Article
Pharmacology & Pharmacy
Mirja Harms, Monica M. W. Habib, Simona Nemska, Antonella Nicolo, Andrea Gilg, Nico Preising, Pandian Sokkar, Sara Carmignani, Martina Raasholm, Gilbert Weidinger, Goenuel Kizilsavas, Manfred Wagner, Ludger Staendker, Ashraf H. Abadi, Hassan Jumaa, Frank Kirchhoff, Nelly Frossard, Elsa Sanchez-Garcia, Jan Muench
Summary: The EPI-X4 derivative JM#21 is a novel potent CXCR4 antagonist that shows therapeutic efficacy in atopic dermatitis and has demonstrated effectiveness in treating CXCR4-associated diseases, especially in asthma and other inflammatory conditions.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Chemistry, Medicinal
Sebastian Dekkers, Birgit Caspar, Joelle Goulding, Nicholas D. Kindon, Laura E. Kilpatrick, Leigh A. Stoddart, Stephen J. Briddon, Barrie Kellam, Stephen J. Hill, Michael J. Stocks
Summary: In this study, fluorescent probes based on previously reported small-molecule antagonists were designed and synthesized using classic medicinal chemistry approaches to investigate the pharmacology and cellular distribution of the CXCR4 receptor. Three distinct chemical classes of fluorescent probes were developed and shown to specifically bind to the CXCR4 receptor in a fluorescence-based NanoBRET binding assay (pKD ranging 6.6-7.1). These probes were also used in competition binding experiments and confocal microscopy to further explore the pharmacology and cellular distribution of CXCR4.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Jiachi Ma, Wanqing Liang, Yaosheng Qiang, Lei Li, Jun Du, Chengwu Pan, Bangling Chen, Chensong Zhang, Yuzhong Chen, Qingkang Wang
Summary: The study investigated the cooperative role of CXCR4/CXCL12 axis and IL-1Ra in the metastasis of colorectal cancer cells. It was found that IL-1 alpha and rIL-1 alpha promoted CXCL12 expression, while IL-1Ra inhibited this effect. Additionally, CXCL12 enhanced migration and proliferation of endothelial cells, and IL-1Ra inhibited migration, proliferation, and angiogenesis of colorectal cancer cells.
CELL COMMUNICATION AND SIGNALING
(2021)
Article
Chemistry, Multidisciplinary
Abraham Akonnor, Masaki Makise, Akihiko Kuniyasu
Summary: A CXCR4-targeted antitumor peptidomimetic (CTCE-KLAK) was developed and showed cell-selective cytotoxicity against breast cancer cells and induced rapid necrotic cell death. In a mouse model, CTCE-KLAK significantly inhibited tumor growth and lung metastasis, highlighting its potential as a promising agent for treating triple-negative breast cancer.
Article
Chemistry, Multidisciplinary
Dipankar Chaudhuri, Tiangong Lu, Binu Jacob, Sojan Abraham, Premlata Shankar, Michael A. Poss, Nouri Neamati, Julio A. Camarero
Summary: The CXCR4 chemokine is a crucial regulator of leukocyte functions, embryonic development, and cancer progression. CXCR4 antagonists show promise as therapeutic agents for cancer and HIV. This study shows that lipidation can improve the half-life of a bioactive cyclotide antagonist, but the choice of lipid may affect its biological activity.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Chemistry, Medicinal
Xiong Fang, Qian Meng, Huijun Zhang, Xiao Fang, Lina S. Huang, Xingquan Zhang, Robert T. Schooley, Aaron Ciechanover, Jing An, Yan Xu, Ziwei Huang
Summary: This study successfully designed and synthesized a new and potent small molecule CXCR4 antagonist, named HF51116. HF51116 exhibited very high CXCR4 binding affinity and inhibited SDF-1α-induced cell migration, calcium mobilization, and CXCR4 internalization. It also demonstrated inhibitory effects on HIV-1 infection via CXCR4. Analysis of the interaction between HF51116 and CXCR4 suggested that the compound recognizes the minor and major subpockets of CXCR4 and blocks G protein-dependent downstream signal pathways. HF51116 may serve as a prototype for developing CXCR4-targeted therapeutics.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
