IDH1 Inhibitor 1

• CAT Number: I019618
• CAS Number: 2234285-81-3
• Molecular Formula: C20H18F4N6O2
• Molecular Weight: 450.39
• Purity: ≥95%
• Synonyms: (4R)-4-(fluoromethyl)-3-[2-[[(1S)-1-[1-[4-(trifluoromethyl)phenyl]imidazol-4-yl]ethyl]amino]pyrimidin-4-yl]-1,3-oxazolidin-2-one
• InChI: InChI=1S/C20H18F4N6O2/c1-12(16-9-29(11-26-16)14-4-2-13(3-5-14)20(22,23)24)27-18-25-7-6-17(28-18)30-15(8-21)10-32-19(30)31/h2-7,9,11-12,15H,8,10H2,1H3,(H,25,27,28)/t12-,15-/m0/s1
• InChIKey: ULTZLMKTFYRMFK-WFASDCNBSA-N
• SMILES: CC(C1=CN(C=N1)C2=CC=C(C=C2)C(F)(F)F)NC3=NC=CC(=N3)N4C(COC4=O)CF

IDH1 Inhibitor 1 is a potent, orally bioavailable, brain-penetrant and selective mutant IDH1 inhibitor with IC50s of 0.021 μM, 0.045 μM, and 2.52 μM for IDH1R132H, IDH1R132C, and IDH1WT, respectively[1]. Anticancer activity[1].
IDH1 Inhibitor 1 (Compound 19) inhibits cellular HCT116-IDH1R132H/+ with an IC50 of 0.039 μM[1].
IDH1 Inhibitor 1 (Compound 19) inhibits 2-hydroxyglutarate (2-HG) production in a preclinical xenograft tumor model. IDH1 Inhibitor 1 is also profiled in a patient-derived IDH1 mutant HCT116-IDH1R132H/+ mechanistic xenograft tumor model in mice to evaluate in vivo inhibition of 2-HG production. IDH1 Inhibitor 1, dosed orally at 150 mg/kg, inhibits new 2-HG production[1].

Reference

[1]. Zhao Q, et al. Optimization of 3-Pyrimidin-4-yl-oxazolidin-2-ones as Orally Bioavailable and Brain Penetrant Mutant IDH1 Inhibitors. ACS Med Chem Lett. 2018 Jun 11;9(7):746-751.
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