CXL-1020

CXL-1020 is a hydroxylamine-based nitroxyl (HNO) donor. CXL-1020 improves cardiac inotropy/lusitropy and Ca2+ cycling in rats with abnormal relaxation. CXL-1020 induces vasorelaxation and improves cardiac function in canine models. CXL-1020 has been used to research systolic heart failure and stable heart failure[1].

Signaling Pathways >> Membrane Transporter/Ion Channel >> Calcium Channel

Research Areas >> Cardiovascular Disease

L-type calcium channel

CXL-1020 (100 μg/kg/min; infusion for 30 min) improves hemodynamics and cardiac function, and enhances both diastolic and systolic performance in mice[1]. CXL-1020 (3 and 10 mg/kg/min; 4-hour intravenous infusion) improves left ventricular systolic and diastolic function in dogs with advanced heart failure[2]. Animal Model: Adult male Sprague-Dawley rats (250-350 g; induced cardiac dysfunction by isoproterenol)[1] Dosage: 100 μg/kg/min Administration: For 30 min Result: Improved hemodynamics and cardiac function in normal rats, and enhanced both diastolic and systolic performance in cardiac dysfunction mice. Animal Model: Dogs (coronary microembolization-induced heart failure)[2]3 and 10 mg/kg/min Dosage: 3 and 10 mg/kg/min Administration: 4-hour intravenous infusion Result: Decreased systolic aortic pressure (AoP) modestly; significantly increased EF and deceleration time of early mitral inflow velocity (DT) and significantly lowered left ventricular (LV) end-systolic volume (ESV), LV end-diastolic pressure (EDP) and end-diastolic wall stress (EDWS) in a dose-dependent manner.

[1]. Roof SR, et al. CXL-1020, a Novel Nitroxyl (HNO) Prodrug, Is More Effective than Milrinone in Models of Diastolic Dysfunction-A Cardiovascular Therapeutic: An Efficacy and Safety Study in the Rat. Front Physiol. 2017 Nov 10;8:894.

[2]. Mengjun Wang, et al. Intravenous Infusion of CXL-1020, a Novel Nitroxyl (HNO) Donor, Improves Left Ventricular Systolic and Diastolic Function in Dogs with Advanced Heart Failure. CARDIOVASCULAR PHARMACOLOGY. VOLUME 15, ISSUE 6, SUPPLEMENT, S73-S74, AUGUST 01, 2009.