CYP Inhibitors PLatform
Through molecular modeling and rational drug design, we have built a proprietary platform to create highly specific libraries of inhibitors of cytochrome P450 (“CYP”) enzymes. The cytochrome P450 family of proteins includes enzymes responsible for the metabolism of drugs and ingested toxic substances and enzymes responsible for the metabolism of endogenous substances such as steroids, vitamins and lipids. We have modified and tailored our compounds for selectivity to inhibit specific enzymes. By thus modulating the activity of specific endogenous signal transduction pathways, we have the opportunity to target different diseases in which those pathways are implicated.
Our most advanced CYP inhibitor program is targeted towards aldosterone synthase (CYP11B2), with inhibitors being evaluated as a potential treatment for chronic kidney disease and hypertension. Compound ANG3586 is selective for aldosterone synthase (over the closely related enzyme CYP11B1) and has shown activity in preclinical animal models of chronic kidney disease and polycystic kidney disease. More selective compounds have been identified and are undergoing IND-enabling studies.
As a product of Angion’s proprietary CYP inhibitor platform, we have also identified compounds that predominantly inhibit CYP11B1 as cortisol lowering agents for potential use in Cushing’s syndrome patients.
Another Angion CYP inhibitor targets retinoic acid hydroxylase, encoded by the CYP26 genes. This CYP is responsible for metabolizing retinoic acid, an endogenous molecule with beneficial activities in many diseases as well as in maintaining the integrity of skin. Retinoic acid is present in some anti-wrinkle creams, but it has toxic side effects. By inhibiting CYP26 in the skin, the body’s endogenous levels of retinoic acid can be elevated to benefit the skin without the side effects of applied retinoic acid. Angion licensed the rights to one CYP26 inhibitor, ANG3522, to a privately-held dermatology company for use in dermatological indications, in both cosmetic and prescription products.