Jeffrey O. Saunders

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: Kinetic analyses suggest that these inhibitors bind after the release of nicotinamide from the enzyme and prevent therelease of deacetylated peptide and O-acetyl-ADP-ribose, the products of enzyme-catalyzed de acetylation.

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.

TL;DR: Optimization of a series of R132H IDH1 inhibitors from a high throughput screen led to the first potent molecules that show robust tumor 2-HG inhibition in a xenograft model.