Latest research on Rapamycin

A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to immunophilins. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. [PubChem]

Latest findings

We present compelling evidence that the likely cause of XLID in this family is a missense mutation in ARHGEF9, encoding a neuronal RhoGEF known as collybistin (CB) involved in both inhibitory synaptic organization and mammalian target of Rapamycin complex 1 (mTORC1) signaling pathways (Machado et al., 2015). [source, 2016]
The HK-2 cells were seeded in 96-well plates at 1×104 cells/well and used to evaluate cell viability following treatment with ioxitalamate (Telebrix™; Guerbet, Paris, France) and/or resveratrol (Tocris Bioscience, Minneapolis, MN, USA), NAC (Sigma-Aldrich, St. Louis, MO, USA), necrostatin-1 (Nec-1) (BioVision, Inc., Milpitas, CA, USA), Sirolimus and everolimus (both from LC Laboratories, Woburn, MA, USA), and EX-527 and SRT-1720 (both from Selleck Chemicals, Houston, TX, USA). [source, 2016]
In some experiments (the cytotoxicity of ioxitalamate plus the autophagy inducers, Sirolimus or everolimus, as well as the cytotoxicity of ioxitalamate plus the SIRT1 inhibitor, EX-527, or the SIRT1 activator, SRT-1720), ioxitalamate was considered as the control in order to elucidate the mechanisms involved. [source, 2016]
To confirm that this phenomenon was a compensatory result or autophagic death, the cells were treated with the autophagy inducers, sirolimus and everolimus, so-called mammalian target of Rapamycin (mTOR) inhibitors, in addition to ioxitalamate for 48 h. [source, 2016]
Both Sirolimus and everolimus (both at 1 μM) significantly aggravated ioxitala-mate-induced cytotoxicity (p=0.008 and 0.01, respectively; n=3 experiments) (Fig. 2G). [source, 2016]
In this study, ioxitalamate-induced autophagy played a pro-apoptotic role, as the autopahy inducers, Sirolimus and everolimus, potentiated ioxitalamate-induced cytotoxicity. [source, 2016]
By contrast, Sirolimus has been shown to alleviate Cisplatin induced nephropathy (42). [source, 2016]
Sirolimus and everolimus bind to FKBP12 and inhibit mTOR, a key regulator of cell proliferation, growth, apoptosis and survival in response to growth factors and cytokines (43). [source, 2016]
For example, Sirolimus has been shown to inhibit the growth factor-induced proliferation of renal proximal tubule cells and promote apoptosis by blocking the survival effects of the same growth factors mediated by the inhibition of p70S6k (44). [source, 2016]
Figure 3A shows an example of cell line-specific expression in 24 cancer types from CCLE for mTOR (encoding mammalian target of Rapamycin) which is a critically deregulated gene in the cell-signaling pathway in various human cancer types (55). [source, 2016]