Design, synthesis and activity evaluation of protein arginine methyltransferase 5 inhibitor / 药学学报
Acta Pharmaceutica Sinica
; (12): 1859-1871, 2020.
Article
ي Zh
| WPRIM
| ID: wpr-825177
المكتبة المسؤولة:
WPRO
ABSTRACT
Protein arginine methyltransferase 5 (PRMT5) is an important type II human methyltransferase. It catalyzes the symmetrical double-methylation of many histones and non-histones, and it is highly expressed in many kinds of tumors. PRMT5 has been proven to be a potential new target for cancer treatment. Based on the reported crystal complex of EPZ015666 with PRMT5, a series of new compounds was designed using GSK3326595 (EPZ015938) as the lead compound and using the conformational restriction approach. We found that compounds B8 and the C series of derivatives displayed enzyme inhibitory activity comparable to that of GSK3326595. Compounds C3 and C4 showed poor permeability in Caco-2 cells, and that might be one of the reasons for their poor anti-proliferative activity against Z-138 cells. These data provide insights for further structural optimization.
النص الكامل:
1
الفهرس:
WPRIM
اللغة:
Zh
مجلة:
Acta Pharmaceutica Sinica
السنة:
2020
نوع:
Article