Drug repurposing for renin inhibition: identifying panobinostat for hypertension management.

Renin, an aspartyl protease enzyme, is a crucial part of the renin-angiotensin-aldosterone system (RAAS) that regulates blood pressure. However, numerous renin inhibitors, including Aliskiren, Zankiren, Enalkiren, Fasidotril, and Remikiren, are in the clinical arena of managing hypertension, but they are associated with numerous drawbacks. The important one includes modest efficacy in contrast to other antihypertensive agents, which reduces their use as monotherapy; secondly, the related side effects, including hyperkalemia and renal impairment. Thus, considering the unmet need to identify new renin inhibitors, we applied the drug repurposing technique on an 1880 US FDA-approved small molecules database. The research was achieved by performing the structure-based virtual screening (SBVD) on FDA-approved drugs, which was well supported by molecular docking, dynamics, and mechanics studies. This work identified Panobinostat as a possible lead renin inhibitor. The in vitro Elisa-based assay revealed Panobinostat has the potential to inhibit the renin enzyme at the half-maximal concentration (IC