Janeta Popovici-Muller

TL;DR: The recent discovery of mutations in metabolic enzymes has rekindled interest in harnessing the altered metabolism of cancer cells for cancer therapy, and isocitrate dehydrogenase 1 (IDH1), which is mutated in multiple human cancers, is examined.

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: 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: 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.