Seco Rapamycin

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)