The Contraception Research Branch (CRB) within the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) supports research to develop compounds that can disrupt oogenesis, spermatogenesis, ovulation, sperm maturation and/or function affording safe and effective contraceptives for men and/or women. The NICHD also supports research to develop compounds for reproductive health related fields of research (e.g., infertility, gynecologic health, obstetrics and pediatrics, as well as pregnancy and perinatology). The Chemical Screening and Optimization Facility (CSOF) fulfills a unique role by identifying, optimizing, and conducting small scale production of molecular agents that achieve a contraceptive effect. The CSOF provides overall project management and the capabilities to support these objectives pursuant to development of new contraceptive methods: these include, but are not limited to, the generation of recombinant peptides and proteins, assay development, high throughput screening (HTS), x-ray crystallography, computational chemistry, medicinal chemistry, and pharmacology. Compounds identified and/or optimized by the CSOF will be prepared under non-Good Manufacturing Practices (non-GMP) for further preclinical evaluation. The CSOF plays a critical role in the drug development mission of the CRB. One approach to achieve this goal includes high throughput screening studies for the purpose of identifying hit compounds using High Throughput Screening (including computational approaches) for either contraceptive or reproductive health related targets. The research directed by this task order will utilize either in-house methods or appropriate subcontract facilities capable of high throughput screening, confirmatory assays (as needed) and/or in silico methods (as needed) or will be done in conjunction with a successful service request applicant who would assume responsibility for all biochemical and/or biological assays. Specifically, this Task Order is for the identification of small molecule(s) hits that engages a validated target either for inhibition or activation of a process for either contraception or a reproductive health related indication. It is expected that for a given service request up to 100 new chemical entities will be identified with biological properties consistent with conventional bioavailability design parameters (e.g. Lipinski’s Rule of 5) over a period of up to twelve months. At the conclusion of which, the identified hit compound/small molecule(s) will have a significant improvement over established positive controls for ligand affinity (e.g., IC50 < 1 uM, up to 100 fold improvement compared to positive control) as demonstrated using identified biochemical assays, cellular assays, appropriate counter screening efforts, safety considerations (PAINs compliant), and isoform selectivity (>25 fold, if applicable). The objective of this contract is for the Chemical Screening and Optimization...