Sirolimus and Everolimus Pathway: Reviewing Candidate Genes Influencing Their Intracellular Effects.

摘要: Sirolimus (SRL) and everolimus (EVR) are mammalian targets of rapamycin inhibitors (mTOR-I) largely employed in renal transplantation oncology as immunosuppressive/antiproliferative agents. SRL was the first mTOR-I produced by bacterium Streptomyces hygroscopicus approved for several medical purposes. EVR, derived from SRL, contains a 2-hydroxy-ethyl chain 40th position that makes drug more hydrophilic than increases oral bioavailability. Their main mechanism action is inhibition mTOR complex 1 regulation factors involved crucial cellular functions including: protein synthesis, angiogenesis, lipid biosynthesis, mitochondrial biogenesis function, cell cycle, autophagy. Most proteins/enzymes belonging to aforementioned biological processes encoded numerous tightly regulated genes. However, at moment, polygenic influence on SRL/EVR effects still not completely defined, its comprehension represents key challenge researchers. Therefore, obtain complete picture network connected SRL/EVR, we decided review major evidences available literature regarding genetic biology/pharmacology build, time, useful specific “SRL/EVR genes-focused pathway”, possibly employable starting point future in-depth research projects.