Mutant IDH1-IN-1

Mutant IDH1-IN-1 (Agios 135) is a selective mutant IDH1 inhibitor with activity against both IDH1^R132H and IDH1^R132C. Mutant IDH1-IN-1 reduces the level of 2-hydroxyglutarate (2-HG), stabilizes mutant IDH1 protein, and restores blocked monocyte differentiation. Mutant IDH1-IN-1 can be used in tumor-related research^[1]. IC50 & Target:IC50: 4 nM (IDH1 R132C/R132C), 42 nM (IDH1 R132H/R132H), 80 nM (IDH1 R132H/WT), 143 nM (IDH1 wild type)^[1] In Vitro:Mutant IDH1-IN-1 (30-50 min) potently inhibits purified recombinant IDH1^R132H (with an IC₅₀ of 0.38 µM) and IDH1^R132C (with an IC₅₀ of 0.09 µM), exhibits only weak activity against wild-type IDH1, and shows no activity against wild-type IDH2^[1].
Mutant IDH1-IN-1 (48 h) reduces 2-HG production in HT1080 (IDH1^R132C), SNU1079 (IDH1^R132C), RBE (IDH1^R132S), JJ012 (IDH1^R132G), U87 (IDH1^R132H) and THP-1 (IDH1^R132H) cells without significant cytotoxicity^[1].
Mutant IDH1-IN-1 (0.5 µM; 4 days) rescues doxycycline (HY-N0565)-induced monocytic differentiation of THP-1 (IDH1^R132H) acute myeloid leukemia (AML) cells^[1].
Mutant IDH1-IN-1 (4 days) reduces 2-HG production in 3D tumor spheres of HT1080 (R132C), JJ012 (R132G), and U87 (R132H)^[1].
Mutant IDH1-IN-1 (compound 2) (30 min) potently inhibits the de novo reductive activity of the homodimeric IDH1^R132H, with an IC₅₀ of 0.042 μM^[2].
Mutant IDH1-IN-1 (30 min) potently inhibits the de novo reductive activity of the homodimeric IDH1^R132C, with an IC₅₀ of 0.004 μM^[2].
Mutant IDH1-IN-1 (30 min) inhibits the de novo reductive activity of the heterodimer IDH1^R132H/WT, with an IC₅₀ value of 0.080 μM^[2].
Mutant IDH1-IN-1 (30 min) inhibits the oxidative activity of the heterodimeric R132H/WT IDH1, with an IC₅₀ of 0.143 μM^[2].
Mutant IDH1-IN-1 (30 min) inhibits the oxidative activity of the homodimeric WT/WT IDH1, with an IC₅₀ value of 1.998 μM^[2].