Seco Rapamycin, also known as Secorapamycin A, is a ring-opened derivative derived from Rapamycin. It has been observed that Seco-rapamycin does not impact the function of mTOR.

The study investigated the metabolism of Seco Rapamycin (D2) to dihydro Sirolimus (M2) in human tissue homogenates, including liver, jejunal mucosal, and Caco-2, as well as in Caco-2 cell monolayers. Using 20μM of Seco Rapamycin, it was determined that all tested homogenates could convert Seco Rapamycin to M2 via an NADPH-dependent process, and Ketoconazole (100μM) had no impact on this conversion. Additionally, the transport and metabolism of Seco Rapamycin in Caco-2 cell monolayers were examined. When Seco Rapamycin was administered to the apical compartment, minimal quantities were found in the basolateral compartment or cellular fractions after 4 hours, with negligible amounts of M2 detected. The presence of LY335979 minimally affected the distribution of Seco Rapamycin, although M2 was observed in the apical compartment under these conditions. Conversely, administration of Seco Rapamycin to the basolateral compartment resulted in detectable levels of both Seco Rapamycin and M2 in the apical compartment. Additionally, LY335679 reduced the movement of Seco Rapamycin to the apical compartment while increasing the presence of M2 in both compartments.