AZ6102 is a potent TNKS1/2 inhibitor that has 100-fold selectivity against other PARP family enzymes and shows IC50 of 5 nM for Wnt pathway inhibition in DLD-1 cells.
| Pack Size | Availability | Price/USD | Quantity |
|---|---|---|---|
| 2 mg | In stock | $ 76 | |
| 4 mg | In stock | $ 136 | |
| 8 mg | In stock | $ 190 | |
| 20 mg | In stock | $ 376 | |
| 40 mg | In stock | $ 594 |
| Description | AZ6102 is a potent TNKS1/2 inhibitor that has 100-fold selectivity against other PARP family enzymes and shows IC50 of 5 nM for Wnt pathway inhibition in DLD-1 cells. |
| Targets&IC50 | TNKS1:5 nM, TNKS2:5 nM |
| 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. |
| 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. |
| CAS No. | 1645286-75-4 |
| Chemical Formula | C25H28N6O |
| Molecular Weight | 428.54 |
| Solubility | DMSO: 21.4 mg/mL (50 mM) |
| Storage | Powder: -20°C for 2 years In solvent: -80°C for 1 year |
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