AZ6102

SKU: orb1300484

Description

AZ6102 is a highly selective small molecule inhibitor of TNKS1 and TNKS2, demonstrating potent inhibition of the Wnt signaling pathway with an IC50 of 5 nM in DLD-1 cells. It exhibits >100-fold selectivity over other PARP family members, making it a valuable chemical probe for studying Wnt-driven cancers in both cellular and animal models.

Research Area

Epigenetics & Chromatin, Molecular Biology, Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 1645286-75-4
• MW: 428.53
• Purity: 99.91% (May vary between batches)
• Formula: C₂₅H₂₈N₆O
• SMILES: C[C@H]1CN(C[C@@H](C)N1)c1cc(C)c(cn1)-c1ccc(cc1)-c1nc2n(C)ccc2c(=O)[nH]1
• Target: PARP,Wnt/beta-catenin
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.67 mM);DMSO:21.4 mg/mL (49.94 mM)

Bioactivity

• Target IC50:
  PARP1:2 μM|TNKS2:5 nM|TNKS1:5 nM|PARP2:0.5 μM
• In Vivo:
  Nude mice are administered 25 mg/kg of AZ-6102. The compound has a half-life of 4 hours and a CL of 24 mL/min.kg. Further analysis in mouse and rats shows that AZ-6102 has a moderate bioavailability at 12% and 18%, respectively. Western blot analysis for TNKS1, TNSK2 and Axin2 of treated DLD-1 cells shows that AZ-6102 had qualitatively stronger and longer lasting stabilization of TNSK1, TNSK2 and Axin2 than XAV-939 at lower concentrations (at 24, 48 and 72h). AZ-6102 has good pharmacokinetics in preclinical species with low Caco2 efflux (to avoid possible tumor resistance mechanisms). In addition, the compound can be formulated in a clinically relevant intravenous solution at 20 mg/mL using SBECD as an excipient at pH4. The results of AZ-6102 used as an i.v. probe compound to explore the in vivo effects of the inhibition of TNKS1 and TNSK2 on tumor xenografts and normal tissue are forthcoming.
• In Vitro:
  AZ6102 inhibits TNKS1 and TNKS2 in enzymatic assays and TCF4 reporter assays (<5 nM). AZ6102 inhibits proliferation of Colo320DM (GI50 ~40 nM), but has no anti-proliferative activity in the β-catenin mutant cell line HCT-116, or the BRCA mutant cell line MDA-MB-436. In Colo320DM, AZ6102 stabilizes axin2 protein and modulates Wnt target genes in a dose and time dependent manner both in vitro and in vivo.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

betacatenin, beta-catenin, AZ 6102, AZ6102, AZ-6102, bcatenin, PARP, inhibit, Inhibitor, Wnt/betacatenin, Wnt, Wnt/b-catenin, Wnt/β-catenin, poly ADP ribose polymerase, TNKS1, TNKS2, βcatenin

Compound Identifiers

PubChem CID

135905416