A -- National Cancer Institute is seeking CRADA partners to pursue chemical optimization of molecular-targeted anticancer, antiviral, and antimicrobial drug leads

The Developmental Therapeutics Program (DTP), Division of Cancer Treatment and Diagnosis, National Cancer Institute is seeking CRADA partners to pursue chemical optimization of molecular-targeted anticancer, antiviral, and antimicrobial drug leads. The Screening Technologies Branch (STB) of DTP has completed high-throughput screening campaigns of more than 140,000 samples from the NCI repository addressing a number of molecular targets of potential therapeutic significance. Lead compounds with potent and selective activity have been identified in a number of target areas. Preliminary structure-activity studies have been performed with available chemical analogs. Additional work is needed to optimize the screening leads for potency and pharmaceutical properties consistent with clinical development. This is envisioned primarily as a two-stage process. In the first stage, the structures of screening leads will be reviewed by an expert medicinal chemist (CRADA partner) to identify potential problems related to formulation, chemical stability, metabolism, toxicity, etc. Based on this analysis, lead compounds may be subjected to secondary and in vivo testing directly, or a series of derivatives/analogs may designed to obviate problems. Derivative compounds will be tested in the primary screening models to demonstrate retention of targeting activity and selected active compounds will then be tested in secondary and in vivo models. In the second stage of optimization, in vivo active compounds will be subjected to additional analysis and additional derivatives/analogs will be synthesized to further optimize activity. Additional iterations may be performed to define clinical development candidates. All biological testing will be performed by DTP. Opportunities are currently available to optimize leads for inhibition of HIF-1 (Hypoxia Inducible Factor-1) alpha signaling, for inducers of CEBP alpha signaling, and for inhibition of HIV-1 virus assembly. Additional opportunities are anticipated during the next six months.Contact Dr. Bjarne Gabrielsen for more information at +1 (555) 000-0000