A Highly Selective and Potent CXCR4 Antagonist for Hepatocellular Carcinoma Treatment
A highly selective and potent CXCR4 antagonist for hepatocellular carcinoma treatment Jen-Shin Songa,1, Chih-Chun Changb,1, Chien-Huang Wua,1, Trinh Kieu Dinhb, Jiing-Jyh Jana, Kuan-Wei Huangb, Ming-Chen Choua, Ting-Yun Shiueb, Kai-Chia Yeha, Yi-Yu Kea, Teng-Kuang Yeha, Yen-Nhi Ngoc Tab, Chia-Jui Leea, Jing-Kai Huanga, Yun-Chieh Sungb, Kak-Shan Shiaa,2, and Yunching Chenb,2 aInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 35053, Taiwan, Republic of China; and bInstitute of Biomedical Engineering and Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, 30013 Hsinchu, Taiwan, Republic of China Edited by Michael Karin, University of California San Diego, La Jolla, CA, and approved February 4, 2021 (received for review July 23, 2020) The CXC chemokine receptor type 4 (CXCR4) receptor and its ligand, advanced HCC (9, 17), the concept of which has been experimentally CXCL12, are overexpressed in various cancers and mediate tumor validated by the discovery of a CXCR4 antagonist, BPRCX807. progression and hypoxia-mediated resistance to cancer therapy. AMD3100 was the first Food and Drug Administration (FDA)- While CXCR4 antagonists have potential anticancer effects when approved CXCR4 antagonist used for peripheral blood stem cell combined with conventional anticancer drugs, their poor potency transplantation (PBSCT) (18); however, its application to solid against CXCL12/CXCR4 downstream signaling pathways and sys- tumors is limited by its poor pharmacokinetics and toxic adverse temic toxicity had precluded clinical application. Herein, BPRCX807, effects after long-term administration (19, 20). Thus, a CXCR4 known as a safe, selective, and potent CXCR4 antagonist, has been antagonist with higher safety and better pharmacological and designed and experimentally realized.
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