1232416-25-9
1232416-25-9 structure
- Name: Berzosertib (VE-822)
- Chemical Name: 3-[3-[4-(methylaminomethyl)phenyl]-1,2-oxazol-5-yl]-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine
- CAS Number: 1232416-25-9
- Molecular Formula: C24H25N5O3S
- Molecular Weight: 463.552
- Catalog: Biochemical Inhibitor DNA damage ATM/ATR inhibitor
- Create Date: 2017-01-20 21:40:00
- Modify Date: 2024-01-02 20:02:47
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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.
| Name | 3-[3-[4-(methylaminomethyl)phenyl]-1,2-oxazol-5-yl]-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine |
|---|---|
| Synonyms |
5-(4-(isopropylsulfonyl)phenyl)-3-(3-(4-((methylamino)methyl)phenyl)isoxazol-5-yl)pyrazin-2-amine
5-[4-(Isopropylsulfonyl)phenyl]-3-(3-{4-[(methylamino)methyl]phenyl}-1,2-oxazol-5-yl)-2-pyrazinamine VE-822 UNII:L423PRV3V3 VX-970 2-Pyrazinamine, 3-[3-[4-[(methylamino)methyl]phenyl]-5-isoxazolyl]-5-[4-[(1-methylethyl)sulfonyl]phenyl]- Berzosertib |
| 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. |
|---|---|
| Related Catalog | |
| 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. |
| References |
| Density | 1.3±0.1 g/cm3 |
|---|---|
| Boiling Point | 674.4±55.0 °C at 760 mmHg |
| Molecular Formula | C24H25N5O3S |
| Molecular Weight | 463.552 |
| 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 |
| Index of Refraction | 1.603 |
| Storage condition | -20℃ |