Jeremy Travins

TL;DR: Evidence is provided that inhibitors targeting mutant IDH2/R140Q could have potential applications as a differentiation therapy for cancer, and a small molecule, AGI-6780, that potently and selectively inhibits the tumor-associated mutant IDh2/ R140Q is developed.

TL;DR: Findings define an enantiomer-specific mechanism by which the (R)-2HG that accumulates in IDH mutant brain tumours promotes transformation and provide a justification for exploring EGLN inhibition as a potential treatment strategy.

TL;DR: It is shown that mutant IDH blocks liver progenitor cells from undergoing hepatocyte differentiation through the production of 2HG and suppression of HNF-4α, a master regulator of hepatocyte identity and quiescence, and presents a novel genetically engineered mouse model of IDH-driven malignancy.

TL;DR: It is shown that the targeted inhibitor AG-221 suppresses the mutant IDH2 enzyme in multiple preclinical models and induces differentiation of malignant blasts, supporting its clinical development.

TL;DR: AG-120 (ivosidenib), an inhibitor of the IDH1 mutant enzyme that exhibits profound 2-HG lowering in tumor models and the ability to effect differentiation of primary patient AML samples ex vivo is reported.