Development of Novel Anti-Hiv Compounds

Background:
The HIV DRP Retroviral Replication Laboratory at the National Cancer Institute-Frederick is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize active anti-viral compounds. The technology is also available for exclusive and non-exclusive licensing.

Technology:
The subject invention identified two groups of active anti-viral compounds. The first group comprises aromatic, antimony-containing compounds, while the second group comprises aromatic tricarboxylic acids. Both groups were shown to inhibit viral particle assembly and inhibit the binding of nucleocapsid protein to nucleic acid. Recently, the first group, notably the lead molecule Stibavirin, also demonstrated the capability of blocking HIV-1 viral entry into CD4+ cells through binding to CD4 and inhibiting gp120-CD4 interaction, and they are well tolerated in vivo. Hence, these compounds are potent inhibitors of HIV and act via a novel mechanism, ideal for developing a new generation of anti- HIV medicine.

R&D Status:
In vivo preclinical data available, including data from efficacy, pharmacokinetics and preliminary toxicity studies.

Related Publication(s):
QE Yang et al. Discovery of small-molecule human immunodeficiency virus type 1 entry inhibitors that target the gp120-binding domain of CD4. J Virol. 2005 May;79(10):6122-6133. [PubMed abs]

Further R&D Needed: The path to the clinic for the lead antimony compound (Stibavirin) minimally requires; synthesis of adequate supply for toxicologic studies, conduct of those studies, and filing of an IND.

Value Proposition: The mechanism of anti-HIV action of Stibavirin is different from approved drugs. This new agent may therefore be useful in combination treatment of patients with AIDS, particularly those who have become resistant to other drugs.

IP Status:

• U.S. Patent Application filed March, 2005
• European Patent Application filed May, 2005

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

Reference:  #458 KH