AGI-5198 (IDH-C35) is the first highly potent and selective mutant IDH1 inhibitor that was shown to have anti-tumor efficacy and lower tumor 2‑HG (2-hydroxyglutarate) in vivo. It inhibits IDH1 R132H mutant and R132C mutant in vitro with IC50 ~0.07 µM and ~0.16 µM, respectively, but not wild-type IDH1 or any of the examined IDH2 isoforms (IC50 > 100 ¦ÌM). AGI-5198 has good cellular activities in TS603 glioma cell line, also inhibits 2-HG production in HT1080 and U87MG cells with IC50 ~0.48 µM and IC50 ~0.07 µM, respectively. In R132H-IDH1 glioma xenografts (TS603), AGI-5198 (450 mg/kg) caused 50-60% growth inhibition with no signs of toxicity during three weeks of daily treatment, but it did not affect the growth of IDH1 wild-type glioma xenografts (TS516). Under conditions of near complete R-2HG (R-2-hydroxyglutarate) inhibition, AGI-5198 induced demethylation of histone H3K9me3 and expression of genes associated with gliogenic differentiation. Blockade of mutant IDH1 impaired the growth of IDH1-mutant¡ªbut not IDH1-wild-type¡ªglioma cells without appreciable changes in genome-wide DNA methylation. AGI-5198 could serve as a very useful chemical probe to assess the biological consequences of IDH1 mutations and the potential of IDH1 inhibitor for treating IDH1 mutant tumors.

June 21, 2017

prudect name : AGI-5198 (IDH-C35) is the first highly potent and selective mutant IDH1 inhibitor that was shown to have anti-tumor efficacy and lower tumor 2‑HG (2-hydroxyglutarate) in vivo. It inhibits IDH1 R132H mutant and R132C mutant in vitro with IC50 ~0.07 µM and ~0.16 µM, respectively, but not wild-type IDH1 or any of the examined IDH2 isoforms (IC50 > 100 ¦ÌM). AGI-5198 has good cellular activities in TS603 glioma cell line, also inhibits 2-HG production in HT1080 and U87MG cells with IC50 ~0.48 µM and IC50 ~0.07 µM, respectively. In R132H-IDH1 glioma xenografts (TS603), AGI-5198 (450 mg/kg) caused 50-60% growth inhibition with no signs of toxicity during three weeks of daily treatment, but it did not affect the growth of IDH1 wild-type glioma xenografts (TS516). Under conditions of near complete R-2HG (R-2-hydroxyglutarate) inhibition, AGI-5198 induced demethylation of histone H3K9me3 and expression of genes associated with gliogenic differentiation. Blockade of mutant IDH1 impaired the growth of IDH1-mutant¡ªbut not IDH1-wild-type¡ªglioma cells without appreciable changes in genome-wide DNA methylation. AGI-5198 could serve as a very useful chemical probe to assess the biological consequences of IDH1 mutations and the potential of IDH1 inhibitor for treating IDH1 mutant tumors.
AGI-5198 (IDH-C35)

Synonyms: CAS NO: 1355326-35-0Molecular Formula: C₂₇H₃₁FN₄O₂Molecular Weight: 462.56Purity: 98% minSolubility: Storage: -20°C

24386-93-4 References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/18501959