Benzenesulfonamides: A Unique Class of Chemokine Receptor Type 4 Inhibitors

• DOI: 10.1002/cmdc.201200582
• Publication Date: 2013-03-06T17:57:52Z
• Authors: Suazette Reid Moo...; Jin Liu; Zhongxing Liang; Jeffrey Ahn; Samuel Hong; Younghyoun Yoon; James P. Snyder; Hyunsuk Shim
• Keywords: Matrigel; Ligand binding assay

Abstract The interaction of CXCR4 with CXCL12 (SDF‐1) plays a critical role in cancer metastasis by facilitating the homing tumor cells to metastatic sites. Based on our previously published work antagonists, we have synthesized series aryl sulfonamides that inhibit CXCR4/CXCL12 interaction. Analogue bioactivities were assessed binding affinity and Matrigel invasion assays. Computer modeling was employed evaluate selection new analogues docked into X‐ray structure rationalize discrepancies between vitro A lead compound displays nanomolar potency assay (IC 50 =8.0 n M ) (100 % blockade at 10 ). These data demonstrate benzenesulfonamides are unique class inhibitors high potency.