WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406264
CAS#: 1355326-35-0
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.
MedKoo Cat#: 406264
Name: AGI-5198
CAS#: 1355326-35-0
Chemical Formula: C27H31FN4O2
Exact Mass: 462.2431
Molecular Weight: 462.55904
Elemental Analysis: C, 70.11; H, 6.76; F, 4.11; N, 12.11; O, 6.92
Synonym: AGI5198; AGI-5198; AGI 5198; IDHC35; IDH-C35; IDH C35.
IUPAC/Chemical Name: N-cyclohexyl-2-(N-(3-fluorophenyl)-2-(2-methyl-1H-imidazol-1-yl)acetamido)-2-(o-tolyl)acetamide
InChi Key: FNYGWXSATBUBER-UHFFFAOYSA-N
InChi Code: 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)
SMILES Code: O=C(NC1CCCCC1)C(N(C2=CC=CC(F)=C2)C(CN3C=CN=C3C)=O)C4=CC=CC=C4C
Appearance: white to off-white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: 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.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | AGI-5198 (IDH-C35) is a potent and selective mutant IDH1R132H inhibitor with an IC50 of 0.07 μM. |
| 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/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 24.0 | 51.89 | |
| Ethanol | 14.0 | 30.27 |
The following data is based on the product molecular weight 462.55904 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| In vitro protocol: | 1. Rohle D, Popovici-Muller J, Palaskas N, Turcan S, Grommes C, Campos C, Tsoi J, Clark O, Oldrini B, Komisopoulou E, Kunii K, Pedraza A, Schalm S, Silverman L, Miller A, Wang F, Yang H, Chen Y, Kernytsky A, Rosenblum MK, Liu W, Biller SA, Su SM, Brennan CW, Chan TA, Graeber TG, Yen KE, Mellinghoff IK. An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science. 2013 May 3;340(6132):626-30. doi: 10.1126/science.1236062. Epub 2013 Apr 4. PMID: 23558169; PMCID: PMC3985613. |
| In vivo protocol: | 1. Rohle D, Popovici-Muller J, Palaskas N, Turcan S, Grommes C, Campos C, Tsoi J, Clark O, Oldrini B, Komisopoulou E, Kunii K, Pedraza A, Schalm S, Silverman L, Miller A, Wang F, Yang H, Chen Y, Kernytsky A, Rosenblum MK, Liu W, Biller SA, Su SM, Brennan CW, Chan TA, Graeber TG, Yen KE, Mellinghoff IK. An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science. 2013 May 3;340(6132):626-30. doi: 10.1126/science.1236062. Epub 2013 Apr 4. PMID: 23558169; PMCID: PMC3985613. |
1: Kim J, DeBerardinis RJ. Cancer. Silencing a metabolic oncogene. Science. 2013 May 3;340(6132):558-9. doi: 10.1126/science.1238523. PubMed PMID: 23641103.
ML-309 , a Me-Too version of AGI-5198 is recently added in our website. Their chemical structures are compared side-by-side as the following:
