A -- Chemical Optimization and Preclinical Development of Molecular-Targeted Anticancer, Antiviral and Antimicrobial Drug Leads

The National Cancer Institute (NCI)-Developmental Therapeutics Program (DTP) - Screening Technologies Branch (STB) seeks Cooperative Research and Development Agreement (CRADA) collaborator(s) to participate in the optimization of small molecule, molecular-targeted anticancer, antiviralb-d and/or antimicrobial screening leads for potency and pharmaceutical properties consistent with clinical developmenta. The leads have been identified by the NCI-STB using high-throughput screening and preliminary structure/activity study of 140,000 samples from an NCI repository addressing a number of molecular targets of potential therapeutic significance. Potential Areas if Application: Antitumor, antiviralb-d (HIV) and antimicrobial agents. Specifically, opportunities are available to optimize antitumor leads for inhibition of Hypoxia Inducible Factor-1 (HIF-1) alpha signaling and for inducers of the CCAAT/Enhancer Binding Protein (CEBP- ) signaling pathway and for antiviral inhibitors of HIV-1 virus assemblyc,d. Main Advantages of the Technology: Lead compounds possess distinct mechanisms of antiviral and antitumor activities. Current State of Development: In vitro evaluation and preliminary structure/activity studies on-going at NCI for existing leads. Further R&D Requireda: Initially, a medicinal chemistry partner is sought to identify and resolve potential structural problems / features thus optimizing lead compound(s) for activity, potency, formulation, stability, metabolism, toxicity, absorption/distribution etc. Secondary or in vivo biological testing would be carried out by the NCI-Screening Technologies Branch. In a second stage, in vivo active compounds will be subjected to additional analysis and analogs will be synthesized to further optimize structure/activity properties. Patent Status and Pertinent References: a) Federal Register, November 8th, 2002, Volume 67, No. 217, pp. 68143-68144. "National Cancer Institute: Chemical Optimization of Molecular- Targeted Anticancer, Antiviral and Antimicrobial Drug Leads". b) U.S. Patent Application filed on February 5, 2001, "Method of Inhibiting a Viral Replication Targeting the Nucleocapsid Protein." c) U.S. Patent Application filed on October 8, 2002, "Identification of anti-HIV compounds inhibiting virus assembly and binding of nucleocapsid protein to nucleic acid". d) Stephen et al., Biochem. Biophys. Res. Comm. 296, 1228 (2002). Contact Information: Bjarne Gabrielsen, Ph.D., Technology Development & Commercialization Branch, NCI-Frederick, Fairview Center, Suite 502, 1003 - W. 7th Street, Frederick, MD 21701-8512. Phone: (301) 846-5465; email: [email protected]. Last Updated 8/04/2004