Jeitany, Maya published the artcileNovel carfilzomib-based combinations as potential therapeutic strategies for liposarcomas, Computed Properties of 218136-59-5, the publication is Cellular and Molecular Life Sciences (2021), 78(4), 1837-1851, database is CAplus and MEDLINE.
Proteasome inhibitors, such as bortezomib and carfilzomib, have shown efficacy in anti-cancer therapy in hematol. diseases but not in solid cancers. Here, we found that liposarcomas (LPS) are susceptible to proteasome inhibition, and identified drugs that synergize with carfilzomib, such as selinexor, an inhibitor of XPO1-mediated nuclear export. Through quant. nuclear protein profiling and phospho-kinase arrays, we identified potential mode of actions of this combination, including interference with ribosome biogenesis and inhibition of pro-survival kinase PRAS40. Furthermore, by assessing global protein levels changes, FADS2, a key enzyme regulating fatty acids synthesis, was found down-regulated after proteasome inhibition. Interestingly, SC26196, an inhibitor of FADS2, synergized with carfilzomib. Finally, to identify further combinational options, we performed high-throughput drug screening and uncovered novel drug interactions with carfilzomib. For instance, cyclosporin A a known immunosuppressive agent enhanced carfilzomibs efficacy in vitro and in vivo. Altogether, these results demonstrate that carfilzomib and its combinations could be repurposed for LPS clin. management.
Cellular and Molecular Life Sciences published new progress about 218136-59-5. 218136-59-5 belongs to piperazines, auxiliary class Metabolic Enzyme,D6D, name is 2,2-Diphenyl-5-(4-((pyridin-3-ylmethylene)amino)piperazin-1-yl)pentanenitrile, and the molecular formula is C27H29N5, Computed Properties of 218136-59-5.
Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics