A-966492

SKU: orb1300831

Description

A-966492

Research Area

Epigenetics & Chromatin, Molecular Biology

Key Properties

• CAS Number: 934162-61-5
• MW: 324.35
• Purity: 99.27%
• Formula: C₁₈H₁₇FN₄O
• SMILES: NC(=O)c1cccc2[nH]c(nc12)-c1ccc(cc1F)[C@@H]1CCCN1
• Target: PARP
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (3.08 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);Ethanol:< 1 mg/mL (insoluble or slightly soluble);DMSO:8.13 mg/mL (25.07 mM)

Bioactivity

• Target IC50:
  PARP1:1 nM(ki)|PARP2:1.5 nM(Ki)
• In Vivo:
  A-966492 exhibits robust in vivo efficacy, particularly when used in combination with temozolomide (TMZ) in a B16F10 subcutaneous murine melanoma model and carboplatin in an MX-1 breast cancer xenograft model, alongside demonstrating effectiveness as a Single agent in a BRCA1-deficient MX-1 tumor model. This compound also showcases excellent pharmaceutical properties, achieving oral bioavailabilities between 34−72% and half-lives of 1.7−1.9 hours in Sprague Dawley rats, beagle dogs, and cynomolgus monkeys. furthermore , A-966492 significantly enhance the efficacy of TMZ in a murine B16F10 syngeneic melanoma model, with combination therapy groups showing superior efficacy.
• In Vitro:
  A-966492 s and out as a highly potent inhibitor of PARP, demonstrating exceptional efficacy agains the PARP-1 enzyme with a Kiof 1 nM and an EC50 of 1 nM in whole-cell assays. It markedly boost the effectiveness of TMZ in a dose-dependent fashion. Additionally, A-966492 exhibits oral bioavailability in various species, can travers the blood−brain barrier, and seems to infiltrate tumor tissues effectively. Representing a promising benzimidazole analogue with structural diversity, A-966492 is currently undergoing further preclinical characterization.
• Cell Research:
  C41 cells are treated with A-966492 for 30 minutes in a 96-well plate. PARP are activated by damaging DNA with 1 mM Water2 for 10 minutes. Cells are washed with ice-cold phosphate-buffered saline (PBS) once and fixed with prechilled methanol/acetone (7:3) at -20 °C for 10 minutes. After they are air-dried, plates are rehydrated with PBS and blocked using 5% nonfat dry milk in PBS-Tween(0.05%) (blocking solution) for 30 minutes at room temperature. Cells are incubated with anti-PAR antibody 1 h (1:50) in blocking solution at room temperature for 60 minutes followed by washing with PBS-Tween20 five times, and incubation with goat antimouse fluorescein 5(6)-isothiocyanate (FITC)-coupled antibody (1:50) and 1 μg mL 40,6-diamidino-2-phenylindole (DAPI) in blocking solution at room temperature for 60 minutes. After washing with PBS-Tween20 5 times, analysis is performed using an fmax Fluorescence Microplate Reader set a the excitation and emission wavelength for FITC o the excitation and emission wavelength for DAPI. PARP activity (FITC signal) is normalized with cell numbers (DAPI).(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

A966492, A-966492, A 966492, PARP2, PARP1, PARP, inhibit, Inhibitor, poly ADP ribose polymerase

Compound Identifiers

PubChem CID

16666333