P2, N=130, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

P1/2, N=76, Recruiting, Novartis Pharma AG | Not yet recruiting --> Recruiting

P1/2, N=46, Recruiting, Novartis Pharma AG

P1/2, N=76, Not yet recruiting, Novartis Pharma AG

P1, N=15, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

P1/2, N=188, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

P1/2, N=188, Not yet recruiting, Novartis Pharmaceuticals

P1, N=15, Not yet recruiting, Novartis Pharmaceuticals

The androgen deprivation therapy (ADT) alone and its combination with hormone therapy that block AR signaling (e.g., enzalutamide or abiraterone) are effective treatments for advanced prostate cancer. No animal was found dead or moribund and no test article-related changes in clinical signs,body weights, food consumption, ophthalmologic examinations, clinical pathology parameters, sperm analysis, urinalysis, organ weights, histopathology. In conclusion, HSK38008 is a promising oral AR-V7 degrader with better efficacy than enzalutamide and ARV-110 in AR and AR-V7 positive, and potential AR mutants mCRPC.

It is activated by the binding of androgenic hormones and transcriptionally regulates multiple genes including the ones that regulate cell cycle. Using HiBiT CRISPR cell line, biochemical methods, and RNA sequencing, we report the potential role of VNPP433-3β, the next generation galeterone analog as molecular glue that brings together AR, the key driver of prostate cancer and MDM2, an E3 ubiquitin ligase leading to ubiquitination and subsequent degradation of f-AR and AR-V7 in prostate cancer cells.

Au-AR pep-PROTAC results in suppression of AR levels and induces tumor regression in both enzalutamide sensitive and resistant prostate cancer animal models. Further optimization of the Au-AR pep-PROTAC can ultimately lead to a new therapy for AR-V7-positive CRPC.

Earlier, we developed drug candidate galeterone, which advanced through phase 2-clinical trials in treating castration-resistant PCa (CRPC)...Finally, RNA-seq demonstrates modulation of multiple pathways that synergistically contribute to PCa inhibition. Therefore, VNPP433-3β exerts its antitumor effect by imposing 1) transcriptional regulation of AR and AR-responsive oncogenes 2) translational regulation by disrupting mRNA-5'cap-dependent translation initiation, 3) reducing AR half-life through enhanced proteasomal degradation in vitro and AR-overexpressing tumor xenografts in vivo.