Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China.
Anticancer Agents Med Chem. 2021;21(17):2368-2378. doi: 10.2174/1871520621666210202162953.
The Androgen Receptor (AR) signaling functionis a critical driving force for the progression of Prostate Cancer (PCa) to bring about anti-prostate cancer agents, and AR has been proved to be an effective therapeutic target even for Castration-Resistant Prostate Cancer (CRPC).
In order to discover novel anti-prostate cancer agents, we performed structural modifications based on the lead compounds T3 and 10e.
A set of 1-methyl- 1H-pyrazole-5-carboxamide derivatives were synthesized and evaluated for their inhibitory activities against both expressions of Prostate-Specific Antigen (PSA) and growth of PCa cell lines.
Compound H24 was found to be able to completely block PSA expression at 10μM, and showed prominent antiproliferative activity in both the LNCaP cell line (GI = 7.73μM) and PC-3 cell line (GI = 7.07μM).
These preliminary data supported a further evaluation of compound H24 as a potential agent to treat prostate cancer.
雄激素受体（AR）信号功能是前列腺癌（PCa）进展的关键驱动力，可用于开发抗前列腺癌药物，并且 AR 已被证明是一种有效的治疗靶点，即使对于去势抵抗性前列腺癌（CRPC）也是如此。
为了发现新型抗前列腺癌药物，我们对先导化合物 T3 和 10e 进行了结构修饰。
合成了一组 1-甲基-1H-吡唑-5-甲酰胺衍生物，并评估了它们对前列腺特异性抗原（PSA）表达的抑制活性和前列腺癌细胞系的生长抑制活性。
发现化合物 H24 能够在 10μM 时完全阻断 PSA 的表达，并在 LNCaP 细胞系（GI = 7.73μM）和 PC-3 细胞系（GI = 7.07μM）中表现出显著的增殖抑制活性。
这些初步数据支持进一步评估化合物 H24 作为治疗前列腺癌的潜在药物。
