Mutant IDH1 inhibitor

Mutant IDH1 inhibitor is a potent mutant IDH1 R132H inhibitor with IC50 of < 72 nM.

Signaling Pathways >> Metabolic Enzyme/Protease >> Isocitrate Dehydrogenase (IDH)

Research Areas >> Cancer

IC50: < 72 nM (mutant IDH1 R132H)

Mutant IDH1 inhibitor is a potent IDH1 R132H inhibitor, and used for the treatment of diseases or disorders associated with such mutant IDH proteins including, but not limited to, cell-proliferation disorders, such as cancer[1].

Day 1: cells are seeded in 384-well plates in triplicates for both the cell proliferation and 2HG assay, and incubated at 37°C, 95% Rh, 5% CO2 overnight. Day 2: compounds are serially diluted 1 :3 (10 point dilution from 10 mM solutions in DMSO) and delivered to the cell assay plates via acoustic dispenser, with final concentration ranging from 30 μM to 1.5 nM. The plates are returned to the incubator after treatment and incubated for 48 hours. Day 4 Proliferation assay: CTG is added to the assay plates and luminescence signal is read on the plate reader. Day 4 2HG assay : Extraction sample preparation consisted of aspirating all media from the assay plates, adding 70 μL of 90% methanol in water, dry ice incubation for 15 minutes, centrifuging at 2000 rpm for 30 min to ensure all particulates have settled, and transferring 30 μL of the supernatant into LC-MS ready plates. LC-MS analysis follows.

[1]. 3-Pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant IDH and their preparation. Patent WO 2013046136 A1 20130404

AG-120 | Enasidenib | AGI-5198 | Vorasidenib (AG-881) | AGI-6780 | GSK864 | IDH-305 | BAY-1436032 | Mutant IDH1-IN-1 | Mutant IDH1-IN-2 | Olutasidenib