Data from The Small Molecule IMR-1 Inhibits the Notch Transcriptional Activation Complex to Suppress Tumorigenesis

• DOI: 10.1158/0008-5472.c.6508100.v1
• Publication Date: 2023-03-31T22:41:11Z
• Authors: Luisana Astudillo; Thiago G. Da Silva; Zhiqiang Wang; Xiaoqing Han; Ke Jin; Jeffrey VanWye; Xiaoxia Zhu; Kelly Weaver; Taiji Oashi; Pedro E.M. Lopes; Darren Orton; Leif R. Neitzel; Ethan Lee; Ralf Landgraf; David J. Robbins; Alexander D. MacK...; Anthony J. Capobi...

<div>Abstract<p>In many cancers, aberrant Notch activity has been demonstrated to play a role in the initiation and maintenance of neoplastic phenotype cancer stem cells, which may allude its additional involvement metastasis resistance therapy. Therefore, is an exceedingly attractive therapeutic target cancer, but full range potential targets within pathway underexplored. To date, there are no small-molecule inhibitors that directly intracellular or assembly transcriptional activation complex. Here, we describe <i>in vitro</i> assay quantitatively measures complex on DNA. Integrating this approach with computer-aided drug design, explored ligand-binding sites screened for compounds could disrupt We identified inhibitor, termed Inhibitor Mastermind Recruitment-1 (IMR-1), disrupted recruitment Mastermind-like 1 chromatin, thereby attenuating gene transcription. Furthermore, IMR-1 inhibited growth Notch-dependent cell lines significantly abrogated patient-derived tumor xenografts. Taken together, our findings suggest novel class targeting represent new paradigm Notch-based anticancer therapeutics, warranting further preclinical characterization. <i>Cancer Res; 76(12); 3593–603. ©2016 AACR</i>.</p></div>