While the specific s-EH inhibitors used in the early academic studies did not have favorable drug-like features, they provided convincing proof-of-concept (POC) in a preclinical setting. Based on this background, Arête’s objective was to industrialize this academic research and discover novel s-EH inhibitors that not only retain the inhibitory potency of the literature compounds but in addition have good drug-like ADME, PK, and safety properties, thereby making them suitable candidates for preclinical and clinical development.

To date, Arête has developed various proprietary in vitro, ex vivo, and in vivo assays as part of its screening funnel and has identified several chemical classes of novel s-EH inhibitors that are in various stages of preclinical and clinical development for a variety of disease indications, including hypertension, metabolic syndrome and inflammation.

In addition to its phase 1 clinical development candidate AR9281, the company is testing several potential back-up candidates as additional first-in-class anti-hypertensive plus agents.

In addition to anti-hypertensive effects, Arête is conducting preclinical studies for s-EH inhibitors targeting metabolic syndrome. In animal models of obesity, Arête’s compounds improved glucose handling and decreased weight gain, cholesterol, and adipose tissue weight.

Arête is evaluating additional market opportunities, as inhibitors of s-EH could be useful in the prevention of atherosclerotic plaque rupture and treatment of skin diseases, erectile dysfunction, and diabetic nephropathy.