AGI-5198IDH1 inhibitor against R132 mutant,selective and cell-permeable CAS# 1355326-35-0 |
- Mutant IDH1 inhibitor
Catalog No.:BCC4144
CAS No.:1429180-08-4
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 1355326-35-0 | SDF | Download SDF |
| PubChem ID | 56645356 | Appearance | Powder |
| Formula | C27H31FN4O2 | M.Wt | 462.56 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Synonyms | IDH-C35 | ||
| Solubility | DMSO : 7.14 mg/mL (15.44 mM; Need ultrasonic) | ||
| Chemical Name | N-cyclohexyl-2-(3-fluoro-N-[2-(2-methylimidazol-1-yl)acetyl]anilino)-2-(2-methylphenyl)acetamide | ||
| SMILES | CC1=CC=CC=C1C(C(=O)NC2CCCCC2)N(C3=CC(=CC=C3)F)C(=O)CN4C=CN=C4C | ||
| Standard InChIKey | FNYGWXSATBUBER-UHFFFAOYSA-N | ||
| Standard 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) | ||
| 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. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| 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 | ||||
AGI-5198 Dilution Calculator
AGI-5198 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.1619 mL | 10.8094 mL | 21.6188 mL | 43.2376 mL | 54.047 mL |
| 5 mM | 0.4324 mL | 2.1619 mL | 4.3238 mL | 8.6475 mL | 10.8094 mL |
| 10 mM | 0.2162 mL | 1.0809 mL | 2.1619 mL | 4.3238 mL | 5.4047 mL |
| 50 mM | 0.0432 mL | 0.2162 mL | 0.4324 mL | 0.8648 mL | 1.0809 mL |
| 100 mM | 0.0216 mL | 0.1081 mL | 0.2162 mL | 0.4324 mL | 0.5405 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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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.
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Radioprotection of IDH1-Mutated Cancer Cells by the IDH1-Mutant Inhibitor AGI-5198.[Pubmed:26363012]
Cancer Res. 2015 Nov 15;75(22):4790-802.
Isocitrate dehydrogenase 1 (IDH1) is mutated in various types of human cancer to IDH1(R132H), a structural alteration that leads to catalysis of alpha-ketoglutarate to the oncometabolite D-2-hydroxyglutarate. In this study, we present evidence that small-molecule inhibitors of IDH1(R132H) that are being developed for cancer therapy may pose risks with coadministration of radiotherapy. Cancer cells heterozygous for the IDH1(R132H) mutation exhibited less IDH-mediated production of NADPH, such that after exposure to ionizing radiation (IR), there were higher levels of reactive oxygen species, DNA double-strand breaks, and cell death compared with IDH1 wild-type cells. These effects were reversed by the IDH1(R132H) inhibitor AGI-5198. Exposure of IDH1 wild-type cells to D-2-hydroxyglutarate was sufficient to reduce IDH-mediated NADPH production and increase IR sensitivity. Mechanistic investigations revealed that the radiosensitivity of heterozygous cells was independent of the well-described DNA hypermethylation phenotype in IDH1-mutated cancers. Thus, our results argue that altered oxidative stress responses are a plausible mechanism to understand the radiosensitivity of IDH1-mutated cancer cells. Further, they offer an explanation for the relatively longer survival of patients with IDH1-mutated tumors, and they imply that administration of IDH1(R132H) inhibitors in these patients may limit irradiation efficacy in this setting.
