Home
Products
Berzosertib (VE-822)
| Product Name | Berzosertib (VE-822) |
| Price: | Inquiry |
| Catalog No.: | CN00464 |
| CAS No.: | 1232416-25-9 |
| Molecular Formula: | C24H25N5O3S |
| Molecular Weight: | 463.55 g/mol |
| Purity: | >=98% |
| Type of Compound: | Alkaloids |
| Physical Desc.: | Powder |
| Source: | |
| Solvent: | Chloroform, Dichloromethane, Ethyl Acetate, DMSO, Acetone, etc. |
| SMILES: | CNCc1ccc(cc1)c1noc(c1)c1nc(cnc1N)c1ccc(cc1)S(=O)(=O)C(C)C |
| Contact us | |
|---|---|
| First Name: | |
| Last Name: | |
| E-mail: | |
| Question: | |
| Description | 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. |
| Target | ATR:0.2 nM (Ki) ATM:34 nM (Ki) PI3Kγ:220 nM (Ki) |
| 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 Gemcitabine (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 Gemcitabine 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), Gemcitabine (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]. |
| Cell Assay | Gemcitabine (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]. |
| Animal Admin | 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). Gemcitabine 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. |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 674.4±55.0 °C at 760 mmHg |
| Flash Point | 361.7±31.5 °C |
| Exact Mass | 463.167816 |
| PSA | 133.11000 |
| LogP | 3.36 |
| Vapour Pressure | 0.0±2.1 mmHg at 25°C |
| Storage condition | -20℃ |