University of Pittsburgh

Thomas E Smithgall

Billy W Day

Lori Ann Emert-Sedlak

Prema Chandrasekhar Iyer

Toshiaki Kodama

Weixiang Dai

Jielu Zhao

Ronald P Trible

A method of treating HIV in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of a compound having a general Formula 1, or a pharmaceutically acceptable salt or ester thereof: wherein Ris selected from H, optionally-substituted aryl, optionally-substituted heteroaryl, or optionally-substituted aliphatic; each Ris independently selected from H, halogen, cyano, thioether, oxo, optionally-substituted amino, optionally-substituted heteroaryl, optionally-substituted aryl, or optionally-substituted aliphatic; a is 3 to 7; and the ring designates a heterocyclic or heteroaryl structure.

Small molecules targeting HIV-1 nef

Small molecules targeting HIV-1 Nef

Disclosed herein are embodiments of a compound capable of treating HIV. In particular disclosed embodiments, the compound is capable of inhibiting Nef, such as by acting as antagonists of HIV Nef function. Also disclosed are embodiments of a method of making the compound, embodiments of a method of using the compound, and embodiments of a method of identifying HIV Nef antagonists. The disclosed compound may be used alone or in combination with other pharmacologically active agents in order to promote reducing drug resistance and/or cumulative toxicity.

Compounds for treating HIV and methods for using the compounds

Drug candidates for inhibition of HIV-I replication can target Src family kinases (SFK), such as Hck, that interact with Nef protein of the virus. Compounds characterized by such inhibitory activity were identified via an assay for kinase activity of an SFK in a Nef:SFK complex. Illustrative of inhibitors identified using the kinase assay are various 2,3-diaminoquinaxolines and furo[2,3-d]pyrimidines. The inventive inhibitors were found to arrest HIV-I viral replication in vitro.

Targeting an HIV-1 nef-host cell kinase complex

Growing community of inventors

Wexford, PA, United States of America

Thomas E Smithgall