Molsoft LLC

University of California

New York University

Eil Therapeutics, Inc.

The General Hospital Corporation

University of Massachusetts

Ruben Abagyan

Maxim Totrov

Alexandre Vasilievich Ivachtchenko

Alexei Pushechnikov

Vladislav Zenonovich Parchinsky

Volodymyr Kysil

Polo Chun-Hung Lam

Nikolay Savchuk

Andrew Orry

Stephen R Wilson

Susan Zolla-Pazner

Timothy J Cardozo

Abraham Pinter

Shan Lu

Herbert H Samuels

Aleksey G Kazantsev

Bruce M Raaka

Zhiguo Zhou

Miroslaw K Gorny

Xiang-peng Kong

Leslie Thompson

Matthieu Schapira

Li Fan

Eugene Raush

Malcolm Casale

Levon Budagyan

Andrew J W Orry

Ittipat Meewan

Hepatitis C virus (HCV) is a human pathogen with high morbidity. The HCV NS3/4A protease is essential for viral replication and is one of top three drug targets. A number of drugs have been developed but drug resistant mutant strains emerged. Here we screened and synthesized of novel class of small molecules of Formula I or Formula IA based on tryptophan derivative scaffold as HCV NS3/4A protease inhibitors that is active against both wild type and mutant form of the protease. Only the docking hits with a binding pose that is not affected by the most frequent mutations in the active site were selected for experimental validation. The antiviral activities were evaluated by replicon and enzymatic assays. Twenty-two compounds in this series were found to inhibit HCV with ECvalues ranging between 0.64 to 63 μM with compound 22 being the most active of this series. In protease assays, 22 had a comparable inhibition profile for the common mutant HCV GT1b D168A and the wild type enzyme. However, in the same assay, potency of the approved drug, Simeprevir, decreased 5.7-fold for the mutant enzyme relative to the wild-type. The top three inhibitors were also tested against four human serine proteases and were shown to be specific to the viral protease. The fluorescent based cell viability assay demonstrated a sufficient therapeutic range for the top three candidates.

HCV protease inhibitors

The present invention is generally directed to inhibitors of BCL-2 proteins useful in the treatment of diseases and disorders modulated by said enzyme and having the Formula (I):

Compounds having ((3-nitrophenyl)sulfonyl)acetamide as BCL-2 inhibitors

Compounds having tetrahydroindolizine-1-carboxamide as BCL-2 inhibitors

This disclosure relates to compounds that act as activators of the NRF2/KEAP1/ARE pathway. Specifically, the compounds provided herein can act as high affinity reversible bindings for the NRF2 inhibitor, KEAP1. In some cases, NRF2/KEAP1/ARE pathway activation compounds are capable of repressing expression of inflammatory markers and/or reducing levels of TNFa to provide neuroprotective anti-inflammatory effects in the CNS. Such compounds are useful in the treatment of a variety of diseases including Huntington's disease, Parkinson's disease, Alzheimer's disease, inflammation, and cancer.

Small molecule activators of NRF2 pathway

Insertion of HIV-1 V3 loop peptides from the viral glycoprotein gp120 into selected, immunogenic scaffold proteins results in a recombinant polypeptide that is a potent V3 immunogen. V3 immunogens include natural and consensus V3 sequences and cyclic and reverse peptides. Preferred scaffold proteins are Cholera Toxin subunit B and homologues thereof including closely relatedenterotoxins. Such immunogenic polypeptides induce broadly reactive anti-gp120 antibodies specific for V3 epitopes that can neutralize heterologous HIV-1 subtypes and strains. These polypeptide, methods for preparing them, and methods for inducing anti-gp120 (V3-specific) antibody) responses using them are disclosed.

Immunogen comprising the HIV GP120 V3 loop in a conformation that induces broadly neutralizing antibodies

A method of identification of compounds that modulate thyroid hormone activity, and the use of such compounds and compositions thereof for such purposes are disclosed. The compounds may be selected from the group consisting of: The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of conditions that are causally related to aberrant thyroid hormone activity, such as hyperthyroidism and thyrotoxicosis.

Hydrazide compounds as thyroid hormone receptor modulators and uses thereof

A structured document file which includes graphical and non graphical information. The graphical information includes the vector and coordinate description of a representation of at least one three dimensional object and at least one of the following group of view attributes or features: rotation, translation, view angle, lighting, colors, specific graphical representations, labels and parameters. The vector and coordinate description are stored with or independently from the one or more view attributes or features and the vector and coordinate description and the one or more view attributes are stored in a single file which can be accessed and viewed by a structured document viewer. Related authoring tools and viewers are also disclosed.

Structured documents and systems, methods and computer programs for creating, producing and displaying three dimensional objects and other related information in those structured documents

Growing community of inventors

La Jolla, CA, United States of America

Ruben Abagyan