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Benzenesulfonamides: A Unique Class of Chemokine Receptor Type 4 Inhibitors
Author(s) -
Mooring Suazette Reid,
Liu Jin,
Liang Zhongxing,
Ahn Jeffrey,
Hong Samuel,
Yoon Younghyoun,
Snyder James P.,
Shim Hyunsuk
Publication year - 2013
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201200582
Subject(s) - matrigel , cxcr4 , potency , in vitro , chemokine receptor , chemistry , ligand binding assay , receptor , cancer research , chemokine , biochemistry , biology , pharmacology
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 (IC 50 =8.0 n M ) and the Matrigel invasion assay (100 % blockade of invasion at 10 n M ). These data demonstrate that benzenesulfonamides are a unique class of CXCR4 inhibitors with high potency.