KAR-5585

Rodatristat ethyl (KAR5585) is an orally active tryptophan hydroxylase 1 (TPH1) inhibitor with nanomolar in vitro potency. Rodatristat ethyl reduces the level of 5-HT and significantly reduces pulmonary arterial hypertension (PAH)[1][2].

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Metabolic Enzyme/Protease >> Tryptophan Hydroxylase

Rodatristat ethyl (100 or 200 mg/kg; oral administration; once daily; for 28 days; male Sprague-Dawley rats) treatment decreases erum, gut and lung 5-HT levels in a dose-dependent manner and significantly reduces pulmonary arterial pressure, and pulmonary vessel wall thickness and occlusion in male rats with monocrotaline (MCT)[1]. Animal Model: Male Sprague-Dawley rats (175-200 g)[1] Dosage: 100 mg/kg or 200 mg/kg Administration: Oral administration; once daily; for 28 days Result: Decreased serum, gut and lung 5-HT levels in a dose-dependent manner and significantly reduced pulmonary arterial pressure, and pulmonary vessel wall thickness and occlusion in male rats.

[1]. Aiello RJ, et al. Tryptophan hydroxylase 1 Inhibition Impacts Pulmonary Vascular Remodeling in Two Rat Modelsof Pulmonary Hypertension. J Pharmacol Exp Ther. 2017 Feb;360(2):267-279.

[2]. Alice Melão, MSc. Early Results on Rodatristat Ethyl Support Launch of Phase 2 Trial in PAH Patients. FEBRUARY 4, 2019.