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Updated: Jan 21, 2026

Isolation of Cancer Stem Cells From Human Prostate Cancer Samples
Published on: March 14, 2014
Suppression of Prostate Cancer Pathogenesis Using an MDA-9/Syntenin (SDCBP) PDZ1 Small-Molecule Inhibitor
Swadesh K Das1,2,3, Timothy P Kegelman4, Anjan K Pradhan4
1Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia. paul.fisher@vcuhealth.org swadesh.das@vcuhealth.org.
Abstract:
Metastasis is the primary determinant of death in patients with diverse solid tumors and MDA-9/Syntenin (SDCBP), a pro-metastatic and pro-angiogenic gene, contributes to this process. Recently, we documented that by physically interacting with IGF-1R, MDA-9/Syntenin activates STAT3 and regulates prostate cancer pathogenesis. These observations firmly established MDA-9/Syntenin as a potential molecular target in prostate cancer. MDA-9/Syntenin contains two highly homologous PDZ domains predicted to interact with a plethora of proteins, many of which are central to the cancerous process. An MDA-9/Syntenin PDZ1 domain-targeted small molecule (PDZ1i) was previously developed using fragment-based drug discovery (FBDD) guided by NMR spectroscopy and was found to be well-tolerated in vivo, had significant half-life (t 1/2 = 9 hours) and displayed substantial anti-prostate cancer preclinical in vivo activity. PDZ1i blocked tumor cell invasion and migration in vitro, and metastasis in vivo Hence, we demonstrate that PDZ1i an MDA-9/Syntenin PDZ1 target-specific small-molecule inhibitor displays therapeutic potential for prostate and potentially other cancers expressing elevated levels of MDA-9/Syntenin.
Insights
A novel small molecule inhibitor targeting MDA-9/Syntenin (SDCBP) shows promise for treating prostate cancer. This inhibitor effectively blocked tumor cell invasion and migration, suggesting therapeutic potential for various cancers.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Metastasis is a leading cause of cancer-related death in solid tumors.
- MDA-9/Syntenin (SDCBP) is a pro-metastatic and pro-angiogenic gene implicated in prostate cancer pathogenesis.
- MDA-9/Syntenin interacts with IGF-1R, activating STAT3 and regulating cancer progression.
Purpose of the Study:
- To evaluate the therapeutic potential of a small molecule inhibitor targeting the PDZ1 domain of MDA-9/Syntenin (PDZ1i).
- To assess the efficacy of PDZ1i in preclinical models of prostate cancer.
Main Methods:
- Development of PDZ1i using fragment-based drug discovery (FBDD) guided by NMR spectroscopy.
- In vitro and in vivo studies to evaluate the anti-cancer activity of PDZ1i.
- Assessment of tumor cell invasion, migration, and metastasis.
Main Results:
- PDZ1i demonstrated good in vivo tolerability and a half-life of 9 hours.
- PDZ1i exhibited significant preclinical anti-prostate cancer activity in vivo.
- PDZ1i effectively inhibited tumor cell invasion and migration in vitro and metastasis in vivo.
Conclusions:
- PDZ1i is a specific small-molecule inhibitor of the MDA-9/Syntenin PDZ1 domain.
- PDZ1i displays therapeutic potential for prostate cancer and potentially other cancers with elevated MDA-9/Syntenin levels.
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