ETP46464

SKU: orb1226497

Description

ETP-46464 is a potent and selective inhibitor of ATR with IC50 of 25 nM.

Key Properties

• CAS Number: 1345675-02-6
• MW: 470.52
• Purity: >98% (HPLC)
• Formula: C₃₀H₂₂N₄O₂
• SMILES: N#CC(C)(C)C1=CC=C(N(C2=C3C=NC4=CC=C(C5=CC6=CC=CC=C6N=C5)C=C24)C(OC3)=O)C=C1
• Target: ATM/ATR
• Solubility: DMSO: 6 mg/mL (12.75 mM)

Bioactivity

• In Vitro:
  ETP-46464 (ATRi) also inhibits DNA-PK, PI3Kα and ATM with IC50s of 36 nM, 170 nM and 545 nM, respectively. Platinum-sensitive and -resistant ovarian, endometrial and cervical cancer cell lines are treated with varying levels of Cisplatin (0-50 μM) with or without the ETP-46464 (5.0 μM) and/or the KU55933 (10.0 μM) for 72 h. Single-agent dose response analyses of ETP-46464 and KU55933 in a subset of cell lines reveal a wide LD50 range of 10.0±8.7 and 38.3±7.6 μM respectively. Co-treatment doses are chosen based on these studies and previously published evidence of phospho-Chk1 (Ser345) and phospho-ATM (Ser1981) inhibition following ionizing radiation exposure and dose response treatments with ETP-46464 and KU55933. Treatment with ETP-46464 significantly increases the response of Cisplatin in all cell lines tested, resulting in 52-89% enhancement in activity and are synergistic. The combined inhibition of ATR and ATM enhances the response of Cisplatin to a level equivalent to that observed using ETP-46464 alone. These effects are independent of p53 status, and are observed in all gynecologic (GYN) cancer cells tested. Treatment with ETP-46464, but not KU55933, not only sensitizes these GYN cancer cell lines to Cisplatin, but also enhances the response of Carboplatin.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

ATM Inhibitor III | ATR Inhibitor III

Quick Database Links

Gene Symbol

ATM/ATR