CXL 1020

CXL 1020 is an experimental drug that is being investigated as a treatment for acute decompensated heart failure. CXL 1020 functions as a nitroxyl donor; nitroxyl is the reduced, protonated version of nitric oxide. Nitorxyl is capable of enhancing left ventricular contractility without increasing heart rate by modifying normal Ca²⁺ cycling through the sarcoplasmic reticulum as well as increasing the sensitivity of cardiac myofilaments to Ca²⁺.

Acute decompensated heart failure

Patients with acute decompensated heart failure have diminished left ventricular systolic and/or diastolic functioning. Impaired ventricular function can be a consequence of decreased sarcoplasmic reticulum Ca²⁺ cycling and a corresponding decline in cardiomyocyte contraction. Reduced ventricular functioning limits the ability of the ventricles to fill with blood and pump blood to the rest of the body.

Sarcoplasmic reticulum Ca²⁺ Cycling

There are two mechanisms through which CXL 1020 is able to enhance the movement of Ca²⁺ in and out of the sarcoplasmic reticulum. Sarcoplasmic reticulum CaATPase (SERCA) is an energy-dependent ion pump found the sarcoplasmic reticulum of cardiac myocytes that is responsible for transporting Ca²⁺ within the cytosol back in to the lumen of the sarcoplasmic reticulum. The nitroxyl group that is donated by CXL 1020 initiates glutathiolation of SERCA at the cysteine 674 site, which in turn activates ATP-dependent Ca2+ transport. Therefore, stimulation of SERCA leads to accelerated uptake of Ca²⁺ from the cytosol of the cardiac myocyte.

CXL

CXL may refer to: