X-414 Selective Small Molecule mTOR Inhibitor

Mammalian target of rapamycin (mTOR) is a serine/threonine kinase which is downstream in the PI3K pathway that plays a critical role in cell proliferation and angiogenesis.  mTor is present is two distinct protein complexes, mTORC1 and mTORC2.  These two complexes phosphorylate different substrates to regulate distinct cellular functions.  mTORC1 has been shown to play a role in cell survival and cytoskeletal organization.  On the other hand, mTORC2 stimulates cell growth and proliferation.  Through abnormal activation, both complexes of mTOR appear to play a pivital role in cellular growth and proliferation of cancer.  mTOR is a clinically validated target in the treatment of cancer including renal cell carcinomas and some non Hodgkin lymphomas.

Xcovery has also developed a potent mTOR small molecule kinase inhibitor, X-414, that targets both complexes but does not inhibit PI3K. As a selective mTor inhibitor, X-414 may circumvent some of the toxicity associated with PI3K inhibition. Also, by hitting both complexes of the mTOR protein, X-414 can prevent the resistance loophole.  X-414 show significant tumor regression without inducing toxicity in preclinical models.