Sirolimus analogs

The initial success with sirolimus has led to the search of sirolimus analogs, Among these are everolimus (a new macrocylic triene derivative), ABT 578, and other antiimmunosuppressive compounds such as mycophenolic acid, cyclosporine, and tacrolimus, which inhibit proliferation via GI arrest and reduce the immune response. Data from animal experiments suggest that oral everolimus administered for one month effectively inhibits NIH (37) however, human trials have not been conducted. 

Systemic immunosuppressive therapies in the treatment of restenosis sirolimus and sirolimus analogs in experimental and clinical data... 

More recently, with sirolimus analogs such as everolimus or with the use of nanoparticles of paclitaxel, a significant... 

More recently, studies of sirolimus in a vascular allograft rejection model in nonhuman primates by Ikonen et al. (95), a severe immune-mediated vascular disorder, have shown lesion inhibition and possibly regression. Finally, clinical studies by Mancini et al. (96) and Eisen et al. (97) with a sirolimus analog on vasculopathy and also by Keogh et al. (98) on coronary... 

Everolimus (40 Afinitor Novartis, 2009), a rapamycin analog, is the 42-0-(2-hydroxyethyl) derivative of sirolimus (34), and is marketed as an immunosuppressant by Novartis under the tradename Afinitor for use in advanced renal cell carcinoma.In March 2009, the FDA approved everolimus (40) for use against advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib. The drug works similarly to sirolimus as an inhibitor of mTOR (mammalian target of rapamycin), a serine-threonine kinase, downstream of the PI3K/AKT pathway. Everolimus (40) binds to an intracellular protein, EKBP-12, resulting in an inhibitory... 

Indications Renal cell carcinoma, other cancers Category Analog of sirolimus mTOR inhibitor Half-life I 3-25 Hours... 

The second class of mTOR inhibitors is comprised of small molecules that directly interact at the ATP-binding site of mTOR. In contrast to rapamycin and its analogs, these compounds inhibit both functional complexes of mTOR, mTORCl and mTORC2. The dual inhibition of both complexes may have potential clinical benefits, as inhibition solely of mTORCl has been correlated with a negative feedback mechanism,120 and there is evidence that certain mTORCl functions are not fully inhibited by sirolimus.121 Relative to the rapalogs, the members of this second class of mTOR compounds are a newer entry to the field and have only recently begun clinical trials. 

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