Small rapamycin activity

Figure 5.5 Small-molecule enhancers of rapamycin activity (SMER) detected in this study.

Small molecule antagonists such as CsA, FK506, and rapamycin all inhibit IL-5 production (464,465). Glucocorticoids, in addition to decreasing bronchial hyperresponsiveness, can also downregulate IL-5 production (466-468). OM-01 suppresses IL-5 protein production, mRNA expression, and transcriptional activity in PBMCs with no effect on either IL-2 or IL-4 (469,470). (The structure for OM-01 has not been disclosed.)... 

Phillips R. J., Mestas J., Gharaee-Kermani M., et al. (2005) Epidermal growth factor and hypoxia-induced expression of CXC chemokine receptor 4 on non-small cell lung cancer cells is regulated by the phosphatidylinositol 3-kinase/PTEN/AKT/mammalian target of rapamycin signaling pathway and activation of hypoxia inducible factor-lalpha. J Biol Chem., 280, 22473-81. 

Shortly after the discovery of calcineurin as the mechanistic key for FK506 and CsA action, the mechanism of action of rapamycin began to unfold. It had already been noted that rapamycin blocked the IL-2 stimulated G1 to S phase transition in T-cells, inhibiting cell division. Treatment of T-cells with rapamycin was found to result in decreased enzymatic activity of several kinases, including p70 S6 kinase (a 70 kDa protein which phosphorylates the S6 protein of the small ribosomal subunit),27-29 and cyclin-dependent kinases of 33 and 34 kDa.30,31 However, in vitro experiments demonstrated that these kinases were not directly inhibited by the FKBP-rapamycin complex. In 1993, two yeast proteins were identified that appeared to be involved in the mechanistic pathway and mutations in these proteins conferred resistance to rapamycin-induced cytotoxicity.32 These proteins were named TORI and TOR2 (targets of rapamycin). 

Yu J, Henske EP. Estrogen-induced activation of mammalian target of rapamycin is mediated via tuberin and the small GTPase ras homologue enriched in brain. Cancer Res 2006 66(19) 9461-9466. 

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