1432660-47-3
1432660-47-3 structure
- Name: AGI-6780
- Chemical Name: 1-[5-(cyclopropylsulfamoyl)-2-thiophen-3-ylphenyl]-3-[3-(trifluoromethyl)phenyl]urea
- CAS Number: 1432660-47-3
- Molecular Formula: C21H18F3N3O3S2
- Molecular Weight: 481.511
- Catalog: Biochemical Inhibitor Metabolism Dehydrogenase inhibitor
- Create Date: 2017-10-26 23:25:35
- Modify Date: 2024-01-02 18:00:06
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AGI-6780 that potently and selectively inhibits the tumor-associated mutant IDH2R140Q with IC50 of 23±1.7 nM. AGI-6780 is less potent against IDH2WT with IC50 of 190±8.1 nM.
| Name | 1-[5-(cyclopropylsulfamoyl)-2-thiophen-3-ylphenyl]-3-[3-(trifluoromethyl)phenyl]urea |
|---|---|
| Synonyms |
fd5013
Benzenesulfonamide, N-cyclopropyl-4-(3-thienyl)-3-[[[[3-(trifluoromethyl)phenyl]amino]carbonyl]amino]- N-Cyclopropyl-4-(3-thienyl)-3-({[3-(trifluoromethyl)phenyl]carbamoyl}amino)benzenesulfonamide agi 6780 qcr-283 AGI-6780 |
| Description | AGI-6780 that potently and selectively inhibits the tumor-associated mutant IDH2R140Q with IC50 of 23±1.7 nM. AGI-6780 is less potent against IDH2WT with IC50 of 190±8.1 nM. |
|---|---|
| Related Catalog | |
| Target |
IC50: 23±1.7 nM (IDH2R140Q), 190±8.1 nM (IDH2WT)[1] |
| In Vitro | AGI-6780 is tested in both human glioblastoma U87 and TF-1 cells expressing IDH2R140Q, as well as against IDH1R132H for 48 h incubation, with IC50 of 11±2.6 nM, 18±0.51 nM, and >1 mM, respectivly.Treatment of TF-1R140Q cells with AGI-6780, at concentrations that lower 2HG to near-normal physiologic levels, restore expression of both HBG and KLF1 genes and the color change associated with differentiation. AGI-6780 can reverse the IDH2R140Q-induced differentiation block in TF-1 cells. Pretreatment with AGI-6780 (0.2 μM and 1 μM) markedly decreased the intracellular concentration of (R)-2-hydroxyglutarate in the TF1R140Q cells and restored their ability to undergo EPO-induced differentiation[1]. |
| Kinase Assay | AGI-6780 is prepared as 10 mM stock in DMSO and diluted to 50X final concentration in DMSO, for a 50 μL reaction mixture. IDH enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate is measured using a NADPH depletion assay. In the assay the remaining cofactor is measured at the end of the reaction with the addition of a catalytic excess of diaphorase and resazurin, to generate a fluorescent signal in proportion to the amount of NADPH remaining. IDH enzyme activity in the direction of isocitrate to alpha-ketoglutarate conversion is measured by direct coupling of the NADPH production to conversion of resazurin to resorufin by diaphorase. In both cases, resorufin is measured fluorometrically at Ex544 Em590[1]. |
| Cell Assay | Cells are sorted from fresh or frozen bone marrow aspirates and blood samples after labelling with PE-CD34, APC-CD38, PE-CD14, FITC-CD3 (clone HIT3a) and PECy7-CD19 (clone SJ25C1) antibodies using a MoFlow cell sorter. Unfractionated nucleated blood or bone marrow cells are plated in Methocult H4434 methylcellulose medium at 104 cells/dish, in duplicate dishes per condition. AGI-6780 (5 mM) is directly added to the medium. Dishes are incubated in a humidified incubator at 37°C and colonies containing at least 30 cells are counted after 13 days[1]. |
| References |
| Density | 1.5±0.1 g/cm3 |
|---|---|
| Molecular Formula | C21H18F3N3O3S2 |
| Molecular Weight | 481.511 |
| Exact Mass | 481.074158 |
| PSA | 127.41000 |
| LogP | 4.42 |
| Index of Refraction | 1.652 |
| Hazard Codes | Xi |
|---|---|
| RIDADR | NONH for all modes of transport |