Possible Interaction: Caffeine and Sirolimus

“ Rapamycin and FK506 increase the sensitivity of RyRs to agonists such as caffeine and could be a cause of cardiac dysfunction associated with high-dose immunosuppressant therapy by promoting leakage of Ca2+ from the sarcoplasmic reticulum.”

“Our results show that two deletion strains are thermosensitive whereas two strains are sensitive to caffeine , an inhibitor of the target of rapamycin pathway.”

“In addition, caffeine suppressed the phosphorylation of insulin-stimulated IRS-1 Ser(636/639) and upstream kinases, including the mammalian target of rapamycin and p70S6 kinase.”

“Under these conditions FK506, which displaces FKBP12 (to inhibit calcineurin) and rapamycin , which displaces FKBP12 (to inhibit mTOR), each increased the [Ca(2+)](c) rise evoked by caffeine.”

“In vitro, caffeine promoted autophagy by suppressing the mechanistic target of rapamycin (mTOR) pathway and inhibited activation of the NLRP3 inflammasome.”

“In single-cell eukaryotes, however, caffeine somehow impairs cellular fitness by compromising cell wall integrity, inhibiting target of rapamycin (TOR) signaling and growth, and overriding cell cycle arrest caused by DNA damage.”

“Here we exploited the combinatorial action of rapamycin and caffeine , which inhibit fission yeast growth in a TORC1-dependent manner.”

“Moreover, treatment of S. pombe cells with rapamycin plus caffeine induces starvation‐specific gene expression and autophagy, similarly to cells with reduced TORC1 activity.”