additional shares and voting trust certificates from
time to time acquired by Pledgor in any manner (which additional shares shall be
deemed to be part of the Pledged Shares), and the certificates representing such
additional shares, and all dividends, cash, instruments, and other property or
proceeds from time to time received, receivable, or otherwise distributed in
respect of or in exchange for any or all of such shares.


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        The term "indebtedness" is used herein in its most comprehensive sense
and includes any and all advances, debts, obligations and Liabilities
heretofore, now or hereafter made, incurred or created, whether voluntary or
involuntary and whether due or not due, absolute or contingent, liquidated or
unliquidated, determined or undetermined, and whether recovery upon such
indebtedness may be or hereafter becomes unenforceable.

        2. At any time, without notice, and at the expense of Pledgor, Pledgee
in its name or in the name of its nominee or of Pledgor may, but shall not be
obligated to: (i) collect by legal proceedings or otherwise all dividends
(except cash dividends other than liquidating dividends), interest, principal
payments and other sums now or hereafter payable upon or on account of said
Pledged Collateral; (ii) enter into any extension, reorganization, deposit,
merger or consolidation agreement, or any agreement in any wise relating to or
affecting the Pledged Collateral, and in connection therewith may deposit or
surrender control of such Pledged Collateral thereunder, accept other property
in exchange for such Pledged Collateral and do and perform such acts and things
as it may deem proper, and any money or property received in exchange for such
Pledged Collateral shall be applied to the indebtedness or thereafter held by it
pursuant to the provisions hereof; (iii) insure, process and preserve the
Pledged Collateral; (iv) cause the Pledged Collateral to be transferred to its
name or to the name of its nominee; or (v) exercise as to such Pledged
Collateral all the rights, powers and remedies of an owner, except that so long
as no default exists under the Note or hereunder Pledgor shall retain all voting
rights as to the Pledged Shares.

        3. Pledgor agrees to pay prior to delinquency all taxes, charges, liens
and assessments against the Pledged Collateral, and upon the failure of Pledgor
to do so, Pledgee at its option may pay any of them and shall be the sole judge
of the legality or validity thereof and the amount necessary to discharge the
same.

        4. At the option of Pledgee and without necessity of demand or notice,
all or any part of the indebtedness of Pledgor shall immediately become due and
payable irrespective of any agreed maturity, upon the happening of any of the
following events: (i) failure to keep or perform any of the terms or provisions
of this Pledge Agreement; (ii) failure to pay any installment of principal or
interest on the Note when due; (iii) the levy of any attachment, execution or
other process against the Pledged Collateral; or (iv) the insolvency, commission
of an act of bankruptcy, general assignment for the benefit of creditors, filing
of any petition in bankruptcy or for relief under the provisions of Title 11 of
the United States Code of, by, or against Pledgor.

        5. In the event of the nonpayment of any indebtedness when due, whether
by acceleration or otherwise, or upon the happening of any of the events
specified in the last preceding paragraph, Pledgee may then, or at any time
thereafter, at its election, apply, set off, collect or sell in one or more
sales, or take such steps as may be necessary to liquidate and reduce to cash in
the hands of Pledgee in whole or in part, with or without any previous demands
or demand of performance or notice or advertisement, the whole or any part of
the Pledged Collateral in such order as Pledgee may elect, and any such sale may
be made either at public or private sale at its place of business or elsewhere,
or at any broker's board or securities exchange, either for cash or upon credit
or for future delivery; provided, however, that if such disposition is


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at private sale, then the purchase price of the Pledged Collateral shall be
equal to the public market price then in effect, or, if at the time of sale no
public market for the Pledged Collateral exists, then, in recognition of the
fact that the sale of the Pledged Collateral would have to be registered under
the Securities Act of 1933 and that the expenses of such registration are
commercially unreasonable for the type and amount of collateral pledged
hereunder, Pledgee and Pledgor hereby agree that such private sale shall be at a
purchase price mutually agreed to by Pledgee and Pledgor or, if the parties
cannot agree upon a purchase price, then at a purchase price established by a
majority of three independent appraisers knowledgeable of the value of such
collateral, one named by Pledgor within 10 days after written request by the
Pledgee to do so, one named by Pledgee within such 10 day period, and the third
named by the two appraisers so selected, with the appraisal to be rendered by
such body within 30 days of the appointment of the third appraiser. The cost of
such appraisal, including all appraiser's fees, shall be charged against the
proceeds of sale as an expense of such sale. Pledgee may be the purchaser of any
or all Pledged Collateral so sold and hold the same thereafter in its own right
free from any claim of Pledgor or right of redemption. Demands of performance,
notices of sale, advertisements and presence of property at sale are hereby
waived, and Pledgee is hereby authorized to sell hereunder any evidence of debt
pledged to it. Any sale hereunder may be conducted by any officer or agent of
Pledgee.

        6. The proceeds of the sale of any of the Pledged Collateral and all
sums received or collected by Pledgee from or on account of such Pledged
Collateral shall be applied by Pledgee to the payment of expenses incurred or
paid by Pledgee in connection with any sale, transfer or delivery of the Pledged
Collateral, to the payment of any other costs, charges, attorneys' fees or
expenses mentioned herein, and to the payment of the indebtedness or any part
hereof, all in such order and manner as Pledgee in its discretion may determine.
Pledgee shall then pay any balance to Pledgor.

        7. Upon the transfer of all or any part of the indebtedness Pledgee may
transfer all or any part of the Pledged Collateral and shall be fully discharged
thereafter from all liability and responsibility with respect to such Pledged
Collateral so transferred, and the transferee shall be vested with all the
rights and powers of Pledgee hereunder with respect to such Pledged Collateral
so transferred; but with respect to any Pledged Collateral not so transferred
Pledgee shall retain all rights and powers hereby given.

        8. Until all indebtedness shall have been paid in full the power of sale
and all other rights, powers and remedies granted to Pledgee hereunder shall
continue to exist and may be exercised by Pledgee at any time and from time to
time irrespective of the fact that the indebtedness or any part thereof may have
become barred by any statute of limitations, or that the personal liability of
Pledgor may have ceased.

        9. Pledgee agrees that so long as no default exists under the Note or
hereunder, the Pledged Shares shall, upon the request of Pledgor, be released
from pledge as the indebtedness is paid. Such releases shall be at the rate of
one share for each fourteen cents ($0.14) of principal amount of indebtedness
paid. Release from pledge, however, shall not result in release from the


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provisions of those certain Joint Escrow Instructions, if any, of even date
herewith among the parties to this Pledge Agreement and the Escrow Agent named
therein.

        10. Pledgee may at any time deliver the Pledged Collateral or any part
thereof to Pledgor and the receipt of Pledgor shall be a complete and full
acquittance for the Pledged Collateral so delivered, and Pledgee shall
thereafter be discharged from any liability or responsibility therefor.

        11. The rights, powers and remedies given to Pledgee by this Pledge
Agreement shall be in addition to all rights, powers and remedies given to
Pledgee by virtue of any statute or rule of law. Any forbearance or failure or
delay by Pledgee in exercising any right, power or remedy hereunder shall not be
deemed to be a waiver of such right, power or remedy, and any single or partial
exercise of any right, power or remedy hereunder shall not preclude the further
exercise thereof; and every right, power and remedy of Pledgee shall continue in
full force and effect until such right, power or remedy is specifically waived
by an instrument in writing executed by Pledgee.

        12. If any provision of this Pledge Agreement is held to be
unenforceable for any reason, it shall be adjusted, if possible, rather than
voided in order to achieve the intent of the parties to the extent possible. In
any event, all other provisions of this Pledge Agreement shall be deemed valid
and enforceable to the full extent possible.

        13. This Pledge Agreement shall be governed by, and construed in
accordance with, the laws of the State of California as applied to contracts
made and performed entirely within the State of California by residents of such
State. Dated: May 8, 1998

PLEDGOR



 /s/ ALAN J. LEWIS, Ph.D.
-------------------------------
ALAN J. LEWIS, Ph.D.



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