The United States of America, as Represented by the Secretary, Department of Health and Human Services

University of Pennsylvania

Dana-Farber-Cancer Institute Inc.

Vanderbilt University

The Uab Research Foundation (the University of Alabama at Birmingham)

Whitehead Institute for Biomedical Research

Ganesha Rai Bantukallu

Anton Simeonov

David Joseph Maloney

Ajit Jadhav

Kyle Ryan Brimacombe

Li Liu

Alex Gregory Waterson

David Sabatini

William J Moore

Gary Allen Sulikowski

Kwangho Kim

Min Shen

Matthew E Hall

Matthew Brian Boxer

Xin Hu

Leonard M Neckers

Plamen P Christov

David J Maloney

Daniel Jason Urban

Shyh Ming Yang

Victor M Darley-Usmar

Somnath Jana

Jason Matthew Rohde

Chi V Dang

Bryan T Mott

Jennifer L Kouznetsova

Thomas Kristie

Yu Liang

Michael Pacold

Jodi Vogel

Matthew Hall

Brian T Mott

Plamen Christov

The present invention provides compounds of Formula (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, pro-drugs, and compositions thereof. Also provided are methods and kits involving the compounds of Formula (I), (II) or (III) for treating diseases associated with the over-expression of phosphoglycerate dehydrogenase (PHGDH) in a subject, such as proliferative diseases (e.g., cancers (e.g., breast cancer, ER negative breast cancer, melanoma, cervical cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases). Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the activity of PHGDH or inhibit the serine biosynthetic pathway, or both.

Inhibitors of phosphoglycerate dehydrogenase (PHGDH) and uses thereof

The disclosure provides a compound of the formula (II) and pharmaceutically acceptable salts thereof. The variables, e.g. n, R, R, R, X, Y, and Z are defined herein. These compounds act as lactate dehydrogenase inhibitors and are useful for treating cancer and fibrosis. The compounds may be particularly useful for treating forms of cancer in which a metabolic switch from oxidative phosphorylation to glycolysis has occurred. The disclosure also provides pharmaceutical compositions containing a compound of this formula and method for treating patients having cancer, fibrosis, or other conditions in which a metabolic switch from oxidative phosphorylation to glycolysis has occurred. 

1 H-pyrazol-1-yl-thiazoles as inhibitors of lactate dehydrogenase and methods of use thereof

Disclosed are compounds and pharmaceutical compositions containing compounds that inhibit JMJD2 proteins, including those of the formula (I): wherein R, R, R, R, and Rare as defined herein or pharmaceutically acceptable salts thereof. Also disclosed is a method of preventing or treating a viral infection of a host, comprising administering to the host an effective amount of an inhibitor of the JMJD2 family of histone demethylases, for example, a compound of the formula (I). The viral infection may be a primary infection, reactivation of a virus after latency in a host, or may be in a mammal that has undergone, is undergoing, or will undergo immunosuppressive therapy.

Method of preventing or treating viral infection

Growing community of inventors

Arlington, VA, United States of America

Ganesha Rai Bantukallu