1431950-16-1Relevant articles and documents
Benzenesulfonamides: A Unique Class of Chemokine Receptor Type4 Inhibitors
Mooring, Suazette Reid,Liu, Jin,Liang, Zhongxing,Ahn, Jeffrey,Hong, Samuel,Yoon, Younghyoun,Snyder, James P.,Shim, Hyunsuk
, p. 622 - 632 (2013/08/22)
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 invitro assays. A lead compound displays nanomolar potency in the binding affinity assay (IC50=8.0nM) and the Matrigel invasion assay (100% blockade of invasion at 10nM). These data demonstrate that benzenesulfonamides are a unique class of CXCR4 inhibitors with high potency.