Mammalian target of rapamycin (mTOR) inhibitors with therapeutic potential for colitis

Abstract

Mammalian target of rapamycin (mTOR) is a protein kinase that regulates cell proliferation and protein synthesis in response to mitogens and nutrients. A plethora of recent research has linked increased mTOR activity to heightened inflammatory responses. Many of these findings suggest that mTOR inhibitors may be useful for treatment of ulcerative colitis (UC)^1,2. The discovery, synthesis and a SAR of new cyano-pyridyl based small molecule inhibitor which suppresses DSS-induced colitis by inhibiting T cell function³is discussed. The most potent small molecule inhibitor of mTOR did not inhibit PI3K/Akt phosphorylation and thus turned out to be mTOR selective.