Sapanisertib

Sapanisertib (INK-128; MLN0128; TAK-228) is an orally available, ATP-dependent mTOR1/2 inhibitor with an IC₅₀ of 1 nM for mTOR kinase. IC50 & Target: IC50: 1 nM (mTOR), 219 nM (PI3Kα), 5293 nM (PI3Kβ), 230 nM (PI3Kδ), 221 nM (PI3Kγ)^[2]
Ki: 1.4 nM (mTOR), 152 nM (PI3Kα), 4700 nM (PI3Kβ), 165 nM (PI3Kγ)^[2] In Vitro: Sapanisertib (INK-128) exhibits an enzymatic inhibition activity against mTOR and more than 100-fold selectivity to PI3K kinases^[1]. Sapanisertib (INK-128) selectively decreases the expression of YB1, MTA1, vimentin and CD44 at the protein but not transcript level in PC3 cells. Sapanisertib (INK-128) decreases the invasive potential of PC3 prostate cancer cells. Furthermore, Sapanisertib (INK-128) inhibits cancer cell migration starting at 6 h of treatment, precisely correlating with when decreases in the expression of pro-invasion genes are evident, but preceding any changes in the cell cycle or overall global protein synthesis^[2]. In Vivo: In a ZR-75-1 breast cancer xenograft model, Sapanisertib (INK-128) shows tumor growth inhibition efficacy at a dose of 0.3 mg/kg/day^[1]. 4EBP1 and p70S6K1/2 phosphorylation is completely restored to wild-type levels after treatment with INK128 in PtenL/L mice. Sapanisertib (INK-128) treatment results in a 50% decrease in prostatic intraepithelial neoplasia (PIN) lesions in PtenL/L mice and induces programmed cell death in multiple cancer cell lines in mice^[2].