sgi-1776 and Prostatic-Neoplasms

sgi-1776 has been researched along with Prostatic-Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for sgi-1776 and Prostatic-Neoplasms

ArticleYear
Synthesis and biological evaluation of quinoline derivatives as potential anti-prostate cancer agents and Pim-1 kinase inhibitors.
    Bioorganic & medicinal chemistry, 2016, Apr-15, Volume: 24, Issue:8

    In this work, a series of quinoline derivatives were designed and synthesized as antitumor agents. Most quinolines showed potent anti-proliferative activity against human prostatic cancer PC-3 cell line. Among which, 9d, 9f and 9g were the most effective compounds with GI50 values of 2.60, 2.81 and 1.29 μM, respectively. Structure-activity relationship analysis indicated that the secondary amine linked quinoline and pyridine ring played an important role in the anti-proliferative effects. Mechanistic studies revealed that 9g was a potential Pim-1 kinase inhibitor with abilities of cell cycle arrest and apoptosis induction. Considering of the increased activity of Pim-1 in prostate cancer, such compounds have potential to be developed as anti-prostate cancer agents.

    Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Male; Molecular Structure; Prostatic Neoplasms; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-pim-1; Quinolines; Structure-Activity Relationship

2016
PIM kinase isoform specific regulation of MIG6 expression and EGFR signaling in prostate cancer cells.
    Oncotarget, 2011, Volume: 2, Issue:12

    The PIM family of oncogenic serine/threonine kinases regulates tumour cell proliferation. To identify proliferative signaling pathways that are regulated by PIM kinases we analyzed gene expression differences in DU-145 and PC3 prostate cancer derived cells induced by treatment with the recently developed highly selective PIM kinase inhibitor M-110. This identified 97 genes the expression of which is affected by M-110 in both cell lines. We then focused on the M-110 induced up regulation of the MIG6 gene that encodes a negative regulator of EGFR signaling. Here we show that M-110 and the structurally unrelated PIM kinase inhibitor SGI-1776 up regulate MIG6 in DU-145 and PC3 cells. Knockdown of PIM-1 but not of PIM-2 or PIM-3 also up regulates MIG6 expression, which identifies MIG6 as a PIM-1 regulated gene. In agreement with the role of MIG6 protein as a negative regulator of EGFR signaling we found that M-110 treatment inhibits EGF induced EGFR activation and the activation of the downstream ERK MAPkinase pathway. The biological significance of these findings are demonstrated by the fact that co-treatment of DU-145 or PC3 cells with the EGFR tyrosine kinase inhibitor Gefitinib and M-110 or SGI-1776 has synergistic inhibitory effects on cell proliferation. These experiments define a novel biological function of PIM-1 as a co-regulator of EGFR signaling and suggest that PIM inhibitors may be used in combination therapies to increase the efficacy of EGFR tyrosine kinase inhibitors.

    Topics: Adaptor Proteins, Signal Transducing; Cell Line, Tumor; Cell Proliferation; ErbB Receptors; Extracellular Signal-Regulated MAP Kinases; Gefitinib; Gene Expression Regulation, Neoplastic; Humans; Imidazoles; Male; MAP Kinase Signaling System; Prostatic Neoplasms; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-pim-1; Pyridazines; Quinazolines; RNA Interference; RNA, Small Interfering; Tumor Suppressor Proteins

2011