M2912
(Synonyms: MSC2504877) 目录号 : GC25603M2912 (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.
Cas No.:1460286-21-8
Sample solution is provided at 25 µL, 10mM.
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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.
[1] Buchstaller HP, et al. J Med Chem. 2021 Jul 22;64(14):10371-10392.
Cas No. | 1460286-21-8 | SDF | Download SDF |
别名 | MSC2504877 | ||
分子式 | C17H18N2O2 | 分子量 | 282.34 |
溶解度 | DMSO: 56 mg/mL (198.34 mM);Water: Insoluble;Ethanol: 6 mg/mL (21.25 mM) | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg | |
1 mM | 3.5418 mL | 17.7091 mL | 35.4183 mL |
5 mM | 0.7084 mL | 3.5418 mL | 7.0837 mL |
10 mM | 0.3542 mL | 1.7709 mL | 3.5418 mL |
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% DMSO % % Tween 80 % saline | ||||||||||
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2.
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Optimization of a Screening Hit toward M2912, an Oral Tankyrase Inhibitor with Antitumor Activity in Colorectal Cancer Models
J Med Chem 2021 Jul 22;64(14):10371-10392.PMID:34255518DOI:10.1021/acs.jmedchem.1c00800.
Constitutive activation of the canonical Wnt signaling pathway, in most cases driven by inactivation of the tumor suppressor APC, is a hallmark of colorectal cancer. Tankyrases are druggable key regulators in these malignancies and are considered as attractive targets for therapeutic interventions, although no inhibitor has been progressed to clinical development yet. We continued our efforts to develop tankyrase inhibitors targeting the nicotinamide pocket with suitable drug-like properties for investigating effects of Wnt pathway inhibition on tumor growth. Herein, the identification of a screening hit series and its optimization through scaffold hopping and SAR exploration is described. The systematic assessment delivered M2912, a compound with an optimal balance between excellent TNKS potency, exquisite PARP selectivity, and a predicted human PK compatible with once daily oral dosing. Modulation of cellular Wnt pathway activity and significant tumor growth inhibition was demonstrated with this compound in colorectal xenograft models in vivo.