AGI-5198
AGI-5198 is a selective R132H-IDH1 inhibitor which is identified through a high-throughput screen blocked, in a dose-dependent manner, the ability of the mutant enzyme (mIDH1) to produce R-2-hydroxyglutarate (R-2HG). It is also induced the expression of zinc finger and BTB domain–containing protein 16 (ZBTB16), known as promyelocytic leukemia zinc finger (PLZF), a transcriptional repressor protein which is located on chromosome 11q23 and has been shown to promote glial differentiation in the central nervous system. AGI-5198 is also able to induce the expression of genes and cell markers associated with glial-specific differentiation in glioma cell, the expression of differentiation-associated genes, reduce H3K9 trimethylaytion, and cause tumor growth inhibition.
Reference
Dan Rohle, Janeta Popovici-Muller, Nicolaos Palaskas, Sevin Turcan, Christian Grommes, Carl Campos, Jennifer Tsoi, Owen Clark, Barbara Oldrini, Evangelia Komisopoulou, Kaiko Kunii, Alicia Pedraza, Stefanie Schalm, Lee Silverman, Alexandra Miller, Fang Wang, Hua Yang, Yue Chen, Andrew Kernytsky, Marc K. Rosenblum, Wei Liu, Scott A. Biller, Shinsan M. Su, Cameron W. Brennan, Timothy A. Chan, Thomas G. Graeber, Katharine E. Yen, Ingo K. Mellinghoff. An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells. Science 340, 626 (2013)
Francine E Garrett-Bakelman, Ari M Melnick. Differentiation therapy for IDH1/2 mutant malignancies. Cell Research (2013) 23:975–977.
| Storage | Store at -20°C |
| M.Wt | 462.56 |
| Cas No. | 1355326-35-0 |
| Formula | C27H31FN4O2 |
| Synonyms | AGI5198, AGI 5198 |
| Solubility | ≥23.15 mg/mL in DMSO, ≥18.17 mg/mL in EtOH with ultrasonic and warming, <2.3 mg/mL in H2O |
| Chemical Name | N-cyclohexyl-2-(3-fluoro-N-[2-(2-methylimidazol-1-yl)acetyl]anilino)-2-(2-methylphenyl)acetamide |
| SDF | Download SDF |
| Canonical SMILES | CC1=CC=CC=C1C(C(=O)NC2CCCCC2)N(C3=CC(=CC=C3)F)C(=O)CN4C=CN=C4C |
| Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. |
| Cell experiment [1]: | |
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Cell lines |
TS603 glioma cells with an endogenous heterozygous R132H-IDH1 mutation |
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Preparation method |
The solubility of this compound in DMSO is >23.2mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
20-3000 nM; 2 days |
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Applications |
In R132H-IDH1 mutant TS603 glioma cells, AGI-5198 inhibited R-2HG production and impaired soft-agar colony formation of IDH1-mutant TS603 glioma cells. |
| Animal experiment [1]: | |
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Animal models |
mice with established R132H-IDH1 glioma xenografts |
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Dosage form |
450 mg/kg; orally administered; 3 weeks of daily treatment |
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Application |
In mice with established R132H-IDH1 glioma xenografts, AGI-5198 (450 mg/kg) caused 50 to 60% growth inhibition. AGI-5198 was tolerated well with no signs of toxicity. The growth-inhibitory effects of AGI-5198 were primarily due to impaired tumor cell proliferation rather than induction of apoptotic cell death. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Dan Rohle, Janeta Popovici-Muller, Nicolaos Palaskas, Sevin Turcan, Christian Grommes, Carl Campos, Jennifer Tsoi, Owen Clark, Barbara Oldrini, Evangelia Komisopoulou, Kaiko Kunii, Alicia Pedraza, Stefanie Schalm, Lee Silverman, Alexandra Miller, Fang Wang, Hua Yang, Yue Chen, Andrew Kernytsky, Marc K. Rosenblum, Wei Liu, Scott A. Biller, Shinsan M. Su, Cameron W. Brennan, Timothy A. Chan, Thomas G. Graeber, Katharine E. Yen, Ingo K. Mellinghoff. An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells. Science 340, 626 (2013). | |
| Description | AGI-5198 is the first highly potent and selective inhibitor of IDH1 R132H/R132C mutants with IC50 of 0.07 μM/0.16 μM. | |||||
| Targets | R132H-IDH1 | R132C-IDH1 | ||||
| IC50 | 0.07 μM | 0.16 μM | ||||
Quality Control & MSDS
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Chemical structure
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Related Biological Data
