Novel HIV Entry Inhibitors with very low Nanomolar Potency

PAGE TITLE

Overview

 

PAGE SUMMARY

One million Americans are living with HIV/AIDS and 50,000 Americans per year are newly infected with the disease.  The evolution of multi-drug resistant HIV makes the virus difficult to target without combination therapy, and there is a need for new inhibitors of HIV-1 replication.  Moreover, the toxicities associated with available HAART regimens remains a considerable problem.  Current targets for most standard HIV therapies include the viral enzymes reverse transcriptase and protease.  Recently, a new class of viral integrase inhibitors has become available for use in the clinic.  Emerging drug targets for HIV therapies include inhibitors that directly or indirectly block the function of the HIV-1 Env complex, responsible for entry of the virion into the host cell (so-called entry inhibitors).  Using a combination of computer-aided drug discovery protocols and in vitro testing, the Cocklin lab has identified new small molecules that inhibit HIV entry into cells with low nanomolar potency.

 

APPLICATIONS

TITLE: Applications

 

Enhancement of viral targets for HIV combination therapies

 

ADVANTAGES

TITLE:Advantages

 

Very low nanomolar IC50 values

Hits emerging HIV drug target, Env

Compounds have improved drug-like properties and better predicted ADME than other entry inhibitors as judged by state-of-the-art predictive ADME software

 

 IP STATUS

Intellectual Property and Development Status

Issued United States patent 9,920,073

https://patents.google.com/patent/US9920073B2/en?oq=9%2c920%2c073

 

 

PUBLICATIONS

References

 

Tuyishime et al. Discovery and optimization of novel small molecule HIV-1 entry inhibitors using field-based virtual screening and bioisosteric replacement. Bioorg. Med. Chem. Letters, 2014.

https://www.ncbi.nlm.nih.gov/pubmed/25454268

 

Meuser M.E. et al.  Kinetic Characterization of Novel HIV-1 Entry Inhibitors: Discovery of a Relationship between Off-Rate and Potency.  Molecules, 2018, 23(8), 1940.

http://www.mdpi.com/1420-3049/23/8/1940

 

Contact Information     

 

Robert McGrath

Sr AVP for IP & Agreements

RBM@Drexel.edu

 

 

Patent Information: