Co-crystal Structure of LATS2 Kinase with Kinase Inhibitor AT-7867

Title: Co-crystal structure of LATS2 Kinase with kinase inhibitor AT-7867 (i) This is a combined synopsis/solicitation for commercial items prepared in accordance with the format in Subpart 12.6 as supplemented with additional information included in this notice. This announcement constitutes the only solicitation; proposals are being requested and a written solicitation will not be issued. (ii) The solicitation number is HHS-NIH-NIDA-CSS-2018-90 and the solicitation is issued as a Request for Quotes (RFQ). This acquisition is for a commercial item or service and is conducted under the authority of the Federal Acquisition Regulation (FAR) Part 13-Simplified Acquisition Procedures; FAR Subpart 13.5-Simplified Procedures for Certain Commercial Items; and FAR Part 12-Acquisition of Commercial Items and is not expected to exceed the simplified acquisition threshold. (iii) The solicitation document and incorporated provisions and clauses are those in effect through Federal Acquisition Circular 2005-96, dated 11/06/2017. (iv) The associated NAICS code 541380 and the small business size standard $15.0M per year. This requirement is competed using full and open procedures with no set-aside restrictions. (v) 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: The purpose of this requirement is to determine 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: Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to perform the Statement of Work. Specifically, the Contractor will: a) Conduct gene template synthesis necessary to support the production of LATS2 protein constructs. b) Produce up to 15 LATS2 protein constructs of varying length in E. coli and baculovirus expression systems. c) Conduct pilot expression and purification studies to evaluate the potential of each construct. d) Scale up the expression and purification of the most promising 1 - 3 constructs in E. coli and baculovirus. e) Conduct co-crystallization experiments using LATS2 kinase and the known small molecule inhibitor AT-7867. f) Obtain an X-ray co-crystal structure of LATS2 kinase and AT-7867 with resolution <3.0 angstroms. g) Provide a comprehensive data report including the structure and all relevant data parameters. (vi) The period of performance is 40 weeks after receipt of award. (vii) The provision at FAR clause 52.212-1, Instructions to Offerors - Commercial Items, applies to this acquisition. (viii) The provision at FAR clause 52.212-2, Evaluation - Commercial Items, applies to this acquisition. a) The Government will award a contract resulting from this solicitation to the responsible offeror whose offer conforming to the solicitation will be most advantageous to the Government. The following factors shall be used to evaluate offers: 1) Technical Capability. The Government will evaluate: - 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). 2) Price Technical capability is significantly more important than price. b) A written notice of award or acceptance of an offer, mailed or otherwise furnished to the successful offeror within the time for acceptance specified in the offer, shall result in a binding contract without further action by either party. Before the offer's specified expiration time, the Government may accept an offer (or part of an offer), whether there are negotiations after its receipt, unless a written notice of withdrawal is received before award. (ix) The Offerors to include a completed copy of the provision at FAR clause 52.212-3, Offeror Representations and Certifications-Commercial Items, with its offer. (x) The FAR clause at 52.212-4, Contract Terms and Conditions - Commercial Items, applies to this acquisition. (xi) FAR clause at 52.212-5, Contract Terms and Conditions Required to Implement Statutes or Executive Orders-Commercial Items, applies to this acquisition. (xii) The Defense Priorities and Allocations System (DPAS) are not applicable to this requirement. (xiii) Responses to this solicitation must include clear and convincing evidence of the offeror's capability of fulfilling the requirement as it relates to the technical evaluation criteria. The price proposal must include the labor categories, an estimate of the number of hours required for each labor category, fully loaded fixed hourly rate or each labor category, breakdown and rationale for other direct costs or materials, and the total amount. In addition the Dun & Bradstreet Number (DUNS), the Taxpayer Identification Number (TIN), and the certification of business size must be included in the response. All offerors must have an active registration in the System for Award Management (SAM) www.sam.gov." All responses must be received by 12:00 PM Eastern, Thursday, February 8, 2018 and reference number HHS-NIH-NIDA-CSS-2018-90. Responses may be submitted electronically to Jeffrey Schmidt, contact@example.gov. Fax responses will not be accepted. (xiv) The name and telephone number of the individual to contact for information regarding the solicitation: Jeffrey Schmidt, +1 (555) 000-0000.