JNJ-101556143

JNJ-101556143 is an investigational, orally bioavailable small molecule inhibitor of the cytochrome P450 enzyme CYP11A1 (cholesterol side-chain cleavage enzyme), developed by Janssen Research & Development. CYP11A1 catalyzes the conversion of cholesterol to pregnenolone, which is the initial and rate-limiting step in the biosynthesis of all steroid hormones, including androgens, estrogens, and glucocorticoids. By targeting this bottleneck enzyme, JNJ-101556143 achieves a comprehensive suppression of steroidogenesis, a strategy sometimes referred to as medical adrenalectomy. This approach is intended to treat advanced prostate cancers, such as metastatic castration-resistant prostate cancer (mCRPC) and metastatic hormone-sensitive prostate cancer (mHSPC), by eliminating the production of extragonadal and intratumoral androgens that contribute to disease progression and resistance to conventional androgen deprivation therapies. It is currently being evaluated in Phase 1 clinical trials both as a monotherapy and in combination with other novel agents like pasritamig.