AGI-5198

• CAS: 1355326-35-0
• Catalog Number: ACM1355326350
• Category: Inhibitors
• Molecular Weight: 462.56
• Molecular Formula: C27H31FN4O2
• Description: AGI-5198, also know as IDH-C35, is the a very potent and selective mutant IDH1 inhibitor that was shown to potential anticancer activity. AGI-5198 shows good potency in the U87 R132H cell based assay and ~90% tumor 2-HG inhibition in the corresponding mouse xenograft model following BID dosing. AGI-5198 inhibits IDH1 R132H mutant and R132C mutant in vitro with IC50 ~0.07 μM and ~0.16 μM, respectively.
• Synonyms: AGI5198; AGI-5198; AGI 5198; IDHC35; IDH-C35; IDH C35
• IUPAC Name: N-cyclohexyl-2-(N-(3-fluorophenyl)-2-(2-methyl-1H-imidazol-1-yl)acetamido)-2-(o-tolyl)acetamide
• Canonical SMILES: O=C(NC1CCCCC1)C(N(C2=CC=CC(F)=C2)C(CN3C=CN=C3C)=O)C4=CC=CC=C4C
• InChI: InChI=1S/C27H31FN4O2/c1-19-9-6-7-14-24(19)26(27(34)30-22-11-4-3-5-12-22)32(23-13-8-10-21(28)17-23)25(33)18-31-16-15-29-20(31)2/h6-10,13-17,22,26H,3-5,11-12,18H2,1-2H3,(H,30,34)
• InChI Key: FNYGWXSATBUBER-UHFFFAOYSA-N
• Solubility: Soluble in DMSO, not in water
• Appearance: White to off-white solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: AGI-5198 (IDH-C35) is a potent and selective mutant IDH1R132H inhibitor with an IC50 of 0.07 μM.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 70.11; H, 6.76; F, 4.11; N, 12.11; O, 6.92
• Exact Mass: 462.2431
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: The activity of AGI-5198 in TS603 glioma cells with an endogenous heterozygous R132H-IDH1 mutation, the most common IDH mutation in glioma, was explored. TS603 cells were derived from a patient with anaplastic oligodendroglioma (WHO grade III) and harbor another pathognomomic lesion for this glioma subtype, namely co-deletion of the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q) (19) (Fig. 1C). Measurements of R-2HG concentrations in pellets of TS603 glioma cells demonstrated dose-dependent inhibition of the mutant IDH1 enzyme by AGI-5198 (Fig. 1D). When added to TS603 glioma cells growing in soft agar, AGI-5198 inhibited colony formation by 40 to 60% (Fig. 1E). AGI-5198 did not impair colony formation of two patient-derived glioma lines that express only the wild-type IDH1 allele (TS676 and TS516) (Fig. 1F), further supporting the selectivity of AGI-5198.; Reference: Science. 2013 May 3;340(6132):626-30. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23558169/
• In Vivo Activity: The effects of orally administered AGI-5198 on the growth of human glioma xenografts were examined. When given daily to mice with established R132H-IDH1 glioma xenografts, AGI-5198 [450 mg per kg of weight (mg/kg) per os] caused 50 to 60% growth inhibition (Fig. 2A). Treatment was tolerated well with no signs of toxicity during 3 weeks of daily treatment (fig. S3). Tumors from AGI-5198- treated mice showed reduced staining with an antibody against the Ki-67 protein, a marker used for quantification of tumor cell proliferation in human brain tumors. In contrast, staining with an antibody against cleaved caspase-3 showed no differences between tumors from vehicle and AGI-5198-treated mice (fig. S4), suggesting that the growth-inhibitory effects of AGI-5198 were primarily due to impaired tumor cell proliferation rather than induction of apoptotic cell death. AGI-5198 did not affect the growth of IDH1 wild-type glioma xenografts (Fig. 2B).; Reference: Science. 2013 May 3;340(6132):626-30. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23558169/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).