Latest research on RAD001

Everolimus is a derivative of Rapamycin (sirolimus), and works similarly to Rapamycin as an mTOR (mammalian target of rapamycin) inhibitor. It is currently used as an immunosuppressant to prevent rejection of organ transplants. In a similar fashion to other mTOR inhibitors Everolimus' effect is solely on the mTORC1 protein and not on the mTORC2 protein.

RAD001 side effects

Furthermore, high levels of phosphorylated AKT, GSK3β, and TSC2 have also been demonstrated to correlate with increased sensitivity to RAD001 (everolimus).149 [source, 2016]
Our data demonstrate that TGFbeta 2 increase in R527H cells is associated with activation of the Akt/mTOR pathway and this effect is reversed by TGFbeta 2 neutralizing antibody, statins and the mTOR inhibitor RAD001, which also avoid the aberrant osteoclastogenesis triggered by laminopathic culture media. [source, 2015]
RAD001 minimally affected Akt activity, but elicited protein increase (Figure 4A), possibly due to a feedback mechanism. [source, 2015]
However, the combination of HCQ and RAD001 together did not exhibit statistically increased growth inhibition compared to either drug alone. [source, 2015]
Consistent with the literature, RAD001 treatment caused complete inhibition of S6 phosphorylation on both pairs of residues, inhibited phosphorylation of ser371 of P70S6K, and inhibited 4EBP1 phosphorylation in all three cell lines (Fig 3B). [source, 2015]
However, HCQ or combination with RAD001 treatment to Atg7-depleted cells enhanced apoptosis shown as increased cleaved PARP level and inhibited cell proliferation (Fig 4B). [source, 2015]
We found that bortezomib treatment had no effect on the levels of phospho-S6 in untreated and RAD001 treated cells, but resulted in a large increase in phospho-S6 levels in HCQ treated cells (Fig 6). [source, 2015]
Other chemotherapeutics, routinely used in clinic, may also have anti-angiogenic activity in vitro or in vivo [96] as: (1) Paclitaxel [97], Doxorubicin and Thalidomide [98] which seems to be mediated via inhibition of VEGF and bFGF [99]; (2) Celecoxib, which may cause a time-dependent reduction in circulating angiogenic markers; (3) bisphosphonates may have anti-angiogenic effects [100] via reduction of VEGF and PDGF serum levels [101]; (4) PI3K inhibitors (including Rapamycin analogues as temsirolimus (CCI-779) and everolimus (RAD001)) decrease tumor angiogenesis [102], [103], [104] via the inhibition of HIF-1alpha caused by the blockade of mTOR activity. [source, 2015]
Reversely, Madlaina et al found that increased AKT Ser473 phosphorylation induced by RAD001 (everolimus), an mTORC1 (mTOR/Raptor) inhibitor, was Rictor dependent[38]. [source, 2015]
CBY1 release from 14-3-3σ in response to RAD001 was associated with a significant increase of CBY1 levels in the cytoplasm (p<0.01), but not in the nucleus (p<0.1) (Fig 3B). [source, 2015]