Columbia University

Dana-Farber-Cancer Institute Inc.

Other

Johns Hopkins University

University of Pennsylvania

Amgen Inc.

Bryn Mawr College

Wayne A Hendrickson

Peter D Kwong

Joseph G Sodroski

Amos B Smith, Iii

Ernesto Freire

Richard Wyatt

Joel R Courter

Navid Madani

Judith M LaLonde

Amy M Princiotto

Matthew Le-Khac

Arne Schön

Takahiro Soeta

John R Mascola

David Michael Jones

Xuliang Jiang

Young Do Kwon

Xueling Wu

Keith E Langley

Danny Ng

Michael Farzan

Rashid Syed

Alexander W Sun

Toyoharu Kobayashi

Jongwoo Park

Yueh-Rong Ann Hsu

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

A modified polypeptide corresponding to an envelope glycoprotein of a primate lentivirus is described. The polypeptide has been modified from the wild-type structure so that it has cysteine amino acid residues introduced to create disulfide bonds, a cavity is filled with hydrophobic amino acids, a Proresidue is introduced at a defined turn structure of the protein, or the hydrophobicity is increased across the interface between different domains, while retaining the overall 3-dimensional structure of a discontinuous conserved epitope of the wild-type protein. Preferably, the polypeptide has more than one of those characteristics. Preferably, the primate lentivirus is HIV, and the protein is HIV-1 gp120.

Stabilized primate lentivirus envelope glycoproteins

A modified polypeptide corresponding to an envelope glycoprotein of a primate lentivirus is described. The polypeptide has been modified from the wild-type structure so that it has at least two of the glycosylation sites proximal to the CD4 binding site or chemokine receptor site altered so that the alteration prevents glycosylation at that site or where glycosylation sites distal to these sites have been derivatized with a molecular adjuvant, while retaining the overall 3-dimensional structure of a discontinuous conserved epitope of the wild-type protein. Preferably, the polypeptide has both changes. Preferably, the primate lentivirus is HIV, and the protein is HIV-1 gp 120.

Glycosylated modified primate lentivirus envelope polypeptides

This invention provides a computer based method for preparing a stem cell factor (SCF) analog comprising the steps of: (a) providing computer expression of the three dimensional structure of an SCF molecule using its crystal structure; (b) selecting from the computer expression of step (a) at least one site on the SCF molecule for alteration; (c) preparing a SCF molecule having an alteration at said at least one selected site; and (d) optionally, testing the SCF molecule for a desired characteristic. This invention also provides SCF analogs and SCF ligand analogs prepared according to the above-described method. Compositions comprising SCF analogs or SCF ligand analogs prepared according to the above-described method effective to treat a subject and a pharmaceutically acceptable carrier are provided, as are methods of treating a subject comprising administration of pharmaceutical compositions comprising the prepared SCF analogs and SCF ligand analogs prepared by the described methods. This invention also provides methods for designing compounds capable of binding to the SCF receptor site and compounds designed by the above-described methods.

Conjugated ligands for the stimulation of blood cell proliferation by effecting dimerization of the receptor for stem cell factor

This invention provides a non-naturally occurring targeted lipolytic compound comprising a lipolytic agent linked to a targeting agent. In an embodiment, the lipolytic agent is covalently attached to the targeting agent. In an embodiment, the lipolytic agent is a phospholipase and the targeting agent is a viral receptor. This invention further provides for therapeutic uses of the non-naturally occurring targeted lipolytic compound. In an embodiment, the non-naturally occurring targeted lipolytic compound neutralizes virions of the human immunodeficiency virus (HIV).

Non-naturally occurring targeted lipolytic compounds and related compositions and methods

Growing community of inventors

New York, NY, United States of America

Wayne A Hendrickson