In vitro activity: ASK1-IN-1 is a potent inhibitor of the apoptosis signal regulating kinase 1 (ASK1) inhibitor (Compound 4 from patent WO2016025474A1). It dose-dependently decreases pulmonary arterial pressure and right ventricular (RV) hypertrophy in an in vivo pulmonary hypertension (PH) model. Inhibition of ASKl can reduce the hallmarks of pulmonary vascular disease including and not limited to reduced pulmonary vascular resistance (PVR), improved pulmonary pressure, decreased pulmonary vascular remodeling, improved vascular function, decreased maladaptive RV hypertrophy, and improved RV function. Inhibition of ASKl signaling may also slow, prevent, and/or reverse pathological changes associated with PH.

Kinase Assay: ASKl inhibition reduces hallmarks of pulmonary vascular disease including and not limited to reduce pulmonary vascular resistance (PVR), improve pulmonary pressure, decreased pulmonary vascular remodeling, improved vascular function, decrease maladaptive RV hypertrophy, and improve RV function. Inhibition of ASKl signaling may slow, prevent, and/or reverse pathological changes associated with PH. Plasma levels of B-type natriuretic peptide (BNP) are reduced by both doses of ASK1-IN-1: 0.1+0.05 for 0.1% and 0.1±0.1 ng/mL for 0.2%. Su/Hx rats treated with 0.1 % or 0.2% ASK1-IN-1 has a decreased number of completely muscularized arterioles (35.6% and 32.6%, respectively)

Cell Assay: ASKl inhibition reduces hallmarks of pulmonary vascular disease including and not limited to reduce pulmonary vascular resistance (PVR), improve pulmonary pressure, decreased pulmonary vascular remodeling, improved vascular function, decrease maladaptive RV hypertrophy, and improve RV function. Inhibition of ASKl signaling may slow, prevent, and/or reverse pathological changes associated with PH. Plasma levels of B-type natriuretic peptide (BNP) are reduced by both doses of ASK1-IN-1: 0.1+0.05 for 0.1% and 0.1±0.1 ng/mL for 0.2%. Su/Hx rats treated with 0.1 % or 0.2% ASK1-IN-1 has a decreased number of completely muscularized arterioles (35.6% and 32.6%, respectively)