VE-821
VE-821 structure
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Common Name | VE-821 | ||
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| CAS Number | 1232410-49-9 | Molecular Weight | 368.410 | |
| Density | 1.4±0.1 g/cm3 | Boiling Point | 568.4±50.0 °C at 760 mmHg | |
| Molecular Formula | C18H16N4O3S | Melting Point | N/A | |
| MSDS | USA | Flash Point | 297.6±30.1 °C | |
Use of VE-821VE-821 is a potent ATP-competitive inhibitor of ATR with Ki/IC50 of 13 nM/26 nM. |
| Name | 3-amino-6-(4-methylsulfonylphenyl)-N-phenylpyrazine-2-carboxamide |
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| Synonym | More Synonyms |
| Description | VE-821 is a potent ATP-competitive inhibitor of ATR with Ki/IC50 of 13 nM/26 nM. |
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| Related Catalog | |
| Target |
ATR:13 nM (Ki) ATM:16 μM (Ki) DNA-PK:2.2 μM (Ki) PI3Kγ:3.9 μM (Ki) |
| In Vitro | VE-821 shows excellent selectivity for ATR with minimal cross-reactivity against the related PIKKs ATM, DNA-PK, mTOR and PI3Kγ (Kis of 16 μM, 2.2 μM, >1 μM and 3.9 μM, respectively) and against a large panel of unrelated protein kinases[1]. VE-821 (compound 27) also inhibits ATM and DNA-PK wirh IC50 of >8 μM, and 4.4 μM, respectively[2]. VE-821 significantly enhances the sensitivity of PSN-1, MiaPaCa-2 and primary PancM pancreatic cancer cells to radiation and Gemcitabine under both normoxic and hypoxic conditions. ATR inhibition by VE-821 leads to inhibition of radiation-induced G2/M arrest in cancer cells. In both PSN-1 and MiaPaCa-2 cells, 1 µM VE-821 inhibits phosphorylation of Chk1 (Ser 345) after treatment with Gemcitabine (100 nM), radiation (6 Gy) or both, at 2 h post-irradiation[3]. |
| Kinase Assay | The ability of compounds (e.g., VE-821) to inhibit ATR, ATM or DNAPK kinase activity is tested using a radiometric-phosphate incorporation assay. A stock solution is prepared consisting of the appropriate buffer, kinase, and target peptide. To this is added the compound of interest, at varying concentrations in DMSO to a final DMSO concentration of 7%. Assays are initiated by addition of an appropriate [g-33P]ATP solution and incubated at 25°C. Assays are stopped, after the desired time course, by addition of phosphoric acid and ATP to a final concentration of 100 mM and 0.66 μM, respectively. Peptides are captured on a phosphocellulose membrane, prepared, and washed six times with 200 μL of 100 mM phosphoric acid, prior to the addition of 100 μL of scintillation cocktail and scintillation counting on a 1450 Microbeta Liquid Scintillation Counter. Dose−response data are analyzed using GraphPad Prism software[2]. |
| Cell Assay | MiaPaCa-2, PSN-1 and Panc1 cells (5×104) are plated in 96-well plates and after 4 h treated with increasing concentrations of VE-821 at 1 h before irradiation with a single dose of 4 Gy. Medium is replaced 72 h post-irradiation at which point viability is measured using the using the Alamar Blue assay. Cells are allowed to proliferate and cell viability is again analyzed at day 10 for the different treatment conditions. Cell viability and surviving fraction are normalized to the untreated (control) group[3]. |
| References |
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Boiling Point | 568.4±50.0 °C at 760 mmHg |
| Molecular Formula | C18H16N4O3S |
| Molecular Weight | 368.410 |
| Flash Point | 297.6±30.1 °C |
| Exact Mass | 368.094299 |
| PSA | 126.91000 |
| LogP | 2.93 |
| Vapour Pressure | 0.0±1.6 mmHg at 25°C |
| Index of Refraction | 1.658 |
| Storage condition | -20°C |
| RIDADR | NONH for all modes of transport |
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~70%
VE-821 CAS#:1232410-49-9 |
| Literature: VERTEX PHARMACEUTICALS INCORPORATED; CHARRIER, Jean-Damien; DURRANT, Steven, John; KNEGTEL, Ronald, Marcellus Alphonsus; VIRANI, Aniza, Nizarali; REAPER, Philip, Michael Patent: WO2011/143425 A2, 2011 ; Location in patent: Page/Page column 37; 39 ; WO 2011/143425 A2 |
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VE-821 CAS#:1232410-49-9 |
| Literature: Journal of Medicinal Chemistry, , vol. 54, # 7 p. 2320 - 2330 |
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VE-821 CAS#:1232410-49-9 |
| Literature: Journal of Medicinal Chemistry, , vol. 54, # 7 p. 2320 - 2330 |
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VE-821 CAS#:1232410-49-9 |
| Literature: Journal of Medicinal Chemistry, , vol. 54, # 7 p. 2320 - 2330 |
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VE-821 CAS#:1232410-49-9 |
| Literature: Journal of Medicinal Chemistry, , vol. 54, # 7 p. 2320 - 2330 |
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VE-821 CAS#:1232410-49-9 |
| Literature: WO2011/143425 A2, ; WO 2011/143425 A2 |
| CS-0238 |
| VE-821 |
| VE 821 |
| 3-amino-6-(4-(methylsulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide |