| Chemical Properties | Back Directory | [Boiling point ]
444.1±45.0 °C(Predicted) | [density ]
1.20±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO: 56 mg/mL (198.34 mM);Ethanol: 6 mg/mL (21.25 mM) | [form ]
Solid | [pka]
10.92±0.40(Predicted) | [color ]
Off-white to light yellow | [Water Solubility ]
Water: Insoluble |
| Hazard Information | Back Directory | [Uses]
MSC2504877 (M2912) is a potent and orally active tankyrase inhibitor with IC50s of 0.0007, 0.0008, 0.54 μM for TNKS, TNKS2, PARP1, respectively. MSC2504877 increases the expression of AXIN2 and TNKS protein levels and decreases β-catenin levels. MSC2504877 shows anti-tumor activity[1]. | [Biological Activity]
M2912 (MSC2504877) is a very potent TNKS1/TNKS2 inhibitor (IC50=0.6 nM for TNKS1) with exquisite selectivity over other PARP family enzymes and favorable compound properties. This inhibitor potently modulates the Wnt/β-catenin pathway by elevating the levels of axin2 (EC50=17 nM) and tankyrase in DLD1 cells in a dose-dependent manner resulting in reduced cellular Wnt reporter activity. | [in vivo]
MSC2504877 (30 mg/kg; p.o.; once) inhibits TNKS and Wnt signalling in mice[1].
MSC2504877 (30 mg/kg+?palbociclib (HY-50767) 150?mg/kg; p.o.; once) suppresses hyperproliferation in Apc defective cells in vivo[1]. | Animal Model: | CB17 SCID mice (APC mutant COLO320DM tumour cell xenografts)[1] | | Dosage: | 30 mg/kg | | Administration: | P.o.; once | | Result: | Elicited an increase in both TNKS and AXIN2 levels in tumours, peaking at 6–10?hours after drug administration and falling 18?hours after. |
| Animal Model: | Villin-CreERT2; Apcfl/fl mice[1] | | Dosage: | 50 mg/kg +?palbociclib (150?mg/kg) | | Administration: | P.o.; once | | Result: | Suppressed the expression of the archetypal Wnt target gene and stem cell marker Lgr5 and combination drug treatment caused a profound increase in nuclear p21. |
| [IC 50]
PARP1: 0.54 μM (IC50); TNKS: 0.0007 μM (IC50); TNKS2: 0.0008 μM (IC50) | [References]
[1] Buchstaller HP, et al. J Med Chem. 2021 Jul 22;64(14):10371-10392. |
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