====== MPT0L145 ======

MPT0L145, a highly potent [[PIK3C3]] inhibitor

----

[[CDK4/6 inhibitor]]s are newly [[FDA]]-approved agents to treat [[HER2-positive breast cancer]], HER2-negative advanced, and metastatic [[breast cancer]]s, and preclinical results showed that CDK4/6 inhibitors significantly reduced cell proliferation and [[tumor growth]]. However, several studies have suggested that CDK4/6 inhibitor-induced non-genetic changes caused treatment failure, including [[autophagy]] activation. Therefore, Hsieh et al. aimed to combine an autophagy inhibitor, [[MPT0L145]], with [[abemaciclib]] to improve therapeutic efficiency. The use of abemaciclib effectively inhibited cell proliferation via suppression of RB phosphorylation and induced autophagy activation in [[glioblastoma]] cancer cells. MPT0L145 treatment alone not only blocked autophagy activation, but also induced generation of ROS and DNA damage in a concentration-dependent manner. Importantly, MPT0L145 had a comparable penetration ability to TMZ in our blood brain barrier permeability assay. Combined MPT0L145 with abemaciclib significantly reduced cell proliferation, suppressed RB phosphorylation, and increased ROS production. In conclusion, the data suggested that blocking autophagy by MPT0L145 synergistically sensitized Glioblastoma cancer cells to abemaciclib and represents a potential therapeutic strategy for treating Glioblastoma in the future
((Hsieh TH, Liang ML, Zheng JH, Lin YC, Yang YC, Vo TH, Liou JP, Yen Y, Chen
CH. Combining an Autophagy Inhibitor, [[MPT0L145]], with [[Abemaciclib]] Is a New
Therapeutic Strategy in Glioblastoma Treatment. Cancers (Basel). 2021 Dec 4;13(23):6117.
doi: 10.3390/cancers13236117. PMID: 34885226; PMCID: PMC8656550.)).