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NCATS-SM5637 (NSC 791985) is a potent, selective mutant IDH1 inhibitor with IC50 of 81/72 nM for IDH1 mutant R132H/R132C, respctively.NCATS-SM5637 showed higher tumoral concentrations that corresponded to lower 2-HG concentrations in engineered mIDH1-U87-xenograft mouse model, compared with the approved drug AG-120 (ivosidenib).
AGI-12026 is brain-penetrant dual inhibitor of mutant IDH1 and 2. AGI-12026 shows partial inhibition of the IDH1-R132H homodimer as allosteric modulators. AGI-12026 has the potential for research of glioma.