mTORC1-IN-3 is a potent and selective inhibitor of mTORC1, with an IC50 value of 26.38 μM. It specifically inhibits the phosphorylation of mTORC1 substrates without affecting mTORC2 substrate phosphorylation. mTORC1-IN-3 can reduce intracellular lipid accumulation and induce autophagy (autophagy). This compound is applicable in research related to cancer, immunology, metabolic disorders, and neurological diseases such as diabetes and Alzheimer's disease.

mTORC1:26.38 μM

mTORC1-IN-3 (Compound TCG3) at a concentration of 10 μM over 2 hours selectively inhibits the phosphorylation of mTORC1 substrates p-p70S6K (Thr389), p-S6 (Ser235/236), and p-4E-BP1 (Thr37/46) in HepG2 cells and primary mouse hepatocytes, without affecting mTORC2 substrate p-Akt(Ser473) phosphorylation. At the same concentration but over 24 hours, mTORC1-IN-3 inhibits AMPK-mediated phosphorylation of ULK1 (Ser757), reducing ULK1 activation and inducing the early stages of autophagy in HepG2 cells. Furthermore, it decreases lipid droplet accumulation induced by fatty acids in HepG2 cells. With concentrations ranging from 1 to 30 μM over 24 hours, mTORC1-IN-3 exhibits low cytotoxicity in HepG2 cells. It also consistently inhibits the phosphorylation of mTORC1 substrates in HEK293T, JURKAT, and 786-O cells when used at 10 μM for 24 hours.

mTORC1-IN-3 (Compound TCG3) administered at 15 mg/kg via intraperitoneal injection, 30 minutes prior to insulin injection, effectively reverses insulin-induced hypoglycemia in C57BL/6 mice.