Benzenesulfonamides: A Unique Class of Chemokine Receptor Type 4 Inhibitors. Issue 4 (6th March 2013)

• Record Type: Journal Article
• Authors: Mooring, Suazette Reid; Liu, Jin; Liang, Zhongxing; Ahn, Jeffrey; Hong, Samuel; Yoon, Younghyoun; Snyder, James P.; Shim, Hyunsuk
• Is Part Of: ChemMedChem. Volume 8:Issue 4(2013:Apr.)
• Page Start: 622
• Page End: 632
• Publication Date: 2013-03-06
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201200582
• Languages: English
• ISSNs: 1860-7179

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>The interaction of CXCR4 with CXCL12 (SDF‐1) plays a critical role in cancer metastasis by facilitating the homing of tumor cells to metastatic sites. Based on our previously published work on CXCR4 antagonists, we have synthesized a series of aryl sulfonamides that inhibit the CXCR4/CXCL12 interaction. Analogue bioactivities were assessed with binding affinity and Matrigel invasion assays. Computer modeling was employed to evaluate a selection of the new analogues docked into the CXCR4 X‐ray structure and to rationalize discrepancies between the affinity and Matrigel in vitro assays. A lead compound displays nanomolar potency in the binding affinity assay (IC₅₀=8.0 n<sc>M</sc>) and the Matrigel invasion assay (100 % blockade of invasion at 10 n<sc>M</sc>). These data demonstrate that benzenesulfonamides are a unique class of CXCR4 inhibitors with high potency.</p> </abstract>