| Description: |
MN-64 is a potent tankyrase 1 inhibitor, with IC50s of 6 nM, 72 nM, 19.1 μM, and 39.4 μM for TNKS1, TNKS2, ARTD1 and ARTD2, respectively. |
| Target: |
TNKS1:6 nM (IC50)
TNKS2:72 nM (IC50)
ARTD1:19.1 μM (IC50)
ARTD2:39.4 μM (IC50) |
| In Vitro: |
MN-64 is a potent tankyrase 1 inhibitor, with IC50s of 6 nM, 72 nM, 19.1 μM, 39.4 μM for TNKS1, TNKS2, ARTD1 and ARTD2, respectively. MN-64 effectively inhibits Wnt/β-catenin at 1 μM, and blocks STF luciferase activity at 200 nM[1]. |
| Kinase Assay: |
Inhibitory potency of compounds on Tankyrase-1 enzymatic activity is evaluated using a Scintillation Proximity Assay (SPA). The assay is designed to measure compound inhibition of Tankyrase-1 autoPARsylation (Tankyrase-1 is both enzyme and substrate in this assay). Truncated recombinant human Tankyrase-1 protein (amino acids E1023-T1327) is purified from SF9 cells. The assay is conducted using 0.11 μM of Tankyrase-1 protein and 3 μM nicotinamide adenine dinucleotide (NAD+, 2.12 μM 3H-NAD+ with a specific radioactivity of 1690 Ci/mol, 0.88 μM biotin- NAD+), in pH 7.5 Tris buffer (60 mM Tris, 1 mM DTT, 0.01% (v/v) Tween-20®, 2.5 mM MgCl2, 0.3 mg/mL BSA). For IC50 determination, 10 mM DMSO stock solution of a compound (MN-64) is sequentially diluted by two-fold in DMSO, and aliquots of the diluted solutions are transferred to 384-well assay plates and mixed with Tankyrase-1 solution[1]. |
| References: |
[1]. Narwal M, et al. Discovery of tankyrase inhibiting flavones with increased potency and isoenzyme selectivity. J Med Chem. 2013 Oct 24;56(20):7880-9. |
