Rapamune治疗效果怎么样？

Rapamin () is a lipophilic nitrogen-containing 36$ macrolide antibiotic naturally produced from Streptomyees hygroscopicus. Its molecular formula is C51H79NO13 and its molecular weight is 914.17. Rapamune is a white crystal with a melting point of 183~184℃ and an optical rotation of -147°~-157° (c=l.02, chloroform). Soluble in methanol, ethanol, acetone, ethyl acetate, chloroform or ether, insoluble in hexane or petroleum ether, insoluble in water.  

Rapamune and FK506 are structural homologs. Although they act on the same receptor, their immune action mechanisms are different. FK506 inhibits the proliferation of T lymphocytes from the G0 phase to the G1 phase, while Rapamune blocks signaling through different cytokine receptors, blocking the progression of T lymphocytes and other cells from the GI phase to the S phase. Compared with FK506, Rapamune can block the calcium-dependent and calcium-independent signaling pathways P1 of T lymphocytes and B lymphocytes. Current research shows that FK506 and cyclosporin A produce immunosuppressive effects by inhibiting calcineurin, while Rapamune inhibits the body's immune function by affecting unique cell signaling pathways. Rapamune and FK506 share the same receptor in the body, namely FK506 immunobinding protein (FKBP). After Rapamune binds to FKBP, on the one hand, it inhibits the activation of 70-KSU6 kinase (p7), preventing the ribosomal 40S subunit S6 protein from phosphorylating g7, affecting protein synthesis; on the other hand, it inhibits Cyclin D2, D3 The expression of cell cycle-dependent kinases, namely cdk4 and cdk6, and the activation of Cyclin E-cdk2 complex make cells stagnant in the middle and late stages of GI and unable to continue to proliferate. Its direct target may be a protein mammalian'rOR (mTOR) with a homologous sequence to phospholipid phthalinositide kinase, that is, the combination product of rapamycin () and FKBP complex with mTOR can block the immune response triggered by mTOR activation by H, -2, U, -15 or CD28/B7 costimulatory pathways, thus exerting a powerful immunosuppressive effect.