University of Pennsylvania

Dana-farber-cancer Institute Inc.

Bryn Mawr College

Other

Johns Hopkins University

Columbia University

Navid Madani

Amos B Smith, Iii

Joseph G Sodroski

Amy M Princiotto

Judith M LaLonde

Ernesto Freire

Joel R Courter

Wayne A Hendrickson

Takahiro Soeta

Matthew Le-Khac

Peter D Kwong

John R Mascola

David Michael Jones

Young Do Kwon

Xueling Wu

Danny Ng

Bruno Melillo

Alexander W Sun

Arne Schön

Toyoharu Kobayashi

Jongwoo Park

The disclosure provides compositions and methods for sensitizing primary HIV-1, including transmitted/founder viruses, to neutralization by monoclonal antibodies, e.g., those directed against CD4-induced (CD4i) epitopes and the V3 region. In certain embodiments, the disclosure relates to the use of small molecules as microbicides to inhibit HIV-1 infection directly and to sensitize primary HIV-1 to neutralization by readily elicited antibodies.

Inhibitors of HIV-1 entry and methods of use thereof

The invention provides for compounds of formula I: wherein Z is absent or (CRR)W; each RA and RB is independently (i) H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, haloalkyl, each of which may be optionally substituted; (ii) OH, ORc, NH2, NHR, NRR, SH, S(O)R; or (iii) Rand Rtogether form C(O); W is absent, C(O), C(O)O, C(O)NRR, O, S(O), or NRR; Y is an optionally substituted heterocyclic, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted aryl, or NRR; wherein Rand Rare each independently H, alkyl or aryl; Xis selected from the group consisting of halogen, methyl, and hydroxyl; X2 is a halogen; each Ris independently alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl, each of which may be optionally substituted; m is O, 1, or 2; and n is 1, 2, 3, 4, 5, or 6; and pharmaceutically acceptable salts thereof. 

Small molecule CD4 mimetics and uses thereof

Described herein are small-molecule mimics of CD4, which both enter the Phe43 cavity and target Asp368 of gp120, the HIV-1 envelope protein. Also described herein are methods of using these compounds to inhibit the transmission or progression of HIV infection. These compounds exhibit antiviral potency greater than that of a known antiviral, NBD-556, with 100% breadth against clade B and C viruses. Importantly, the compounds do not activate HIV infection of CD4-negative, CCR5-positive cells, in contrast to NBD-556.

CD4-mimetic inhibitors of HIV-1 entry and methods of use thereof

Growing community of inventors

Newton, MA, United States of America

Navid Madani