期刊
CELL CHEMICAL BIOLOGY
卷 26, 期 5, 页码 711-+出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2019.02.009
关键词
-
资金
- National Cancer Institute [R01-CA160860, P30-CA14051, U01-CA176152]
- NIH/NCI [CA170378PQ2, 1U01CA188383-01/S1]
- Leukemia & Lymphoma Society
- Ono Pharma Foundation
- MIT Deshpande Center for Technological Innovation
- MIT Center for Precision Cancer Medicine
- AACR-Bayer Innovation and Discovery Grant
- Merkin Institute Fellows Program at the Broad Institute
- Cancer Prevention Research Institute of Texas [RR150093]
- NIH
- NCI [1R01CA215452-01]
- GSK-MIT Gertrude B. Elion Research Fellowship Program for Drug Discovery and Disease
- Ludwig Center Fund at MIT
- Koch Institute Graduate Fellowship in Cancer Research
- Lymphoma Research Foundation Postdoctoral Fellowship
- Koch Institute Quinquennial Cancer Research Fellowship
- Ludwig Center for Molecular Oncology Graduate Fellowship
The transcription factor Max is a basic-helix-loop-helix leucine zipper (bHLHLZ) protein that forms homodimers or interacts with other bHLHLZ proteins, including Myc and Mxd proteins. Among this dynamic network of interactions, the Myc/Max heterodimer has crucial roles in regulating normal cellular processes, but its transcriptional activity is deregulated in a majority of human cancers. Despite this significance, the arsenal of high-quality chemical probes to interrogate these proteins remains limited. We used small molecule microarrays to identify compounds that bind Max in a mechanistically unbiased manner. We discovered the asymmetric polycyclic lactam, KI-MS2-008, which stabilizes the Max homodimer while reducing Myc protein and Myc-regulated transcript levels. KI-MS2-008 also decreases viable cancer cell growth in a Myc-dependent manner and suppresses tumor growth in vivo. This approach demonstrates the feasibility of modulating Max with small molecules and supports altering Max dimerization as an alternative approach to targeting Myc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据