KXO1: The first non-ATP competitive Src inhibitor for clinical development in oncology applications-2

MEDI 232

David G Hangauer, dhangauer@kinexpharma.com1, Irwin Gelman2, Lyn Dyster1, Allen Barnett1, Michael Smolinski1, Taher Hegab1, and Lingqiu Gao2. (1) Kinex Pharmaceuticals, New York State Center of Excellence in Bioinformatics & Life Sciences, 701 Ellicott St., Buffalo, NY 14203, (2) Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263
Utilizing Kinex Pharmaceuticals platform technology, MimeticaTM, KXO1 was discovered as a novel small molecule Src tyrosine kinase inhibitor. KXO1 targets the peptide substrate binding site rather than the ATP site wherein most tyrosine kinase inhibitors bind. This unique binding site provides much higher selectivity than is obtained with ATP competitive Src inhibitors. KXO1 inhibits Src kinase activity in whole cells with low nM potency and is >1,000-fold less active against other tyrosine kinases such as EGFRTK, PDGFRTK, JAK1, JAK2, ZAP70 and Lck. KXO1 is also a low nM potency inhibitor of cancer cell growth for a broad range of solid tumor and leukemia cancer cell types in vitro, and is orally effective in animal tumor models. KXO1 has successfully completed preclinical development for oncology applications and will be the first non-ATP competitive Src inhibitor to enter clinical trials.