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Ref Type Journal Article
PMID (28500231)
Authors Maheshwari S, Avula SR, Singh A, Singh LR, Palnati GR, Arya RK, Cheruvu SH, Shahi S, Sharma T, Meena S, Singh AK, Kant R, Riyazuddin M, Bora HK, Siddiqi MI, Gayen JR, Sashidhara KV, Datta D
Title Discovery of a Novel Small-Molecule Inhibitor that Targets PP2A-β-Catenin Signaling and Restricts Tumor Growth and Metastasis.
Journal Vol Issue Date Pages Journal Short Title
Molecular cancer therapeutics 16 9 2017 Sep 1791-1805 Mol Cancer Ther
URL
Abstract Text Molecular hybridization of different pharmacophores to tackle both tumor growth and metastasis by a single molecular entity can be very effective and unique if the hybrid product shows drug-like properties. Here, we report synthesis and discovery of a novel small-molecule inhibitor of PP2A-β-catenin signaling that limits both in vivo tumor growth and metastasis. Our molecular hybridization approach resulted in cancer cell selectivity and improved drug-like properties of the molecule. Inhibiting PP2A and β-catenin interaction by selectively engaging PR55α-binding site, our most potent small-molecule inhibitor diminished the expression of active β-catenin and its target proteins c-Myc and Cyclin D1. Furthermore, it promotes robust E-cadherin upregulation on the cell surface and increases β-catenin-E-Cadherin association, which may prevent dissemination of metastatic cells. Altogether, we report synthesis and mechanistic insight of a novel drug-like molecule to differentially target β-catenin functionality via interacting with a particular subunit of PP2A. Mol Cancer Ther; 16(9); 1791-805. ©2017 AACR.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
CS-11 CS-11 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
CS-11 CS-11 binds to PR55-alpha, the regulatory subunit of PP2A, resulting in decreased nuclear beta-catenin activity and reduced expression of downstream targets and increased cell surface levels of E-cadherin and activated beta-catenin, which may lead to increased tumor cell apoptosis and decreased metastasis (PMID: 28500231).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References