CCT365623 hydrochloride (C09-1120-890)

CCT365623 hydrochloride is an orally active lysyl oxidase (LOX) inhibitor, with an IC 50 of 0.89 μM. CCT365623 hydrochloride suppresses EGFR (pY1068) and AKT phosphorylation driven by EGF . CCT365623 hydrochloride is extremely well tolerated, and has good pharmacokinetic propertiesIn VitroCCT365623 inhibits LOX at ~5 μM in the biosensor system. CCT365623 (0-40 μM) concentration-dependently decreases the protein levels of surface EGFR. CCT365623 (5 μM) decreases the protein levels of pY1068 EGFR, pAKT and MATN2, and increases the protein levels of pSMAD2. CCT365623 disrupts HTRA1 multimerization, activates TGFβ1 signalling, suppresses MATN2 expression, suppresses EGFR surface retention, and suppresses EGFR signalling. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: MDA-MB-231 cells. Concentration: 0-40 μM. Incubation Time: 24 hours Result: Significantly decreased the protein levels of surface EGFR, pY1068 EGFR, pAKT and MATN2. Increased the protein levels of pSMAD2.In VivoCCT365623 displays good stability in mouse liver microsomes and does not inhibit the cardiac potassium channel hERG . 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 cell . CCT365623 exhibits a T 1/2 PO of 0.6 h and F% (oral bioavailability) of 45% . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Mouse model of spontaneous breast cancer that metastasizes to the lungs (70 days old) . Dosage: 70 mg/kg. Administration: Oral gavage per day for about 3 weeks. Result: Significantly reduced MATN2 protein levels in both the primary and metastatic lung tumors and this is accompanied by the loss of EGFR from the plasma membranes of the cells in both the primary and metastatic tumors.Form:SolidIC50& Target:IC50: 0.89 μM (LOX). Specification: 0.98 Molecular Formula: C18H18ClNO4S3 Molecular Weight: 443.99 PubChem CID: 139266765