Teplinovivint is a Potent Wnt/β-Catenin Signaling Pathway Inhibitor

The Wnt signaling pathway is a group of signal transduction pathways. They start from the proteins that transmit signals to cells through cell surface receptors. Specifically, the Wnt family secretes glycolipoproteins through transcriptional coactivators β-Catenin signals embryonic development and adult homeostasis. Signal transduction of the Wnt family is one of the basic mechanisms guiding cell proliferation, cell polarity, and cell fate during embryonic development and tissue homeostasis. Besides, the Wnt pathway mediates biological processes through classical or nonclassical pathways, which depends on the role of the cell cycle β-catenin in signal transduction. β-Catenin is the core component of the cadherin complex. Its stability is important for the activation of Wnt/ β-Catenin signaling is crucial. Furthermore, β-Catenin acts as the central hub of Wnt signaling through key protein-protein interactions with negative and positive effectors of the pathway.

Meanwhile, Wnt/β-Catenin signaling regulates key cell functions, including proliferation, differentiation, migration, genetic stability, apoptosis and stem cell renewal. In fact, APC in stem cells is absent or absent β-Catenin activation is essential for the formation of intestinal tumors. Therefore, it is necessary to block the drugs used in cancer treatment β-Catenin signaling has aroused great interest. Here, we will introduce a potent wnt/β-catenin signaling pathway inhibitor, Teplinovivint.

Teplinovivint is a Potent Wnt/β-Catenin Signaling Pathway Inhibitor.

To begin with, Teplinovivint is a potent wnt/β-catenin signaling pathway inhibitor. Nonetheless, Teplinovivint has anti-inflammatory activity and has the potential for tendinopathy research.

Next in importance, Teplinovivint with 0.0003-10 μM inhibits Wnt/p-catenin activity in human colorectal cancecell line (SW480) in a dose-dependent manner (EC50=152.9 nM). Interestingly, Teplinovivint inhibits SW480 cells (EC50=25 nM) and primary human mesenchymal stem cells (hMSCs; EC50=10.377 μM). Importantly, Teplinovivint induced the expression of SCXA, TenacinC and Tenomodulin, in a dose-dependent manner with an EC50 between 139-189 nM.

Once again, Teplinovivint with 10 mg/ml/day for 21 days via topical application causes amelioration of inflammation as well as tendon degeneration. Particularly, Teplinovivint results in a decrease of an inflammatory plasma biomarker, KC/GRO in the Collagenase-induced Tendon Injury Model. Obviously, Teplinovivint (1 mg/ml with 1% BA) has a Tmax of 1 hour in plasma.

All in all, Teplinovivint is a potent wnt/β-catenin signaling pathway inhibitor.


Vishal DESHMUKH, et al. Methods of using indazole-3-carboxamides and their use as wnt/b-catenin signaling pathway inhibitors. WO2018075858A1.