ccg-1423 and Prostatic-Neoplasms

ccg-1423 has been researched along with Prostatic-Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for ccg-1423 and Prostatic-Neoplasms

ArticleYear
Optimization of novel nipecotic bis(amide) inhibitors of the Rho/MKL1/SRF transcriptional pathway as potential anti-metastasis agents.
    Bioorganic & medicinal chemistry letters, 2013, Jul-01, Volume: 23, Issue:13

    CCG-1423 (1) is a novel inhibitor of Rho/MKL1/SRF-mediated gene transcription that inhibits invasion of PC-3 prostate cancer cells in a Matrigel model of metastasis. We recently reported the design and synthesis of conformationally restricted analogs (e.g., 2) with improved selectivity for inhibiting invasion versus acute cytotoxicity. In this study we conducted a survey of aromatic substitution with the goal of improving physicochemical parameters (e.g., ClogP, MW) for future efficacy studies in vivo. Two new compounds were identified that attenuated cytotoxicity even further, and were fourfold more potent than 2 at inhibiting PC-3 cell migration in a scratch wound assay. One of these (8a, CCG-203971, IC50=4.2 μM) was well tolerated in mice for 5 days at 100mg/kg/day i.p., and was able to achieve plasma levels exceeding the migration IC50 for up to 3 h.

    Topics: Amides; Anilides; Antineoplastic Agents; Benzamides; Cell Line, Tumor; Cell Movement; Cell Proliferation; DNA-Binding Proteins; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Male; Molecular Structure; Neoplasm Metastasis; Nipecotic Acids; Oncogene Proteins, Fusion; Prostatic Neoplasms; rhoA GTP-Binding Protein; Serum Response Factor; Structure-Activity Relationship; Trans-Activators

2013
Design, synthesis and prostate cancer cell-based studies of analogs of the Rho/MKL1 transcriptional pathway inhibitor, CCG-1423.
    Bioorganic & medicinal chemistry letters, 2010, Jan-15, Volume: 20, Issue:2

    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.

    Topics: Anilides; Aniline Compounds; Benzamides; Cell Line, Tumor; DNA-Binding Proteins; Drug Design; Enzyme Inhibitors; Humans; Male; Neoplasm Invasiveness; Oncogene Proteins, Fusion; Piperidines; Prostatic Neoplasms; rhoA GTP-Binding Protein; Structure-Activity Relationship; Trans-Activators; Transcription, Genetic

2010