Rapamycin

Sirolimus; AY-22989

914.17

H2O : < 0.1 mg/mL (insoluble); DMSO : 125 mg/mL (136.74 mM; Need ultrasonic); Ethanol : 50 mg/mL (54.69 mM; Need ultrasonic)

Cancer

Fungal, mTOR, Autophagy, Endogenous Metabolite, FKBP, FKBP, FKBP, Antibiotic

Rapamycin (Sirolimus; AY 22989) is a potent and specific 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. ca.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 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].