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

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.