Journal ArticleDOI
Small-Molecule Inhibitors Targeting the Canonical WNT Signaling Pathway for the Treatment of Cancer.
TLDR
In this paper, the authors summarize recent progress in the discovery and development of small-molecule inhibitors targeting the canonical WNT pathway, focusing on their specific target proteins, in vitro and in vivo activities, physicochemical properties, and therapeutic potential.Abstract:
Canonical WNT signaling is an important developmental pathway that has attracted increased attention for anticancer drug discovery From the production and secretion of WNT ligands, their binding to membrane receptors, and the β-catenin destruction complex to the expansive β-catenin transcriptional complex, multiple components have been investigated as drug targets to modulate WNT signaling Significant progress in developing WNT inhibitors such as porcupine inhibitors, tankyrase inhibitors, β-catenin/coactivators, protein-protein interaction inhibitors, casein kinase modulators, DVL inhibitors, and dCTPP1 inhibitors has been made, with several candidates (eg, LGK-974, PRI-724, and ETC-159) in human clinical trials Herein we summarize recent progress in the drug discovery and development of small-molecule inhibitors targeting the canonical WNT pathway, focusing on their specific target proteins, in vitro and in vivo activities, physicochemical properties, and therapeutic potential The relevant opportunities and challenges toward maintaining the balance between efficacy and toxicity in effectively targeting this pathway are also highlightedread more
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Journal ArticleDOI
Discovery of an Orally Bioavailable Small-Molecule Inhibitor for the β-Catenin/B-Cell Lymphoma 9 Protein-Protein Interaction
Zhen Wang,Min Zhang,Victor Quereda,Sylvia M Frydman,Qianqian Ming,Vincent C. Luca,Derek R. Duckett,Haitao Ji +7 more
TL;DR: In this paper, a drug-like small molecule, ZW4864, was reported to selectively disrupt the protein-protein interaction (PPI) between B-cell lymphoma 9 (BCL9) and β-catenin, while sparing the β-Catenin/E-cadherin PPI.
Journal ArticleDOI
Discovery of 1-Benzoyl 4-Phenoxypiperidines as Small-Molecule Inhibitors of the β-Catenin/B-Cell Lymphoma 9 Protein-Protein Interaction.
TL;DR: In this paper, structure-based design and optimization were performed to develop small-molecule β-catenin/B-cell lymphoma 9 (BCL9) inhibitors and improve their inhibitory activities.
Journal ArticleDOI
Biophysical Survey of Small-Molecule β-Catenin Inhibitors: A Cautionary Tale
Michael A McCoy,Dominique Spicer,Neil J. Wells,Kurt Hoogewijs,Marc Fiedler,Matthias G. J. Baud +5 more
TL;DR: This study provides an account of the claimed (and some putative) small-molecule ligands of β-catenin from the literature and shows that most of these molecules contain promiscuous chemical substructures notorious for interfering with screening assays.
Journal ArticleDOI
A chemical perspective on the modulation of TEAD transcriptional activities: Recent progress, challenges, and opportunities.
Jia-yan Lou,Yuhang Lu,Jing-Jy Cheng,Feilong Zhou,Ziqin Yan,Daizhou Zhang,Xiangjing Meng,Yujun Zhao +7 more
TL;DR: A review of TEAD inhibitors and activators can be found in this paper , where a large number of inhibitors have been reported with decent in vitro potencies, a few exerted robust and compelling in vivo efficacies, and three that are undergoing clinical trials for the treatment of human cancers.
Journal ArticleDOI
Immunogenomic classification of hepatocellular carcinoma patients for immune check-point inhibitors therapy: cui bono?
Ruben Hernaez,Matías A. Avila +1 more
TL;DR: Notably, 50%–60% of patients with HCC will receive systemic therapies, 1 including immune check- point inhibitors (ICIs).
References
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