Rapamycin

Rapamycin (Sirolimus; AY 22989) is a potent and specific blood-brain barrier-transmissible mTOR inhibitor with an IC₅₀ of 0.1 nM in HEK293 cells. Rapamycin binds to FKBP12 and specifically acts as an allosteric inhibitor of mTORC1^[1]. Rapamycin is an autophagy activator, an immunosuppressant^[2]. IC50 & Target:IC50: 0.1 nM (mTOR)^[1] In Vitro:Rapamycin (12.5-100 nM; 24 hours) treatment exerts modest inhibitory effect on lung cancer cell proliferation in a dose-dependent manner in all cell lines (A549, SPC-A-1, 95D and NCI-H446 cells) tested, achieving about 30-40% reduction in cell proliferation at 100 nM vs. ~10% reduction at 12.5 nM^[3].
Lung cancer cell line 95D cells are exposed to Rapamycin (10 nM, 20 nM) and RP-56976 (1 nM, 10 nM) alone or in combination (Rapamycin 20 nM+ RP-56976 10 nM). After 24 hours exposure to Rapamycin or RP-56976 alone does not significantly alter the level of expression or phosphorylation of ERK1/2, whereas cells treated with the combination of Rapamycin with RP-56976 exhibit a marked reduction in the phosphorylation levels of ERK1/2^[3]. In Vivo:Rapamycin (2.0 mg/kg; intraperitoneal injection; every other day; 28 days) alone has a moderate inhibitory effect. However, the combination of Metformin (HY-B0627) and Rapamycin exerts a significantly increased inhibition of tumor growth compared with the control group, the Rapamycin monotherapy group and the Metformin monotherapy group^[4].