期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 297, 期 1, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.jbc.2021.100903
关键词
-
资金
- University Grants Commission, India
- Ministry of Human Resource Development, India
- Department of Science and Technology, India [BT/11/IYBA/2018/06]
- Science and Engineering Research Board Grant, India [SB/S2/RJN-072/2015, ECR/2017/00092]
- Institute of Eminence Scheme, BHU
c-Myc is a vital transcription factor that regulates gene expression and forms a heterodimer with MAX. L755507, a newly discovered small molecule, inhibits the formation of the c-Myc-MAX heterodimer and shows potential as an anti-tumor agent.
c-Myc is a transcription factor that plays a crucial role in cellular homeostasis, and its deregulation is associated with highly aggressive and chemotherapy-resistant cancers. After binding with partner MAX, the c-Myc-MAX heterodimer regulates the expression of several genes, leading to an oncogenic phenotype. Although considered a crucial therapeutic target, no clinically approved c-Myc-targeted therapy has yet been discovered. Here, we report the discovery via computer-aided drug discovery of a small molecule, L755507, which functions as a c-Myc inhibitor to efficiently restrict the growth of diverse Myc-expressing cells with low micromolar IC50 values. L755507 successfully disrupts the c-Myc-MAX heterodimer, resulting in decreased expression of c-Myc target genes. Spectroscopic and computational experiments demonstrated that L755507 binds to the c-Myc peptide and thereby stabilizes the helix-loop-helix conformation of the c-Myc transcription factor. Taken together, this study suggests that L755507 effectively inhibits the c-Myc-MAX heterodimerization and may be used for further optimization to develop a cMyc-targeted antineoplastic drug.
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