Rapamycin is a natural macrolide immunosuppressant that activates mTORC1. Seco rapamycin (sodium salt) is a nonenzyme-dependent degradation product of rapamycin resulting from ester hydration followed by dehydration.1 It has less than 4% of the potency of rapamycin in a thymocyte proliferation assay.1 Rapamycin quickly degrades to two ring-opened products, including seco rapamycin, in the cytoplasm or in homogenates of Caco-2 cells.2 Like rapamycin, seco rapamycin is secreted from cells by P-glycoprotein and metabolized to a common dihydro species.3 While seco rapamycin poorly activates mTOR, it mimics rapamycin in its ability to inhibit the proteasome.4
1.Wang, C.P., Chan, K.W., Schiksnis, R.A., et al.High performance liquid chromatographic isolation, spectroscopic characterization, and immunosuppressive activities of two rapamycin degradation productsJ. Liq. Chromatogr.17(16)3383-3392(1994) 2.Paine, M.F., Leung, L.Y., Lim, H.K., et al.Identification of a novel route of extraction of sirolimus in human small intestine: Roles of metabolism and secretionJ. Pharmacol. Exp. Ther.301(1)174-186(2002) 3.Paine, M.F., Leung, L.Y., and Watkins, P.B.New insights into drug absorption: Studies with sirolimusTher. Drug Monit.26(5)463-467(2004) 4.Osmulski, P.A., and Gaczynska, M.Rapamycin allosterically inhibits the proteasomeMol. Pharmacol.84(1)104-113(2013)