Integrase strand transfer inhibitors (“INSTIs”) are currently in use as a component of prophylactic antiretroviral therapy for preventing HIV-1 infection from progressing to AIDS. Three INSTIs are approved by the FDA for inclusion in antiretroviral regiments: raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG). Clinicians have already identified several HIV-1 integrase mutations that confer resistance to RAL and EVG, and additional mutations that confer resistance to all three INSTIs has been identified in the laboratory.
Researchers at the National Cancer Institute discovered small-molecule compounds containing 1-hydroxy-2-oxo-1,8-naphthyridine moieties whose activity against HIV-1 integrase mutants confer resistance to currently approved INSTIs. These new compounds exhibit potent and selective activity against comprehensive and varied panels of INSTI-resistant mutants of HIV-1 integrase. Preliminary metabolic and pharmacokinetic studies have been completed by the NCI researchers.
The National Cancer Institute (NCI) seeks partners to in-license or co-develop this class of compounds for therapeutic use. Parties interested in licensing the technology should submit an Application for Licensing, and seek detailed information from the Licensing and Patenting Manager indicated below.
Co-development partners would apply under a Cooperative Research and Development (CRADA) to conduct pre-clinical studies. Under the CRADA, further in vitro and in vivo ADME, as well as IND-enabling studies, will be conducted by the partner on current and optimized lead compounds. Efficacy studies in non-human primates of select compounds are needed and will be part of the CRADA program. The CRADA scope will also include all aspects of toxicity studies, and synthesis scale up under GMP of optimized lead compounds to support submission of a successful IND application.
Licensing of background technology related to this CRADA opportunity is also available to potential collaborators.
- HIV therapeutic for drug-resistant mutants of HIV-1 integrase
- Currently, the only INSTI effective against drug resistant mutants of HIV-1 integrase
Terrence Burke (NCI), Stephen Hughes (NCI), Yves Pommier (NCI), Xue Zhao (NCI), Mathieu Metifiot (NCI), Stephen Smith (NCI), Barry Johnson (NCI), Christophe Marchand (NCI)
Zhao X, et al. HIV-1 Integrase Strand Transfer Inhibitors with Reduced Susceptibility to Drug Resistant Mutant Integrases. [PMID: 26808478]
Smith, S.J. HIV-1 Integrase Inhibitors That Are Active against Drug-Resistant Integrase Mutants 
Smith, S.J. Integrase Strand Transfer Inhibitors Are Effective Anti-HIV Drugs 
- U.S. Patent Issued: U.S. Patent Number 10,208,035, Filed 08 May 2017, Issued 19 Feb 2019
- U.S. Patent Issued: U.S. Patent Number 9,676,771, Filed 16 May 2013, Issued 13 Jun 2016