product name VE-821
Description: VE-821 is a potent and selective ATP competitive inhibitor of ATR with Ki/IC50 of 13 nM/26 nM in cell-free assays, it shows inhibition of H2AX phosphorylation, and had minimal activity against PIKKs ATM, DNA-PK, mTOR and PI3Kγ. VE-821 inhibited radiation- and gemcitabine-induced phosphorylation of Chk1, confirming inhibition of ATR signaling. Consistently, VE-821 significantly enhanced the sensitivity of PSN-1, MiaPaCa-2 and primary PancM pancreatic cancer cells to radiation and gemcitabine under both normoxic and hypoxic conditions.
References: Nat Chem Biol. 2011 Apr 13;7(7):428-30; J Med Chem. 2011 Apr 14;54(7):2320-30.
368.41
Formula
C18H16N4O3S
CAS No.
1232410-49-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 74 mg/mL (200.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
30% PEG400+0.5% Tween80+5% propylene glycol: 30 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19395210
| In Vitro |
In vitro activity: VE-821 shows excellent selectivity for ATR with minimal cross-reactivity against the related PIKKs ATM, DNA-PK, mTOR and PI3K (Kis of 16 μM, 2.2 μM, >1 μM and 3.9 μM, respectively. VE-821 alone commits a large fraction of cancer cell populations to death, but it only reversibly limits cell cycle progression in normal cells, with minimal death or long-term detrimental effects. VE-821 along with cisplatin treatment shows the most marked synergy. VE-821 inhibits H2AX cell growth with IC50 of 800 nM. Kinase Assay: The ability of compounds to inhibit ATR, ATM or DNAPK kinase activity istested using a radiometric-phosphate incorporation assay. A stock solution isprepared consisting of the appropriate buffer, kinase, and target peptide. To this isadded the compound of interest, at varying concentrations in DMSO to a final DMSO concentration of 7%. Assays are initiated by addition of an appropriate [γ-33P]ATP solution and incubated at 25 ℃. Assays are stopped, after the desired time course, by addition of phosphoric acid and ATP to a final concentration of 100 mM and 0.66μM, respectively. Peptides are captured on a phosphocellulose membrane, prepared as per manufacturers instructions, 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. Cell Assay: HFL1 cells were pretreated with 10 μM VE-821 or DMSO before addition of 200 μM cisplatin (Cis), 1 μM gemcitabine (Gem), 100 μM etoposide (Etop) or 5 Gy ionizing radiation (IR), VE-821 blocks Chk1 Ser345 phosphorylation under all conditions and inhibits H2AX phosphorylation in treatment with cisplatin and gemcitabine. In the H23 cancer cell line, VE-821 shows marked synergy with cisplatin in growth arrest. |
|---|---|
| In Vivo | |
| Animal model | |
| Formulation & Dosage | |
| References | Nat Chem Biol. 2011 Apr 13;7(7):428-30; J Med Chem. 2011 Apr 14;54(7):2320-30. |
Related Posts
product name VE-821
Description: VE-821 is a potent and selective ATP competitive inhibitor of ATR with Ki/IC50 of 13 nM/26 nM in cell-free assays, it shows inhibition of H2AX phosphorylation, and had minimal activity against PIKKs ATM, DNA-PK, mTOR and PI3Kγ. VE-821 inhibited radiation- and gemcitabine-induced phosphorylation of Chk1, confirming inhibition of ATR signaling. Consistently, VE-821 significantly enhanced the sensitivity of PSN-1, MiaPaCa-2 and primary PancM pancreatic cancer cells to radiation and gemcitabine under both normoxic and hypoxic conditions.
References: Nat Chem Biol. 2011 Apr 13;7(7):428-30; J Med Chem. 2011 Apr 14;54(7):2320-30.
368.41
Formula
C18H16N4O3S
CAS No.
1232410-49-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 74 mg/mL (200.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
30% PEG400+0.5% Tween80+5% propylene glycol: 30 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19395210
| In Vitro |
In vitro activity: VE-821 shows excellent selectivity for ATR with minimal cross-reactivity against the related PIKKs ATM, DNA-PK, mTOR and PI3K (Kis of 16 μM, 2.2 μM, >1 μM and 3.9 μM, respectively. VE-821 alone commits a large fraction of cancer cell populations to death, but it only reversibly limits cell cycle progression in normal cells, with minimal death or long-term detrimental effects. VE-821 along with cisplatin treatment shows the most marked synergy. VE-821 inhibits H2AX cell growth with IC50 of 800 nM. Kinase Assay: The ability of compounds to inhibit ATR, ATM or DNAPK kinase activity istested using a radiometric-phosphate incorporation assay. A stock solution isprepared consisting of the appropriate buffer, kinase, and target peptide. To this isadded the compound of interest, at varying concentrations in DMSO to a final DMSO concentration of 7%. Assays are initiated by addition of an appropriate [γ-33P]ATP solution and incubated at 25 ℃. Assays are stopped, after the desired time course, by addition of phosphoric acid and ATP to a final concentration of 100 mM and 0.66μM, respectively. Peptides are captured on a phosphocellulose membrane, prepared as per manufacturers instructions, 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. Cell Assay: HFL1 cells were pretreated with 10 μM VE-821 or DMSO before addition of 200 μM cisplatin (Cis), 1 μM gemcitabine (Gem), 100 μM etoposide (Etop) or 5 Gy ionizing radiation (IR), VE-821 blocks Chk1 Ser345 phosphorylation under all conditions and inhibits H2AX phosphorylation in treatment with cisplatin and gemcitabine. In the H23 cancer cell line, VE-821 shows marked synergy with cisplatin in growth arrest. |
|---|---|
| In Vivo | |
| Animal model | |
| Formulation & Dosage | |
| References | Nat Chem Biol. 2011 Apr 13;7(7):428-30; J Med Chem. 2011 Apr 14;54(7):2320-30. |