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

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 function 3 is discussed. The most potent small molecule inhibitor of mTOR did not inhibit PI3K/Akt phosphorylation and thus turned out to be mTOR selective.