ABT-737

SKU: orb1223852

Description

A BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w with EC50 of 78.7 nM, 30.3 nM and 197.8 nM in cell-free assays, respectively; shows no inhibition against Mcl-1, Bcl-B or Bfl-1; induces the disruption of the BCL-2/BAX complex and BAK-dependent but BIM-independent activation of the intrinsic apoptotic pathway; exhibits single-agent-mechanism-based killing of cells from lymphoma and small-cell lung carcinoma lines, as well as primary patient-derived cells, and in animal models.Ovarian Cancer Phase 2 Clinical.

Key Properties

• CAS Number: 852808-04-9
• MW: 813.4269
• Purity: >98% (HPLC)
• Formula: C₄₂H₄₅ClN₆O₅S₂
• SMILES: O=C(NS(=O)(C1=CC=C(N[C@H](CCN(C)C)CSC2=CC=CC=C2)C([N+]([O-])=O)=C1)=O)C3=CC=C(N4CCN(CC5=CC=CC=C5C6=CC=C(Cl)C=C6)CC4)C=C3
• Target: Bcl-2
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  ABT-737 (20, 30 mg/kg/day; i.p.; for 21 days) suppresses the leukemia burden by 48% and 53% at the 20 and 30 mg/kg dose levels, respectively, in four-to six-week-old CB. 17 Scid mice with human leukemia KG-1 cells. ABT-737 significantly extends survival of mice in this aggressive leukemia model.
• In Vitro:
  ABT-737 binds BCL-2, BCL-XL, and BCL-W with high affinity (Ki<1 nM) but binds weakly (Ki>460 nM) to other antiapoptotic BCL-2 family members, including MCL-1 and BFL-1. ABT-737 binds the BH3-binding groove of BCL-XL and BCL-2. ABT-737 (100 nM; 1-72 hours) induces apoptosis and synergizes with chemotherapy in HL-60 cells. ABT-737 (5, 7.5, 10 μM; 72 hours) causes approximately 80% HCT116 cell death. The BAX knockout variant is completely resistant to ABT-737. ABT-737 has no effect on cell cycle distribution. ABT-737 disrupts BCL-2/BAX heterodimerization and induces BAX conformational change in HL-60 leukemic cells. ABT-737 induces a BAX/BAK-dependent impairment of maximal O2 consumption rate in sensitive cells. Stable BCL-2 overexpression in MCF10A cells induces an ABT-737-sensitive primed for death state. ABT-737 induces dose-dependent impairment of maximal O2 consumption rate in B-cell lymphoma cells.

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

ABT737 | ABT 737

Quick Database Links

Gene Symbol

Bcl-2