| CAS NO: | 1232416-25-9 |
| 规格: | ≥98% |
| Molecular Weight (MW) | 463.55 |
|---|---|
| Formula | C24H25N5O3S |
| CAS No. | 1232416-25-9 |
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Solubility (In vitro) | DMSO: 36 mg/mL (77.66 mM) |
| Water: <1 mg/mL | |
| Ethanol: <1 mg/mL | |
| Other info | Chemical Name: 5-(4-(isopropylsulfonyl)phenyl)-3-(3-(4-((methylamino)methyl)phenyl)isoxazol-5-yl)pyrazin-2-amine. InChi Key: JZCWLJDSIRUGIN-UHFFFAOYSA-N InChi Code: InChI=1S/C24H25N5O3S/c1-15(2)33(30,31)19-10-8-18(9-11-19)21-14-27-24(25)23(28-21)22-12-20(29-32-22)17-6-4-16(5-7-17)13-26-3/h4-12,14-15,26H,13H2,1-3H3,(H2,25,27) SMILES Code: NC1=NC=C(C2=CC=C(S(=O)(C(C)C)=O)C=C2)N=C1C3=CC(C4=CC=C(CNC)C=C4)=NO3 |
| Synonyms | VE822; VE-822; VE 822; M6620; M-6620; M 6620; VX970; VX-970; VX 970 |
| In Vitro | In vitro activity: VE-822 (80 nM) attenuates ATR signaling pathway and reduces survival in tumor cells in response to XRT and gemcitabine. VE-822 (80 nM) attenuates ATR signaling in normal cells without enhancing radiation and gemcitabine killing in normal cells. VE-822 (80 nM) increases XRT-induced residual γH2AX and 53BP1 foci compared with XRT in MiaPaCa-2 and PSN-1 cells. VE-822 (80 nM) pre-treatment decreases Rad51 foci after XRT in MiaPaCa-2 and PSN-1 cells. VE-822 (80 nM) alone increases the G1-phase-fraction in MiaPaCa-2 and PSN-1 cells. VE-822 (80 nM) abrogates XRT enriched G2/M-phase-fraction in MiaPaCa-2 and PSN-1 cells. VE-822 has little effect alone, while VE-822 (80 nM) combined with XRT and/or gemcitabine enhances early and late apoptosis in PSN-1 cells that is strongest in the triple combination. VE-822 increases tumor response to DNA damaging agents associated with blockade of pChk1 Ser345. Kinase Assay: Berzosertib is an ATR inhibitor with a Ki value of less than 0.2 nM. It also inhibits ATM with a Ki of 34 nM. Cell Assay: NSC 613327 (10 nM) is added 24 h pre-XRT and is replaced with fresh medium before addition of Berzosertib (VE-822). PSN-1 cells are treated with Berzosertib (VE-822) (80 nM) for 1 h before, through to 18 h after, XRT (6 Gy). Apoptosis is analyzed 48 h after XRT by flow cytometry using an Annexin V-FITC kit with P. |
|---|---|
| In Vivo | VE-822 (60 mg/kg) inhibits phospho-Ser-345-Chk1 in mice bearing PSN-1 tumors after DNA-damaging agents. VE-822 (60 mg/kg) combined with XTR doubles the time for tumors to grow to 600 mm3 of XRT alone in mice bearing both PSN-1 and MiaPaCa-2 tumors. VE-822 (60 mg/kg) added to the combination of gemcitabine and XRT substantially prolongs the tumor growth delay compared with the Gem+XRT1 group n mice bearing both PSN-1 tumors. VE-822 (60 mg/kg) combined with XRT1 increases uptake in tumors by 44% compared with XRT1, suggesting that addition of VE-822 increased γH2AX phosphorylation and persistence of DNA damage caused by XRT. |
| Animal model | Mice bearing PSN-1 or MiaPaCa-2 tumors |
| Formulation & Dosage | Dissolved in saline; 60 mg/kg; Oral administration |
| References | Cell Death Dis. 2012 Dec 6;3:e441. |
m.cnreagent.com