| CAS |
No.1232416-25-9 |
| 英文名称 |
Berzosertib |
| 别名 |
VX970;M6620;VE-822 |
| 分子式 |
C24H25N5O3S |
| 分子量 |
463.55 |
| 溶解性 |
Soluble in DMSO ≥4mg/mL(Need ultrasonic) |
| 纯度 |
≥98% |
| 外观(性状) |
Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD27976794 |
| SMILES |
CC(C)S(=O)(=O)C1=CC=C(C=C1)C2=CN=C(C(=N2)C3=CC(=NO3)C4=CC=C(C=C4)CNC)N |
| InChIKey |
JZCWLJDSIRUGIN-UHFFFAOYSA-N |
| InChI |
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) |
| PubChem CID |
59472121 |
| 靶点 |
ATM/ATR |
| 通路 |
DNA Damage/DNA Repair; PI3K/Akt/mTOR |
| 背景说明 |
Berzosertib是一种 ATR 抑制剂，也可抑制 ATM。 |
| 生物活性 |
Berzosertib (VE-822) is an ATR inhibitor with a Ki value of less than 0.2 nM. It also inhibits ATM with a Ki of 34 nM.[1] |
| In Vitro |
Berzosertib (VE-822) also inhibits DNK-PA， mTOR， PI3Kγ with IC50 of >4， >1， and 0.22 μM， respectively. In PSN-1 and MiaPaCa-2 cells， Berzosertib (VE-822) inhibits ATR and ATM with IC50 of 19 nM and 2.6 μM， respectively. VE-822 (80 nM) reduces phospho-Ser345-Chk1 after NSC 613327 (100 nM)， radiation (XRT) (6 Gy) or both in PDAC. Additionally， Berzosertib (VE-822) does not inhibit ATM， Chk2 or DNA-PK phosphorylation in response to radiation， which further supports the selectivity of Berzosertib (VE-822) for ATR. VE-822 decreases survival of irradiated PDAC (all lines used are p53-mutant; K-Ras mutant). Knock down of Chk1 by siRNA sensitizes PSN-1 and MiaPaCa-2 cells to radiation but the radiosensitising effect is less profound compare with Berzosertib (VE-822). Adding Berzosertib (VE-822) to NSC 613327 reduces survival ~2-3-fold and dramatically more after chemoradiotherapy[1]. |
| In Vivo |
PSN-1 xenografts are treated with Berzosertib (VE-822) (60 mk/kg; d0， 1)， NSC 613327 (100 mg/kg; d0) and/or XRT (6 Gy; d1). Tumors are then harvested 2 h post-XRT. Berzosertib (VE-822) inhibits p-Ser-345-Chk1 in xenografts after DNA-damaging agents， establishing VE-822 as a potent inhibitor of ATR in vivo. Besides， Berzosertib (VE-822) enhances the therapeutic efficacy of radiation (XRT) in MiaPaCa-2 and PSN-1 xenograft models[1]. |
| 细胞实验 |
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 PI[1]. |
| 动物实验 |
Mice[1] MiaPaCa-2 cells and PSN-1 cells (106 in 50 μL serum-free medium mixed with 50 μL of Matrigel) are inoculated subcutaneously in female Balb/c nude mice. When the xenograft tumors reach 80 mm3， the mice are randomized. Berzosertib (VE-822) (60 mg/kg) is administered by oral gavage on one of three alternate schedules; either daily on days 0-5 (total of six days dosing)， daily on days 0 through to 3 (total of 4 days dosing) or on days 1， 3 and 5. XRT (6 Gy) is given either on days 0 or 1 or days 1-5 (total of 5 days dosing; 2 Gy). NSC 613327 is dosed at 100 mg/kg by intraperitoneal injection on day 0. XRT to the tumor is given 2 h after initiation of Berzosertib (VE-822) treatment. |
| 数据来源文献 |
[1]. Fokas E， et al. Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis. 2012 Dec 6;3:e441. |
| 规格 |
5mg 10mg 50mg 100mg |
| 单位 |
瓶 |
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