FIRST AMENDMENT TO AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT

EXHIBIT 4.9

First Amendment to
Amended and Restated Investor Rights Agreement

     This First Amendment to the Amended and Restated Investor Rights Agreement (the “Amendment”) is made effective as of October 31, 2005, and is entered into by and among SGX Pharmaceuticals, Inc., a Delaware corporation, previously known as Structural GenomiX, Inc. (the “Company”), certain holders of the Company’s Series A Preferred Stock (“Series A Preferred”), and certain holders of the Company’s Series B Preferred Stock (“Series B Preferred”) (which parties are hereinafter collectively referred to as the “Original Parties”).

     Whereas, the Original Parties have previously entered into that certain Amended and Restated Investor Rights Agreement, dated April 21, 2005 (the “Investor Rights Agreement”);

     Whereas, the Company, Silicon Valley Bank (“SVB”) and Oxford Finance Corporation (“Oxford”) have entered into a Loan and Security Agreement dated September 16, 2005 (the “Loan Agreement”); and

     Whereas, pursuant to the Loan Agreement, the Company agreed to issue certain warrants to SVB and Oxford and to solicit the requisite consent of the parties to the Investor Rights Agreement to add SVB and Oxford as parties to the Investor Rights Agreement to provide such parties with those certain incidental, or “Piggyback,” registration rights pursuant to and as set forth therein.

     Now, therefore, in consideration of the foregoing premises and the mutual covenants and conditions herein, the parties hereto hereby agree that:

     ““Registrable Securities” means the (a) Common Stock of the Company issued or issuable upon conversion of the Shares; (b) Bridge Converted Common Stock; (c) Common Stock of the Company issued or issuable upon conversion of the Conversion Securities (as those securities are defined in the Convertible Promissory Note issued by the Company to mHoldings Trust (“mHoldings”) dated December 21, 2001 (the “Millennium Note”) (or in the event the Conversion Securities (as those securities are defined in the Millennium Note) consist of the Company’s Common Stock, the Conversion Securities (as those securities are defined in the Millennium Note)); (d) Common Stock of the Company issued or issuable upon conversion of the Warrant Securities (or in the event the Warrant

Securities consist of the Company’s Common Stock, the Warrant Securities), provided, however, that any such shares of Common Stock or Warrant Securities issued upon exercise of the Lender Warrants (or upon conversion of the Warrant Securities issued upon exercise thereof) shall not be deemed Registrable Securities for purposes of Section 2.2 or 2.4 hereof; and (e) Common Stock of the Company issued as (or issuable upon the conversion or exercise of any warrant, right or other security which is issued as) a dividend or other distribution with respect to, or in exchange for or in replacement of, such above-described securities. Notwithstanding the foregoing, Registrable Securities shall not include any securities sold by a person to the public either pursuant to a registration statement or Rule 144 or sold in a private transaction in which the transferor’s rights under Section 2 of this Agreement are not assigned.”

     ““Shares” shall mean (a) the Series A Stock and Series B Stock now held or hereafter acquired by the Investors listed on Exhibit A hereto and their permitted assigns; (b) the Pre-Series B Conversion Preferred Stock held by the Investors listed on Exhibit A hereto and their permitted assigns; (c) the Company securities issuable upon exercise of the Warrant and the Lenders Warrants (the “Warrant Securities”); and (d) the Conversion Securities (as those securities are defined in the Millennium Note) issued pursuant to the Millennium Note to mHoldings (or its permitted assigns).”

     ““Lender Warrants” shall mean those certain warrants issued to Silicon Valley Bank and Oxford Finance Corporation (or their respective permitted assigns) pursuant to that certain Loan and Security Agreement dated as of September 16, 2005 by and among the Company, Silicon Valley Bank and Oxford Finance Corporation.”

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Company:

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.