Discovery of the First Potent Inhibitors of Mutant IDH1 That Lower Tumor 2-HG in Vivo
J Popovici-Muller, JO Saunders… - ACS medicinal …, 2012 - ACS Publications
ACS medicinal chemistry letters, 2012•ACS Publications
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.
Compound 35 shows good potency in the U87 R132H cell based assay and∼ 90% tumor 2-
HG inhibition in the corresponding mouse xenograft model following BID dosing. The
magnitude and duration of tumor 2-HG inhibition correlates with free plasma concentration.
first potent molecules that show robust tumor 2-HG inhibition in a xenograft model.
Compound 35 shows good potency in the U87 R132H cell based assay and∼ 90% tumor 2-
HG inhibition in the corresponding mouse xenograft model following BID dosing. The
magnitude and duration of tumor 2-HG inhibition correlates with free plasma concentration.
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. Compound 35 shows good potency in the U87 R132H cell based assay and ∼90% tumor 2-HG inhibition in the corresponding mouse xenograft model following BID dosing. The magnitude and duration of tumor 2-HG inhibition correlates with free plasma concentration.
ACS Publications