Design, synthesis, and biological evaluation of indazole-based PLK4 inhibitors

Cunzheng Fan, Nian Liu, Ningyuan Hu, Minghui Tong, Xuan Shi, Han Wang, Wenqiang Sun, Zehui Qi, Haoyu Zhang, Yixiang Sun, Zixuan Gao, Dongmei Zhao and Maosheng Cheng

RSC Med. Chem., 2025,16, 5717-5735

Abstract

Polo-like kinase 4 (PLK4), a member of the serine/threonine protein kinase family, serves as a central regulator of centriole duplication and plays a critical role in eukaryotic mitosis.

Design, synthesis, and biological evaluation of novel N-(1H-indazol-6-yl)benzenesulfonamide derivatives as potent PLK4 inhibitors

Pengkun Sun, Cunzheng Fan, Nian Liu, Minghui Tong, Xuan Shi, Han Wang, Shuyi Mu, Ningyuan Hu, Yixiang Sun, Haoyu Zhang, Zixuan Gao, Dongmei Zhao and Maosheng Cheng

RSC Med. Chem., 2025,16, 3551-3566

From themed collection: Highlights from Industry

Abstract

PLK4 is a serine/threonine protein kinase situated at the centrosome, acting as a crucial regulatory element in the regulation of cell mitosis and significantly contributing to the preservation of genomic integrity.

Design, synthesis, and biological evaluation of 5-chlorine-2-amino-pyrimidine derivatives as potent PLK4 inhibitors

Shuyi Mu, Wenqiang Sun, Zehui Qi, Minghui Tong, Xuan Shi, Han Wang, Nian Liu, Pengkun Sun, Cunzheng Fan, Ningyuan Hu, Yixiang Sun, Haoyu Zhang, Zixuan Gao, Dongmei Zhao and Maosheng Cheng

RSC Med. Chem., 2025,16, 4997-5011

Abstract

Serine/threonine kinase PLK4, a critical regulator of centrosome duplication, is closely associated with tumorigenesis due to its role in centrosome amplification.

Design, synthesis and biological evaluation of pyrazolo[3,4-b]pyridine derivatives as TRK inhibitors

Nian Liu, Xin Wang, Qinglin Fu, Qiaohua Qin, Tianxiao Wu, Ruicheng Lv, Dongmei Zhao and Maosheng Cheng

RSC Med. Chem., 2023,14, 85-102

Abstract

Based on scaffold hopping and computer-aid drug design, 38 pyrazolo[3,4-b]pyridine derivatives were synthesised. Among them, compound C03 showed acceptable activity with an IC₅₀ value of 56 nM to TRKA kinase.

Synthesis, in silico and in vitro studies of aminopyrimidine hybrids as EGFR TK inhibitors and anti-proliferative agents

Wael Shehta, Basant Farag, Shaker Youssif, Samar El-Kalyoubi and Sherin M. Elfeky

RSC Adv., 2025,15, 36895-36906

Abstract

Two pyrimidine hybrid series (6a–g, 10a–d) were synthesized. Compounds 6c and 10b showed anti-proliferative activity against MCF-7, strong EGFR-TK inhibition, and docking confirmed effective binding. In silico studies suggest safe, orally bioavailable candidates.