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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.
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