Pyridine indole hybrids as novel potent CYP17A1 inhibitors.

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Tác giả: Fredrik Björkling, Therina du Toit, Angelika Grudzińska, Jeremiah C Harrington, Flemming Steen Jørgensen, Amit V Pandey, Katyayani Sharma, Tomasz M Wróbel, Jibira Yakubu

Ngôn ngữ: eng

Ký hiệu phân loại: 770.233 Photography as a hobby

Thông tin xuất bản: England : Journal of enzyme inhibition and medicinal chemistry , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 58221

Prostate cancer (PCa) is one of the most prevalent malignancies affecting men worldwide, and androgen deprivation therapy (ADT) is a primary treatment approach. CYP17A1 inhibitors like abiraterone target the steroidogenic pathway to reduce androgen levels, but their clinical efficacy is limited by drug resistance and adverse effects. This study reports the synthesis and evaluation of novel CYP17A1 inhibitors derived from a previously identified hit compound. Several analogs were synthesised, including an unexpected di-cyano derivative, which demonstrated increased potency against CYP17A1 compared to abiraterone. Biological assays revealed that these compounds significantly inhibited CYP17A1 enzymatic activity and altered steroid biosynthesis. Among the newly synthesised inhibitors, compound
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