Berzosertib

SKU: orb1701146

Description

Berzosertib (VE-822) is a potent and selective ATR inhibitor (Ki<0.2 nM) with additional activity against ATM (Ki=34 nM). It has demonstrated antitumor efficacy in preclinical models and is under clinical investigation for various solid tumors, including ovarian and advanced solid malignancies, in both in vitro and in vivo studies.

Research Area

Molecular Biology, Signal Transduction

Key Properties

• CAS Number: 1232416-25-9
• MW: 463.55
• Purity: 97.34% (May vary between batches)
• Formula: C₂₄H₂₅N₅O₃S
• SMILES: CNCc1ccc(cc1)-c1cc(on1)-c1nc(cnc1N)-c1ccc(cc1)S(=O)(=O)C(C)C
• Target: ATM/ATR
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.31 mM);DMSO:28 mg/mL (60.4 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  ATM:34 nM (Ki)|ATR:19 nM|PI3Kγ:220 nM (Ki)
• In Vivo:
  METHODS: To assay antitumor activity in vivo, Nude mice bearing PSN-1 xenografts were treated with Berzosertib (60 mg/kg, once daily by gavage) and XRT (6 Gy, once) for six days. RESULTS: Berzosertib alone had no effect on tumor growth, but XRT plus Berzosertib administered for six or four days more than doubled the TV600 of XRT alone.
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• In Vitro:
  METHODS: Human pancreatic cancer cells PSN-1 and MiaPaCa-2 were treated with Berzosertib (80 nmol/L) and gemcitabine (100 nM), XRT (6 Gy), and the expression levels of target proteins were detected by Western Blot. RESULTS: Berzosertib reduced phosphorylated Ser345-Chk1. Berzosertib did not inhibit ATM, Chk2 or DNA-PK phosphorylation in response to radiation, which further supports the selectivity of Berzosertib for ATR. METHODS: Osteosarcoma cells MNNG/HOS and 143B were treated with Berzosertib (0-100 µM) for 48 h. Cell viability was measured by MTT assay. RESULTS: Berzosterib caused a dose-dependent decrease in MNNG/HOS and 143B cell viability.
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• Cell Research:
  VE-822 is dissolved in DMSO and stored, and then diluted with appropriate media before use. Gemcitabine (10 nM) is added 24 h pre-XRT and is replaced with fresh medium before addition of VE-822. PSN-1 cells are treated with 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.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Berzosertib, ATR, ATM, VX-970, VX970, VE822, VE-822, VE 822, VX 970

Compound Identifiers

PubChem CID

59472121