Suppression of prostate cancer pathogenesis using an MDA-9/Syntenin (SDCBP) PDZ1 small molecule inhibitor
作者： Swadesh K Das , Timothy P Kegelman , Anjan K Pradhan , Xue-Ning Shen , Praveen Bhoopathi
DOI: 10.1158/1535-7163.MCT-18-1019
关键词:
摘要: Metastasis is the primary determinant of death in patients with diverse solid tumors and MDA-9/Syntenin (SDCBP), a pro-metastatic pro-angiogenic gene, contributes to this process. Recently, we documented that by physically interacting IGF-1R, activates STAT3 regulates prostate cancer pathogenesis. These observations firmly established as potential molecular target cancer. contains two highly homologous PDZ domains predicted interact plethora proteins, many which are central cancerous An PDZ1 domain-targeted small molecule (PDZ1i) was previously developed using fragment-based drug discovery (FBDD) guided NMR spectroscopy found be well-tolerated vivo, had significant half-life (t1/2 = 9 hours) displayed substantial anti-prostate preclinical vivo activity. PDZ1i blocked tumor cell invasion migration vitro, metastasis vivo. Hence, demonstrate an target-specific small-molecule inhibitor displays therapeutic for potentially other cancers expressing elevated levels MDA-9/Syntenin.
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