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                                                                   EXHIBIT 10.12

                               AMENDMENT NO. 1 TO
                      COMPOUND SUPPLY AND LICENSE AGREEMENT

      This Amendment No. 1, dated as of August __, 2000 (the "Effective Date"),
is between ArQule, Inc. ("ArQule"), a Delaware Corporation, and the R.W. Johnson
Pharmaceutical Research Institute ("PRI"), a division of Ortho-McNeil
Pharmaceutical, Inc., a Delaware Corporation.

                                 R E C I T A L S

      WHEREAS, PRI and ArQule entered into a Compound Supply and License
Agreement dated December 15, 1998 (the "Agreement") pursuant to which, among
other things, ArQule supplies PRI with Mapping Array Sets (as defined in the
Agreement);

      WHEREAS, ArQule has developed compound libraries that constitute diverse
subsets of its Mapping Array Sets, which ArQule has named Compass Array Sets (as
defined below);

      WHEREAS, PRI desires to access Compass Array Sets that correspond to
Mapping Array Sets produced by ArQule after June 30, 1999 and thereafter during
the term of the Agreement, and ArQule is willing to furnish PRI with such
Compass Array Sets under the terms and conditions of this Amendment; and

      WHEREAS, PRI and ArQule desire to make certain other revisions to the
Agreement, as specified in this Amendment.

      NOW, THEREFORE, in consideration of the mutual covenants set forth in this
Amendment, PRI and ArQule hereby agree as follows:

1. Definitions. Capitalized terms used in this Amendment and not otherwise
defined herein shall have the meanings ascribed to such terms in the Agreement.

      1.1. Section 1.4 of the Agreement is hereby deleted and replaced with the
following:

                  "ArQule Compound" means a chemical compound provided by
                  ArQule to PRI under this Agreement, and specifically includes
                  all compounds in the Mapping Array Sets and Compass Array
                  Sets provided to PRI under the Mapping Array Program.

      1.2. The following definition is hereby added to the Agreement:

                  "Compass Array(TM) Set" means a set of ArQule Compounds
                  consisting of a diverse subset of each Mapping Array Set
                  produced by ArQule. Each Compass Array Set currently includes
                  at least approximately 12.5% of the total ArQule Compounds in

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            the corresponding Mapping Array Set to represent the chemical
            diversity present in that Mapping Array Set.

2. The following caption, "3.1 Delivery of Array Sets," is hereby added under
the caption, "3. Conduct of Mapping Array Program."

3. Section 3.1. is hereby redesignated Subsection 3.1.2.

4. The following subsection is hereby added to the Agreement:

                  3.1.1. Delivery of Compass Array Sets. ArQule shall furnish
      PRI with approximately 150 microliters of a 10 millimolar solution in DMSO
      of each ArQule Compound that is within the Compass Array Sets
      corresponding to the Mapping Array Sets delivered to PRI from July 1, 1999
      and thereafter during the term of the Agreement. The Compass Array Sets
      are delivered in 96 well microtiter plate format. The ArQule Compounds in
      each Compass Array Set shall have an average purity level of at least
      eighty-five percent (85%) as measured by standard analytical chemistry
      methods used at ArQule. ArQule shall use diligent efforts to deliver to
      PRI the Compass Array Sets as follows:

      (i)   within thirty (30) days after the Effective Date of this Amendment
            for Compass Array Sets corresponding to the Mapping Array Sets
            delivered to PRI from July 1, 1999 through December 31, 1999;

      (ii)  within ninety (90) days after the Effective Date of this Amendment
            for Compass Array Sets corresponding to the Mapping Array Sets
            delivered to PRI from January 1, 2000 through June 30, 2000; and

      (iii) for Compass Array Sets corresponding to Mapping Array Sets delivered
            to PRI after June 30, 2000, within one calendar quarter after PRI
            receives the corresponding Mapping Array Set.

      Except as provided in Section 3.3. below, ArQule shall have no
      obligation to identify the individual ArQule Compounds in the
      Compass Array Sets and PRI shall have no obligation to identify its
      Targets.

5. Section 3.2. is hereby deleted in its entirety and replaced with the
following:

            3.2. Screening of ArQule Compounds. Subject to the terms and
      conditions of this Agreement, ArQule hereby grants PRI and its Affiliates
      a nonexclusive, worldwide license (without the right to sublicense) under
      the ArQule Patent Rights and other rights in ArQule Technology to screen
      the ArQule Compounds in the Compass Array Sets and Mapping Array Sets
      against any Targets within the Screening Field. PRI agrees to use efforts
      consistent with its normal scientific practices to screen the ArQule
      Compounds in

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      the Compass Array Sets and Mapping Array Sets against its Targets in the
      Screening Field.

6. The following sentence is hereby added to the end of Subsection 3.3.1. of the
Agreement:

      "PRI shall confirm its initial screening results for Licensed Compounds
      according to its usual internal procedures prior to confirmation with
      resynthesized compounds pursuant to Subsection 3.3.2. below. Once PRI
      confirms activity for a Licensed Compound, PRI shall disclose to ArQule
      the Target and the level of activity for such Licensed Compound.

7. Subsection 3.3.2. is hereby deleted in its entirety and replaced with the
following:

                  3.3.2. Resynthesized Compounds. If PRI requests resynthesized
      samples of a Licensed Compound, ArQule will supply PRI with a sufficient
      quantity (determined by the Research Committee but not more than 25 mg) of
      the resynthesized Licensed Compound to confirm activity and perform
      secondary assays within twenty-one (21) days from the date requested,
      unless synthesis starting materials are unavailable for such resynthesized
      Active Compound, subject to a maximum of forty (40) such requests in any
      one month. Within ninety (90) days after receiving the resynthesized
      Active Compound from ArQule to confirm activity, subject to extension by
      the Research Committee, PRI shall notify ArQule whether activity is
      confirmed.

8. In Subsection 3.3.3. entitled "Activation of Development Licenses", delete
the first sentence and replace with the following:

      "If PRI does not confirm activity within the ninety-day confirmation
      period for a resynthesized Licensed Compound, or if PRI has no further
      interest in that Licensed Compound for any other reason, the Licensed
      Compound shall revert to ArQule as provided in Section 7.5.

9. The following subsection is hereby added to the Agreement:

      3.3.4. Activity Reports. Within thirty (30) days after the conclusion of
      each calendar quarter, PRI shall furnish ArQule with a report that sets
      forth for each assay type the percentage of Active Compounds identified by
      PRI during that quarter in primary screens and confirmatory screens of
      each Compass Array Set and Mapping Array Set. For purposes of this
      Section, the term "assay type" shall mean a bound receptor, soluble
      receptor, enzyme, or whole cell assay.

10. The parties acknowledge and agree that, in accordance with the provisions of
this Amendment, ArQule has been relieved of its obligation to provide PRI with
confirmation samples as originally set forth in the first sentence of Subsection
3.3.2. of the Agreement and has accepted an obligation to furnish PRI with
Compass Array Sets under paragraph 4 of this Amendment (addition of new
Subsection 3.1.1). Accordingly, the parties further agree that the $350,000
resupply fee referenced in Section 5.2. of the Agreement as an allocation of the
annual delivery fee shall be substituted by a $350,000 service fee under the
same terms for the

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preparation and delivery of the Compass Array Sets pursuant to this Amendment.
This change is merely a change in allocation and does not affect the total
amount of the annual delivery fee or any other payment terms under the
Agreement.

      IN WITNESS WHEREOF, the undersigned have duly executed and delivered this
Amendment No. 1 as a sealed instrument effective as of the date first above
written.

R.W. JOHNSON PHARMACEUTICAL RESEARCH INSTITUTE

By:
   _________________________________________
Name:
Title:

ARQULE, INC.

By:
   _________________________________________
Name:
Title:

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