SOURCES SOUGHT
Q -- Co-crystal Structure of LATS2 Kinase with Kinase Inhibitor AT-7867
- Notice Date
- 1/17/2018
- Notice Type
- Sources Sought
- NAICS
- 541380
— Testing Laboratories
- Contracting Office
- Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse, 6001 Executive Boulevard, Room 4211, MSC 9559, Bethesda, Maryland, 20892-9559, United States
- ZIP Code
- 20892-9559
- Solicitation Number
- HHS-NIH-NIDA-SBSS-2018-65
- Archive Date
- 2/8/2018
- Point of Contact
- Jeffrey Schmidt, Phone: (301) 402-1488
- E-Mail Address
-
schmidtjr@mail.nih.gov
(schmidtjr@mail.nih.gov)
- Small Business Set-Aside
- N/A
- Description
- This is a Small Business Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding: (1) the availability and capability of qualified small business sources; (2) whether they are small businesses; HUBZone small businesses; service-disabled, veteran-owned small businesses; 8(a) small businesses; veteran-owned small businesses; woman-owned small businesses; or small disadvantaged businesses; and (3) their size classification relative to the North American Industry Classification System (NAICS) code for the proposed acquisition. Your responses to the information requested will assist the Government in determining the appropriate acquisition method, including whether a set-aside is possible. An organization that is not considered a small business under the applicable NAICS code should not submit a response to this notice. This notice is issued to help determine the availability of qualified companies technically capable of meeting the Government requirement and to determine the method of acquisition. It is not to be construed as a commitment by the Government to issue a solicitation or ultimately award a contract. Responses will not be considered as proposals or quotes. No award will be made as a result of this notice. The Government will NOT be responsible for any costs incurred by the respondents to this notice. This notice is strictly for research and information purposes only. Background: The National Institutes of Health (NIH) is the nation's leading medical research agency and the primary Federal agency whose mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability, conducting, supporting and making medical discoveries that improve people's health and save lives. The National Center for Advancing Translational Sciences (NCATS) is a translational science center that prides itself on its tremendously productive pipeline and is innovative in a number of ways. NCATS brings together a diverse range of scientists, including medicinal chemists, biologists, toxicologists, and engineers, in order to ultimately translate basic science into real products and services that help improve people's lives. Included in this process is the development of unique small molecules as potential anticancer agents. The repurposing of known drugs for use against novel targets is a validated method for accelerating translational drug discovery. NCATS has an ongoing program aimed at the repurposing of such drugs, specifically including kinase inhibitors, which typically inhibit not only the original kinase target, but also other kinases of interest. We have tested a collection of known kinase inhibitor drugs against a broad panel of kinases, and from that determined that the known inhibitor AT-7867 potently inhibits LATS2, an emerging kinase of great interest in the biomedical community. Data from recent publications highlight an important role for LATS2 in tumor suppression as part of the Hippo signaling pathway. Potent and selective inhibitors of LATS2 have not yet been reported in the literature, and would be highly useful as tools for further elucidating the role of LATS2, and as starting points for LATS2 inhibitor drugs. The determination of an X-ray co-crystal structure of LATS2 kinase bound to AT-7867 will facilitate the rapid repurposing of AT-7867 and analogs thereof as inhibitors of the novel kinase LATS2. These would be useful both as tools for further elucidating the important biology associated with LATS2, and as potential starting points for developing LATS2 inhibitor drugs. Purpose and Objectives: This order provides for determination of an X-ray co-crystal structure of LATS2 kinase with a known potent inhibitor of LATS2 (AT-7867). This determination will provide a starting point for the potential repurposing of AT-7867 and subsequent analogs as inhibitors of this novel kinase. Project requirements: The Contractor will be required to: •Conduct gene template synthesis necessary to support the production of LATS2 protein constructs. •Produce up to 15 LATS2 protein constructs of varying length in E. coli and baculovirus expression systems. •Conduct pilot expression and purification studies to evaluate the potential of each construct. •Scale up the expression and purification of the most promising 1 - 3 constructs in E. coli and baculovirus. •Conduct co-crystallization experiments using LATS2 kinase and the known small molecule inhibitor AT-7867. •Obtain an X-ray co-crystal structure of LATS2 kinase and AT-7867 with resolution <3.0 angstroms. •Provide a comprehensive data report including the structure and all relevant data parameters. Anticipated period of performance: The Contractor will be given 40 weeks to complete the project requriements. Other important considerations: The Government will solicit this requirement using trade-off evaluation procedures. The Government will evaluate contractor: •Experience in the production of proteion constructs protein constructs using E. coli and baculovirus expression systems, including SF9, SF21 and High V cells. •Protein production capacity in E. coli (>200 L / week) and in baculovirus systems (>50 L / week). •Experience in the determination of X-ray co-crystal structures of proteins with small molecule inhibitors. •Access to all critical instrumentation necessary to accomplish the project requirements, including access to a high-quality synchrotron such as the Chicago Advanced Photon Source (APS) or the Shanghai Synchrotron Radiation Facility (SSRF). Capability statement /information sought: Small Businesses that believe they possess the ability to satisfy the project requirements should submit capability statements. Capability statements hould include the following •Respondents' opinions about the difficulty and/or feasibility of the potential requirement or proposed acquisition, possible solutions and approaches that may currently exist in the marketplace, and information regarding innovative ideas or concepts. •Information regarding respondents': (a) staff expertise, including their availability, experience, and formal and other training; (b) current in-house capability and capacity to perform the work; (c) prior completed projects of similar nature; (d) corporate experience and management capability; and (e) examples of prior completed Government contracts, references, and other related information. The respondent must also provide their DUNS number, organization name, address, point of contact, and size and type of business (e.g., 8(a), HubZone, etc., pursuant to the applicable NAICS code and any other information that may be helpful in developing or finalizing the acquisition requirements. One (1) copy of the response is required and must be in Microsoft Word or Adobe PDF format using 11-point or 12-point font, 8-1/2" x 11" paper size, with 1" top, bottom, left and right margins, and with single or double spacing. The information submitted must be must be in and outline format that addresses each of the elements of the project requirement and in the capability statement /information sought paragraphs stated herein. A cover page and an executive summary may be included but is not required. The response is limited to ten (10) page limit. The 10-page limit does not include the cover page, executive summary, or references, if requested. The response must include the respondents' technical and administrative points of contact, including names, titles, addresses, telephone and fax numbers, and e-mail addresses. All responses to this notice must be submitted electronically to the Contract Specialist and Contracting Officer. Facsimile responses are NOT accepted. The response must be submitted to Jeffrey Schmidt, Contracting Officer, at e-mail address schmidtjr@mail.nih.gov. The response must be received on or before January 24, 2018, 12:00 PM Eastern Time. Disclaimer and Important Notes: This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization's qualifications to perform the work. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After a review of the responses received, a presolicitation synopsis and solicitation may be published in Federal Business Opportunities. However, responses to this notice will not be considered adequate responses to a solicitation. Confidentiality: No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s)."
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