Design, synthesis and prostate cancer cell-based studies of analogs of the Rho/MKL1 transcriptional pathway inhibitor, CCG-1423
| Autor: | Scott D. Larsen, Susan M. Wade, Andrew J. Kocab, Nicole L. Harzdorf, Jessica L. Bell, H. D. Hollis Showalter, Richard R. Neubig, Jenny G. Ryu, Chris R. Evelyn |
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| Rok vydání: | 2009 |
| Předmět: |
Male
RHOA Oncogene Proteins Fusion Transcription Genetic Clinical Biochemistry Response element Pharmaceutical Science Biochemistry Article Prostate cancer Structure-Activity Relationship Blood serum Piperidines Cell Line Tumor Drug Discovery Serum response factor medicine Humans Anilides Neoplasm Invasiveness Enzyme Inhibitors Cytotoxicity Molecular Biology Matrigel Aniline Compounds biology Chemistry Organic Chemistry Prostatic Neoplasms medicine.disease DNA-Binding Proteins Cell culture Drug Design Benzamides biology.protein Cancer research Trans-Activators Molecular Medicine rhoA GTP-Binding Protein |
| Zdroj: | Bioorganicmedicinal chemistry letters. 20(2) |
| ISSN: | 1464-3405 |
| Popis: | We recently identified bis(amide) CCG-1423 (1) as a novel inhibitor of RhoA/C-mediated gene transcription that is capable of inhibiting invasion of PC-3 prostate cancer cells in a Matrigel model of metastasis. An initial structure-activity relationship study focusing on bioisosteric replacement of the amides and conformational restriction identified two compounds, 4g and 8, with improved selectivity for inhibition of RhoA/C-mediated gene transcription and attenuated cytotoxicity relative to 1. Both compounds were also capable of inhibiting cell invasion with equal efficacy to 1 but with less attendant cytotoxicity. |
| Databáze: | OpenAIRE |
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