雷帕鸣有抗肿瘤作用吗

(Sirolimus) 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. Sirolimus is a white crystal with a melting point of 183~184°C 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.

Rapamin (sirolimus) 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 sirolimus blocks signaling through different cytokine receptors and blocks the progression of T lymphocytes and other cells from the GI phase to the S phase. Compared with FK506, sirolimus 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 sirolimus inhibits the body's immune function by affecting unique cell signaling pathways.

Sirolimus and FK506 share the same receptor in the body, namely FK506 immunobinding protein (FKBP). After rapamycin (sirolimus) binds to FKBP, on the one hand, it inhibits the activation of 70-KSU6 kinase (p7), preventing the ribosome 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) that has a homologous sequence to phospholipid phthaloinositide kinase, that is, the combination product of the rapamycin (sirolimus) and FKBP complex with mTOR can block the immune response triggered by the activation of mTOR by H, -2, U, -15 or CD28/B7 costimulatory pathways, thereby exerting a powerful immunosuppressive effect.

Rapamin (sirolimus) was approved by the FDA on May 30, 2007 for the treatment of advanced renal disease. It has entered clinical phase 4 for the treatment of mantle cell lymphoma. Rapamycin (sirolimus) is an inhibitor of the rapamycin target protein mTOR. mTOR is a downstream protein of the PI3K/AKT pathway. This pathway is abnormally activated in a variety of tumor cells. It can control the growth of tumor cells by inhibiting the activity of mTOR and thereby inhibiting the activity of its downstream S6 ribosomal protein kinase (S6K1). In addition, (sirolimus) has its own activity and can be converted into rapamycin in the body to inhibit mTOR.