Anti-HIV Nucleoside Analogs

Background:
The National Cancer Institute's HIV Drug Resistance Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize drugs with activity against HIV-1.

Technology:
This invention describes a new use for C4'-methyl-2-dexoyadenosine, a nucleoside analog that has significant activity against HIV-1 and most strains of HIV previously shown to be resistant to other reverse transcriptase nucleoside inhibitor treatments. In vitro experimental results show substantial anti-HIV activity (blocked infectivity) with no observable cytotoxicity in cell culture. Mechanistic studies have revealed that this compound blocks DNA synthesis by reverse transcriptase.

Further R&D Needed:

• Obtain a crystal structure of the nucleoside triphosphate in complex with HIV-1 reverse transcriptase and nucleic acid to determine the nature of the enzyme-inhibitor complex.
• Selection of drug-resistant mutations in vitro using replication-competent virus in cell culture.
• Determine the in vivo safety and toxicity using animal models.
• Determine the pharmacokinetics and pharmacodynamics of the nucleoside analog.
• Determine optimal formulation(s) of the compound in preparation for clinical trials.

R&D Status:
In vitro data has been collected and can be provided upon request.

IP Status:
U.S. Provisional Application No. 61/002,711 filed 09 Nov 2007

Value Proposition:

• Nucleoside analog against HIV-1 reverse transcriptase with no observable cytotoxicity in cell culture
• Potential new treatment for HIV-1 infections including infections by strains of HIV-1 that are resistant to nucleoside reverse transcriptase inhibitors

Contact Information:
John D. Hewes, Ph.D.
NCI Technology Transfer Center
Phone: 301-435-3121
E-mail: Hewesj@mail.nih.gov

Reference:  #663 MC

Posted 07/16/2008