Rapamycin is a macrolide compound obtained from streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production.
Rapamycin is a member of the macrolide immunosuppressant family and a FRAP inhibitor. Rapamycin exhibits binding and inhibitory actions to the FK506 binding protein (FKBP5) proline rotamase via simultaneous binding by FKBP12 and FRAP. FRAP (RAFT1) proteins exhibit homology to PI 4- and PI 3-kinases, which have PI 4-kinase and autophosphorylating activities.The rapamycin/FKBP complex does not inhibit the FRAP PI 4-kinase activity, but does inhibit FRAP autophosphorylation. Rapamycin is unique in its ability to inhibit lymphokine induced cell proliferation at the G1 and S phase as well as an irreversible cellular arrest at the G1 phase in S. cerevisiae cells. It also exhibits selective signal blocking leading to the activation of p70/85 S6 kinase, which is potentially due to the inhibition of FRAP autophosphorylation or protein kinase activity. Angiogenesis inhibition is also exhibited,possibly through the inhibition of the Akt pathway. Rapamycin is an inhibitor of mTOR.
It is used to coat coronary stents, prevent organ transplant rejection and to treat a rare lung disease called lymphangioleiomyomatosis. It has immunosuppressant functions in humans and is especially useful in preventing the rejection of kidney transplants. It inhibits activation of T cells and B cells by reducing the production of interleukin-2 (IL-2).
Rapamycin is a triene macrolide antibiotic, which demonstrates anti-fungal, anti-inflammatory, anti-tumor and immunosuppressive properties. Rapamycin has been shown to block T-cell activation and proliferation, as well as, the activation of p70 S6 kinase and exhibits strong binding to FK-506 binding proteins. Rapamycin also inhibits the activity of the protein, mTOR, (mammalian target of rapamycin) which functions in a signaling pathway to promote tumor growth. Rapamycin binds to a receptor protein (FKBP12) and the rapamycin/FKB12 complex then binds to mTOR and prevents interaction of mTOR with target proteins in this signaling pathway.
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