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Irreversible Dual Inhibitory Mode: The Novel Btk Inhibitor Pls-123 Demonstrates Promising Anti-Tumor Activity In Human B-Cell Lymphoma., Ning Ding, Xitao Li, Yunfei Shi, Lingyan Ping, Lina Wu, Kai Fu, Lixia Feng, Xiaohui Zheng, Yuqin Song, Zhengying Pan, Jun Zhu

Journal Articles: Pathology and Microbiology

The B-cell receptor (BCR) signaling pathway has gained significant attention as a therapeutic target in B-cell malignancies. Recently, several drugs that target the BCR signaling pathway, especially the Btk inhibitor ibrutinib, have demonstrated notable therapeutic effects in relapsed/refractory patients, which indicates that pharmacological inhibition of BCR pathway holds promise in B-cell lymphoma treatment. Here we present a novel covalent irreversible Btk inhibitor PLS-123 with more potent anti-proliferative activity compared with ibrutinib in multiple cellular and in vivo models through effective apoptosis induction and dual-action inhibitory mode of Btk activation. The phosphorylation of BCR downstream activating AKT/mTOR and MAPK signal pathways …