The scope of this MCSP task order shall be medicinal chemistry services under Performance Area 2: Medicinal Chemistry Support in support of preclinical drug discovery efforts supported by NIH, NINDS and its Contributors including: Medicinal Chemistry Planning, Synthesis, Isolation, Characterization 1) Project planning 2) Project management 3) Design, procurement, and milligram-scale synthesis of chemical analogs 4) Multi-gram and scale-up synthesis for testing in animal models 5) In vitro ADME and toxicology testing for lead optimization 6) Compound registration and data entry 7) Communication (teleconferences, minutes, written updates) In addition to the specific technical requirements specified below, the Contractor shall fulfill the general technical requirements defined in the Parent Statement of Work, “Performance Area 2 Medicinal Chemistry Support”, which states the general technical requirements for this solicitation. The SOW consists of three components: the Base Requirement: Exploratory Chemistry; Option #1 Hit-to-Lead Chemistry; and Option #2 Lead Optimization Chemistry. Base Award: Exploratory Chemistry The goal of Exploratory Chemistry is to gather sufficient data to determine whether the starting compound(s) and primary bioactivity assay provided by the Contributor are suitable for pursuing Hit-toLead Chemistry. In order to initiate a Hit-to-Lead effort, compound(s) typically should elicit a reproducible dose response, demonstrate a potency of IC50/EC50 < 10 µM (preferably < 1 µM) with at least 10x selectivity in counterscreens, demonstrate an emerging structure-activity relationship (SAR) across related chemical analogs, and provide a tractable starting point for optimization. It is expected that this Exploratory Chemistry effort will have a duration of approximately eight (8) months and will require all components including synthesis, Computer Aided Drug Design (CADD) as appropriate, and in vitro ADMET support (as outlined in the Parent SOW). General Requirements of Exploratory Chemistry Task Orders: The Contractor, the Contributor, and the Contracting Officer’s Representative (COR) shall communicate on a regular basis over the course of an Exploratory Chemistry project to review data and refine the testing strategy as described above. It is recognized that the resource requirements both in terms of staffing and timing may vary from program to program. The Contractor shall procure and provide each Contributor with samples for testing in their bioactivity assay(s). The Contractor shall be responsible for maintaining a repository of the compounds synthesized or purchased by the Contractor for each of the Contributor’s projects. The Contributor shall be responsible for testing the commercial and custom-designed analogs in their bioactivity assay(s) and entering the bioactivity data into an NIH database that will be accessible to the Contractor. The Exploratory phase of a project will end when the COR determines that sufficient data i...