Agios Pharmaceuticals, Inc.

Servier Pharmaceuticals LLC

Les Laboratoires Servier

Zenon D Konteatis

Jeremy Mark Travins

Janeta Popovici-Muller

Robert Zahler

Ding Zhou

Zhenwei Cai

Zhihua Sui

Zhixiong Ye

Samuel K Reznik

Mingzong Li

Jeremy M Travins

Brian Christopher Shook

Guangning Ma

Matthew Medeiros

Shubao Zhou

Peng Liu

Sandra King

Heather Jane Finlay

Lucrezia De Pascalis

Provided are compounds useful for treating cancer and methods of treating cancer comprising administering to a subject in need thereof a compound described herein.

Therapeutically active compounds and their methods of use

The present disclosure provides for compounds according to Formula I and their pharmaceutically acceptable salts, tautomers, and/or isotopologues as described in the disclosure. The compounds are inhibitors of methionine adenosyltransferase isoform 2A (MAT2A). Also provided are pharmaceutical compositions and methods of using the compounds for treating cancers, including some cancers in which the gene encoding methylthioadenosine phosphorylase (MTAP) is deleted.

Aza-heterobicyclic inhibitors of MAT2A and methods of use for treating cancer

The present disclosure provides MAT2A inhibitor compounds that are useful as therapeutic agents for treating malignancies, and wherein the compounds conform to general formula (IA): wherein R, R, R, R, and Rare defined herein.

Inhibitors of cellular metabolic processes

The disclosure relates to compounds of Formula I or a pharmaceutically acceptable salt thereof, wherein, m, R-R, R, and L are defined herein. These compounds are useful in methods for stabilizing a mutant PAH protein or reducing blood phenylalanine concentration in a subject suffering from phenylketonuria. In some embodiments, the mutant PAH protein contains at least one R408W, R261Q, R243Q, Y414C, L48S, A403V, I65T, R241C, L348V, R408Q, or V388M mutation. In other embodiments, the mutant PAH protein contains at least one R408W, Y414C, I65T, F39L, R408Q, L348V, R261Q, A300S, or L48S mutation.

Compounds and methods useful for stabilizing phenylalanine hydroxylase mutations

The present disclosure provides for compounds according to Formula I or Formula II and their pharmaceutically acceptable salts, stereoisomers, and/or tautomers thereof. Also provided are pharmaceutical compositions and the compounds of formulae I and II for use in methods of treating cancers, via inhibition of MAT2A, including some cancers in which the gene encoding methylthioadenosine phosphorylase (MTAP) is deleted and/or not fully functioning. 

Heterobicyclic inhibitors of MAT2A and methods of use for treating cancer

Provided are compounds of formula (I), wherein: ring A and ring B are each independently an optionally substituted 5-6 membered monocyclic aryl or heteroaryl; one of X, Y and W is CH and the two others are N; and Z is H or &#x2014;C(R1)(R2)(R3). The compounds are inhibitors of isocitrate dehydronenase 2 (IDH2) mutants useful for treating cancer. 

2,4- or 4,6-diaminopyrimidine compounds as IDH2 mutants inhibitors for the treatment of cancer

Growing community of inventors

Chatham, NJ, United States of America

Zenon D Konteatis