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                                                                  EXHIBIT 10.133


                          FIFTH AMENDMENT TO AGREEMENT

            This is the fifth amendment to the Research Collaboration and
License Agreement between MERCK & CO., INC., a corporation organized and
existing under the laws of New Jersey ("MERCK") and ARRIS PHARMACEUTICAL
CORPORATION, a corporation organized and existing under the laws of Delaware,
now known as Axys Pharmaceuticals, Inc- ("Axys") made as of November 6, 1996
(the "Agreement"). The purpose of this fifth amendment is to extend the research
term of the collaboration through November 5, 2001.

            1. In accordance with the provisions of Section 2.8 and Section
5.2(d) of the Agreement and subject to MERCK's right to terminate the Research
Program and the Agreement in accordance with Section 8.2, the Research Program
Term is extended through November 5, 2001 and the parties agree that eleven (11)
FTEs will be required during the period November 6, 2000 through November 5,
2001 payable at an annual rate of         **         per FTE.

            2. Attachment 2.1 setting forth the Research Program is hereby
amended to include the additional work set forth in the attachment to this fifth
amendment.

            3. Capitalized terms used and not otherwise defined herein shall
have the respective meanings set forth in the Agreement. The Agreement, together
with the first amendment dated February 9, 1998, the second amendment dated
November 5, 1998, the third amendment dated November 18, 1999, the fourth
amendment dated March 3, 2000 and this fifth amendment contain the entire
understanding of the parties with respect to their subject matter. All express
or implied agreements and understandings, either oral or written, heretofore
made are expressly merged in and made a part of the Agreement as amended by the
first, second, third, fourth and fifth amendments. All other terms and
conditions of the Agreement, as amended, continue in full force and effect. The
Agreement and its amendments may be amended, or any term thereof modified, only
by a written instrument duly executed by both parties hereto.

            IN WITNESS WHEREOF, the parties have entered into this Amendment as
of November, 2000.

<TABLE>
<CAPTION>
MERCK & CO., INC.                           AXYS PHARMACEUTICALS, INC.
<S>                                         <C>
BY:                                         BY: /s/ MICHAEL C. VENUTI  11/6/00
    ------------------------------              ------------------------------
                                                Michael C. Venuti, Ph.D.
                                                Sr. VP Research, Chief Technical
                                                Officer

</TABLE>

* Confidential treatment has been requested by the Registrant.

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                                 ATTACHMENT 2.1

                                RESEARCH PROGRAM

The work outlined below, initiated during Q-IV 2000, and completed by November
5, 2001.

1.    Enzymology

      Axys will support its internal chemistry effort and primary enzyme assay
      screens to develop Active Compounds and to evaluate their specificity
      versus human         **         and       **       as well as cathepsins
              **        as required for specific compounds and studies. Merck
      will continue to perform HTS assays on the Merck sample collection at the
      designated Merck site. An Active Compound will be characterized and
      considered for further optimization towards identification of a Safety
      Assessment Candidate as defined by Merck in its sole discretion in year
      2001 subject to bone safety proof of concept validation in rabbits by
      Merck in 3Q01

      **

3.    X-ray Crystallography

      Axys will supply to Merck the currently available high resolution crystal
      structures and coordinates and documentation relating to the recombinant
      human CatK-inhibitor complexes or humanized rabbit CatK-inhibitor
      complexes. Axys will provide to Merck the unpublished coordinates of all
      solved CatK, CatL, CatK-inhibitor complexes, and CatL-inhibitor complexes.

4.    Cell Biology/Immunology

NONE

5.    Molecular Biology

NONE

* Confidential treatment has been requested by the Registrant.


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                                                                  Attachment 2.1
                                                                Research Program

6.    Medicinal Chemistry

      With direct guidance from the designated Merck site, Axys and Merck will
      work to develop Program Compound. Axys and Merck will work together to
      deliver an Active Compound which will be characterized and further
      optimized towards identification of an additional Safety Assessment
      Candidate (SAC) as defined by Merck in its sole discretion in year 2001.
      The compound will be orally active and         **         fold selective
      versus other cathepsins and efficacious in         **         and
      **         model and otherwise meet the standard criteria as determined by
      Merck of a SAC. 4Q01.

      **

      **

      **

      **

      **

* Confidential treatment has been requested by the Registrant.


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                                                                  Attachment 2.1
                                                                Research Program

                                   APPENDIX A

        **


* Confidential treatment has been requested by the Registrant.



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                                                                  Attachment 2.1
                                                                Research Program

                                   APPENDIX B

        **

* Confidential treatment has been requested by the Registrant.




                                       4
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                                                                  Attachment 2.1
                                                                Research Program

                                   APPENDIX C

        **


* Confidential treatment has been requested by the Registrant.



                                       5
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                                                                  Attachment 2.1
                                                                Research Program

                                   APPENDIX D

        **

* Confidential treatment has been requested by the Registrant.















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