A Novel Anticancer Stem Cell Compound Derived from Pleuromutilin Induced Necroptosis of Melanoma Cells

  • J Med Chem. 2021 Nov 11;64(21):15825-15845. doi: 10.1021/acs.jmedchem.1c01123.
Kun Zhang  1 ,  Wei Song  1 ,  Mingming Wei  1 ,  Yue Sun  1 ,  Ning Wang  1 ,  Lan Ma  1 ,  Xuan Yu  2 ,  Ruolin Gao  1 ,  Ruonan Wang  1 ,  Yan Zhang  1 ,  Nan Zheng  1 ,  Ning Li  1 ,  Linrong Mu  1 ,  Zhiwen Tang  1 ,  Xuechun Li  1 ,  Cheng Yang  1 ,  Guang Yang  1
Affiliations
  • 1. State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300071, P. R. China.
  • 2. Tianjin Institute for Drug Control, Tianjin 300021, P. R. China.
PMID: 34704758 DOI: 10.1021/acs.jmedchem.1c01123
Abstract

Necroptosis has been recently confirmed as a non-apoptotic form of programmed cell death. Discovery of novel chemical entities, capable of inducing Necroptosis of Cancer cells, is likely to act as an alternative strategy for dealing with drug resistance clinically. In this study, the identification of a novel Pleuromutilin derivative (compound 38) is presented, capable of significantly increasing the cellular level of ROS and inducing melanoma Cancer cell death via Necroptosis. Furthermore, compound 38 noticeably ablated various Cancer Stem Cells and inhibited the growth of melanoma Cancer cells both in vitro and in vivo. Moreover, 38 exhibited low toxicity in animal models and excellent PK properties, which is currently being verified as a potential Anticancer drug candidate.

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