DS9051

DS9051 is an orally bioavailable targeted protein degrader (TPD) developed by Daiichi Sankyo. It is designed to selectively target and degrade Cytochrome P450 11B1 (CYP11B1), also known as 11β-hydroxylase, an enzyme critical for steroidogenesis that is frequently overexpressed in adrenocortical carcinoma (ACC) and plays a role in the progression of metastatic castration-resistant prostate cancer (mCRPC). By leveraging the ubiquitin-proteasome system, DS9051 acts as a molecular bridge between the target protein and an E3 ubiquitin ligase, leading to the ubiquitination and subsequent proteasomal degradation of CYP11B1. This mechanism aims to deplete the intracellular pool of the enzyme, thereby inhibiting the production of steroids that drive tumor growth. It is currently being evaluated in Phase 1 clinical trials for patients with advanced ACC or mCRPC.