CCT365623 hydrochloride is an orally active inhibitor of lysyl oxidase (LOX) (IC50: 0.89 μM). It suppresses EGFR (pY1068) and AKT phosphorylation driven by EGF.

LOX:0.89 μM

CCT365623 inhibits LOX at ~5 μM in the biosensor system. CCT365623 (0-40 μM) concentration-dependently decreases the protein levels of surface EGFR. CCT365623 disrupts HTRA1 multimerization, activates TGFβ1 signaling, suppresses MATN2 expression, suppresses EGFR surface retention, and suppresses EGFR signaling. CCT365623 (5 μM) decreases the protein levels of pY1068 EGFR, pAKT, and MATN2, and increases the protein levels of pSMAD2.

CCT365623 (70 mg/kg, oral gavage per day) significantly delays the development of the primary tumors and also suppresses metastatic lung burden in the animals. CCT365623 disrupts EGFR cell surface retention and delays the growth of primary and metastatic tumor cells. CCT365623 exhibits a T1/2PO of 0.6 h and F% (oral bioavailability) of 45%.