Pyrimidine compounds BY4003 and BY4008 inhibit glioblastoma cells growth via modulating JAK3/STAT3 signaling pathway

• DOI: 10.1016/j.neurot.2024.e00431
• Publication Date: 2024-08-16T11:32:54Z
• Authors: Nisar Ahmad; Lixue Chen; Zixi Yuan; Xiaodong Ma; Xiaobo Yang; Yinan Wang; Yongshun Zhao; Huan Jin; Najib Khaidamah; Jinan Wang; Jiashuo Lu; Ziqi Liu; Moli Wu; Qian Wang; Yan Qi; Chong Wang; Yupu Zhao; Yang Piao; Rujie Huang; Yunpeng Diao; Sa Deng; Xiaohong Shu
• Keywords: STAT3 Transcription Factor; Brain Neoplasms; Janus Kinase 3; Apoptosis; Antineoplastic Agents; Pyrimidines; Piperidines; Cell Movement; Cell Line, Tumor; Humans; Original Article; Glioblastoma; Signal Transduction; Cell Proliferation

Glioblastoma (GBM) is a brain tumor characterized by its aggressive and invasive properties. It found that STAT3 abnormally activated in GBM, inhibiting signaling can effectively suppress progression. In this study, novel pyrimidine compounds, BY4003 BY4008, were synthesized to target the JAK3/STAT3 pathway, their therapeutic efficacy mechanisms of action evaluated compared with Tofacitinib U251, A172, LN428 patient-derived glioblastoma cells. The ADP-Glo™ kinase assay was utilized assessed inhibitory effects BY4008 on JAK3, crucial member JAK family. results showed both compounds significantly inhibited JAK3 enzyme activity, IC