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CXCL12/CXCR4: a symbiotic bridge linking cancer cells and their stromal neighbors in oncogenic communication networks.CXCL12/CXCR4：致癌通讯网络中连接癌细胞与其基质邻域的共生桥梁。
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3
CXCR4 inhibition in tumor microenvironment facilitates anti-programmed death receptor-1 immunotherapy in sorafenib-treated hepatocellular carcinoma in mice.肿瘤微环境中的CXCR4抑制可促进索拉非尼治疗的小鼠肝细胞癌中的抗程序性死亡受体-1免疫治疗。
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Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer.针对富含纤维母细胞激活蛋白（FAP）的癌相关成纤维细胞中的 CXCL12 进行靶向治疗，与抗 PD-L1 免疫疗法联合应用于胰腺癌。
Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20212-7. doi: 10.1073/pnas.1320318110. Epub 2013 Nov 25.
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Pharmacologically antagonizing the CXCR4-CXCL12 chemokine pathway with AMD3100 inhibits sunlight-induced skin cancer.用 AMD3100 抑制 CXCR4-CXCL12 趋化因子通路的药理学作用可抑制阳光诱导的皮肤癌。
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具有刚性侧链的新型四氢异喹啉CXCR4拮抗剂的合成

Synthesis of Novel Tetrahydroisoquinoline CXCR4 Antagonists with Rigidified Side-Chains.

作者信息

Jecs Edgars, Miller Eric J, Wilson Robert J, Nguyen Huy H, Tahirovic Yesim A, Katzman Brook M, Truax Valarie M, Kim Michelle B, Kuo Katie M, Wang Tao, Sum Chi S, Cvijic Mary E, Schroeder Gretchen M, Wilson Lawrence J, Liotta Dennis C

机构信息

Department of Chemistry, Emory University, 1515 Dickey Drive NE, Atlanta, Georgia 30322, United States.

Bristol-Myers Squibb Research & Development, Princeton, New Jersey 08543, United States.

出版信息

ACS Med Chem Lett. 2017 Dec 20;9(2):89-93. doi: 10.1021/acsmedchemlett.7b00406. eCollection 2018 Feb 8.

DOI:10.1021/acsmedchemlett.7b00406
PMID:29456793
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5807867/
Abstract

A structure-activity relationship study of potent TIQ15-derived CXCR4 antagonists is reported. In this investigation, the TIQ15 side-chain was constrained to improve its drug properties. The cyclohexylamino congener was found to be a potent CXCR4 inhibitor (IC = 33 nM in CXCL12-mediated Ca flux) with enhanced stability in liver microsomes and reduced inhibition of CYP450 (2D6). The improved CXCR4 antagonist has potential therapeutic application as a single agent or combinatory anticancer therapy.

摘要

报道了强效TIQ15衍生的CXCR4拮抗剂的构效关系研究。在本研究中，对TIQ15侧链进行了限制以改善其药物性质。发现环己基氨基类似物是一种强效的CXCR4抑制剂（在CXCL12介导的钙流中IC = 33 nM），在肝微粒体中稳定性增强，对CYP450（2D6）的抑制作用降低。改进后的CXCR4拮抗剂作为单一药物或联合抗癌疗法具有潜在的治疗应用价值。