AGI-6780IDH2/R140Q mutation inhibitor CAS# 1432660-47-3 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 1432660-47-3 | SDF | Download SDF |
| PubChem ID | 71299339 | Appearance | Powder |
| Formula | C21H18F3N3O3S2 | M.Wt | 481.51 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 29 mg/mL (60.23 mM) H2O : < 0.1 mg/mL (insoluble) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | 1-[5-(cyclopropylsulfamoyl)-2-thiophen-3-ylphenyl]-3-[3-(trifluoromethyl)phenyl]urea | ||
| SMILES | C1CC1NS(=O)(=O)C2=CC(=C(C=C2)C3=CSC=C3)NC(=O)NC4=CC=CC(=C4)C(F)(F)F | ||
| Standard InChIKey | CCAWRGNYALGPQH-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C21H18F3N3O3S2/c22-21(23,24)14-2-1-3-16(10-14)25-20(28)26-19-11-17(32(29,30)27-15-4-5-15)6-7-18(19)13-8-9-31-12-13/h1-3,6-12,15,27H,4-5H2,(H2,25,26,28) | ||
| 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-6780 is a potent and time-dependent inhibitor of IDH2-R140Q with IC50 values of 23±1.7 nM and 190±8.1 nM for IDH2-R140Q and IDH2-WT,respectively. | |||||
| Targets | IDH2-R140Q | IDH2-WT | ||||
| IC50 | 23±1.7 nM | 190±8.1 nM | ||||
AGI-6780 Dilution Calculator
AGI-6780 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.0768 mL | 10.384 mL | 20.768 mL | 41.536 mL | 51.92 mL |
| 5 mM | 0.4154 mL | 2.0768 mL | 4.1536 mL | 8.3072 mL | 10.384 mL |
| 10 mM | 0.2077 mL | 1.0384 mL | 2.0768 mL | 4.1536 mL | 5.192 mL |
| 50 mM | 0.0415 mL | 0.2077 mL | 0.4154 mL | 0.8307 mL | 1.0384 mL |
| 100 mM | 0.0208 mL | 0.1038 mL | 0.2077 mL | 0.4154 mL | 0.5192 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-6780 is a potent and selective inhibitor of tumor-associated IDH2/R140Q mutation with IC50 value of 23 nM [1].
AGI-6780 could significantly reduce intracellular concentration of 2HG in the human glioblastoma TF1/R140Q cells, as well as reverse IDH2/R140Q-mediated differentiation block in TF1 cells in the presence of EPO. AGI-6780 could restore KLF1 and hemoglobin G1/2 expressions in the EPO-induced TF1/R140Q cells [1].
References:
[1] Wang F1, Travins J, DeLaBarre B, Penard-Lacronique V, Schalm S, Hansen E, Straley K, Kernytsky A, Liu W, Gliser C, Yang H, Gross S, Artin E, Saada V,Mylonas E, Quivoron C, Popovici-Muller J, Saunders JO, Salituro FG, Yan S, Murray S, Wei W, Gao Y, Dang L, Dorsch M, Agresta S, Schenkein DP, Biller SA, Su SM, de Botton S, Yen KE. Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation. Science. 2013 May 3;340(6132):622-6.
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The Evolving Landscape in the Development of Isocitrate Dehydrogenase Mutant Inhibitors.[Pubmed:27292784]
Mini Rev Med Chem. 2016;16(16):1344-1358.
Isocitrate dehydrogenase (IDH) is a metabolic enzyme that converts isocitrate to alpha-ketoglutarate (alpha-KG). Genetic gain-of-function mutations in IDH1 and IDH2 confer a neomorphic activity that allow reduction of alpha -KG to (R)-2- hydroxyglutarate, the accumulation of which results in the development of cancers like low grade gliomas and leukemia. After treatment with AG-221 in clinical trials, a first-in-class inhibitor of mutated IDH2, 29 patients with acute myeloid leukemia or myelodysplastic syndrome experience complete remissions and the overall response rate is 59/159 (37%). Thus, IDH mutants have become intriguing targets for cancer therapeutics. In addition to providing a brief summary of IDH mutations, this review describes known inhibitors with potential activities against IDH mutants such as AG-120, AG-221, AG-881 and AGI-6780. The evolving landscape of IDH mutant inhibitors provides us an outlook on the discovery of novel, safer, and more effective cancer treatment strategies.
Potential mitochondrial isocitrate dehydrogenase R140Q mutant inhibitor from traditional Chinese medicine against cancers.[Pubmed:24995286]
Biomed Res Int. 2014;2014:364625.
A recent research of cancer has indicated that the mutant of isocitrate dehydrogenase 1 and 2 (IDH1 and 2) genes will induce various cancers, including chondrosarcoma, cholangiocarcinomas, and acute myelogenous leukemia due to the effect of point mutations in the active-site arginine residues of isocitrate dehydrogenase (IDH), such as IDH1/R132, IDH2/R140, and IDH2/R172. As the inhibition for those tumor-associated mutant IDH proteins may induce differentiation of those cancer cells, these tumor-associated mutant IDH proteins can be treated as a drug target proteins for a differentiation therapy against cancers. In this study, we aim to identify the potent TCM compounds from the TCM Database@Taiwan as lead compounds of IDH2 R140Q mutant inhibitor. Comparing to the IDH2 R140Q mutant protein inhibitor, AGI-6780, the top two TCM compounds, precatorine and abrine, have higher binding affinities with target protein in docking simulation. After MD simulation, the top two TCM compounds remain as the same docking poses under dynamic conditions. In addition, precatorine is extracted from Abrus precatorius L., which represents the cytotoxic and proapoptotic effects for breast cancer and several tumor lines. Hence, we propose the TCM compounds, precatorine and abrine, as potential candidates as lead compounds for further study in drug development process with the IDH2 R140Q mutant protein against cancer.
Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiation.[Pubmed:23558173]
Science. 2013 May 3;340(6132):622-6.
A number of human cancers harbor somatic point mutations in the genes encoding isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2). These mutations alter residues in the enzyme active sites and confer a gain-of-function in cancer cells, resulting in the accumulation and secretion of the oncometabolite (R)-2-hydroxyglutarate (2HG). We developed a small molecule, AGI-6780, that potently and selectively inhibits the tumor-associated mutant IDH2/R140Q. A crystal structure of AGI-6780 complexed with IDH2/R140Q revealed that the inhibitor binds in an allosteric manner at the dimer interface. The results of steady-state enzymology analysis were consistent with allostery and slow-tight binding by AGI-6780. Treatment with AGI-6780 induced differentiation of TF-1 erythroleukemia and primary human acute myelogenous leukemia cells in vitro. These data provide proof-of-concept that inhibitors targeting mutant IDH2/R140Q could have potential applications as a differentiation therapy for cancer.
