1,840 results found
    1. Cancer Biology

    Assessing the mechanism and therapeutic potential of modulators of the human Mediator complex-associated protein kinases

    Paul A Clarke et al.
    Detailed molecular profiling investigations alongside antitumor testing and tolerability studies in animals suggest caution when considering the clinical development of inhibitors of CDK8 and CDK19, since a clear therapeutic window could not be demonstrated with two structurally distinct, potent and selective prototype drugs.
    1. Cancer Biology

    Development of Bag-1L as a therapeutic target in androgen receptor-dependent prostate cancer

    Laura Cato et al.
    Targeting the activation of the androgen receptor N-terminal domain by the cochaperone Bag-1L provides a new approach for inhibiting androgen receptor function to treat prostate cancer.
    1. Cancer Biology

    Marked synergy by vertical inhibition of EGFR signaling in NSCLC spheroids shows SOS1 is a therapeutic target in EGFR-mutated cancer

    Patricia L Theard et al.
    Combined EGFR and SOS1 inhibition synergize to inhibit NSCLC spheroid growth.
    1. Neuroscience

    SARM1 depletion rescues NMNAT1-dependent photoreceptor cell death and retinal degeneration

    Yo Sasaki et al.
    A mouse model of retinal degeneration reveals a common mechanism for axonal degeneration and photoreceptor cell death and identifies SARM1 as a therapeutic candidate for retinopathies.
    1. Cancer Biology
    2. Medicine

    Science Forum: Challenges in validating candidate therapeutic targets in cancer

    Jeffrey Settleman et al.
    More than 30 published articles have suggested that a protein kinase called MELK is an attractive therapeutic target in human cancer, but three recent reports describe compelling evidence that it is not.
    1. Cancer Biology

    A comprehensive analysis of coregulator recruitment, androgen receptor function and gene expression in prostate cancer

    Song Liu et al.
    Coregulators mediate selective interactions between DNA-bound androgen receptor and other transcription factors, which control distinct prostate cancer biology, suggesting disruption of critical interactions in these complexes as a novel therapeutic strategy.
    1. Cell Biology
    2. Developmental Biology

    Activation of PTHrP-cAMP-CREB1 signaling following p53 loss is essential for osteosarcoma initiation and maintenance

    Mannu K Walia et al.
    The loss of p53 in bone cells activates critical signaling pathways; these are also essential in bone cancer.
    1. Cancer Biology

    Functional interrogation of HOXA9 regulome in MLLr leukemia via reporter-based CRISPR/Cas9 screen

    Hao Zhang et al.
    The HOXA9 reporter and genetic screens facilitated the functional interrogation of the HOXA9 regulome and advanced our understanding of the molecular regulation network in HOXA9-driven leukemia.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Small molecule proteostasis regulators that reprogram the ER to reduce extracellular protein aggregation

    Lars Plate et al.
    Small molecule proteostasis regulators that activate the unfolded protein response transcription factor ATF6 reduce the secretion of amyloid disease-associated proteins.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    Small-molecule inhibitors identify the RAD52-ssDNA interaction as critical for recovery from replication stress and for survival of BRCA2 deficient cells

    Sarah R Hengel et al.
    Small molecule inhibitors identified in a biophysical high-throughout screening assay confirm the importance of the interaction between single-stranded DNA and the protein RAD52 for the survival of BRCA2-depleted cells.

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