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