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                                                                     EXHIBIT 4.1

                            1999 STOCK INCENTIVE PLAN

         The 1999 Stock Incentive Plan (the "1999 Plan") of Texas Biotechnology
Corporation (the "Company") is hereby amended as follows effective March 13,
2001.

         1.       The first paragraph of Section 1.4 is amended to read as
                  follows in its entirety:

                  Subject to adjustment under Section 5.5, there shall be
         available for Incentive Awards under the Plan that are granted wholly
         or partly in Common Stock (including rights or Stock Options that may
         be exercised for or settled in Common Stock) Three Million (3,000,000)
         Shares of Common Stock. Three Million (3,000,000) of the Shares
         reserved under the Plan shall be available for grants of Incentive
         Stock Options. The number of Shares of Common Stock that are the
         subject of Incentive Awards under this Plan, that are forfeited or
         terminated, expire unexercised, are settled in cash in lieu of Common
         Stock or in a manner such that all or some of the Shares covered by an
         Incentive Award are not issued to a Grantee or are exchanged for
         Incentive Awards that do not involve Common Stock, shall again
         immediately become available for Incentive Awards hereunder. The
         Committee may from time to time adopt and observe such procedures
         concerning the counting of Shares against the Plan maximum as it may
         deem appropriate. The Board and the appropriate officers of the Company
         shall from time to time take whatever actions are necessary to file any
         required documents with governmental authorities, stock exchanges and
         transaction reporting systems to ensure that Shares are available for
         issuance pursuant to Incentive Awards.

                  During such period that the Company is a Publicly Held
         Corporation, then unless and until the Committee determines that a
         particular Incentive Award granted to a Covered Employee is not
         intended to comply with the Performance-Based Exception, the following
         rules shall apply to grants of Incentive Awards to Covered Employees:

                           (a) Subject to adjustment as provided in Section 5.5,
                  the maximum aggregate number of Shares of Common Stock
                  (including Stock Options, Restricted Stock, or Other
                  Stock-Based Awards paid out in Shares) that may be granted or
                  that may vest, as applicable, in any calendar year pursuant to
                  any Incentive Award held by any individual Covered Employee
                  shall be 3,000,000 Shares.

                           (b) The maximum aggregate cash payout (including
                  Other Stock-Based Awards paid out in cash) with respect to
                  Incentive Awards granted in any calendar year which may be
                  made to any Covered Employee shall be Ten Million dollars
                  ($10,000,000).

                           (c) With respect to any Stock Option granted to a
                  Covered Employee that is canceled or repriced, the number of
                  Shares subject to such Stock Option shall continue to count
                  against the maximum number of Shares that may be the subject
                  of Stock Options granted to such Covered Employee hereunder
                  and, in this regard, such maximum number shall be determined
                  in accordance with Section 162(m) of the Code.

                           (d) The limitations of subsections (a), (b) and (c)
                  above shall be construed and administered so as to comply with
                  the Performance-Based Exception.