1,531 results found
    1. Biochemistry and Chemical Biology

    Assessing target engagement using proteome-wide solvent shift assays

    Jonathan G Van Vranken, Jiaming Li ... Steven P Gygi
    Solvent shift assays such as solvent proteome profiling and solvent-PISA are valuable tools for identifying protein-ligand interactions on a proteome-wide scale and can be used to determine drug target engagement, which should benefit future drug discovery efforts.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response

    Carmela Sidrauski, Jordan C Tsai ... Peter Walter
    A drug-like molecule called ISRIB, which activates the translation initiation factor eIF2B, antagonizes stress responses as diverse as protein misfolding and nutrient deprivation, and restores protein synthesis, enhancing memory.
    1. Biochemistry and Chemical Biology

    Impact of protein and small molecule interactions on kinase conformations

    Valentina Kugler, Selina Schwaighofer ... Eduard Stefan
    Kinase conformation reporters reveal how protein kinase activity conformations are influenced by regulatory protein interactions, patient mutations, and cellular drug binding, aiding in systematically anticipating treatment efficacy and designing patient-tailored therapies.
    1. Neuroscience

    Dynamics and maintenance of categorical responses in primary auditory cortex during task engagement

    Rupesh K Chillale, Shihab Shamma ... Yves Boubenec
    Primary auditory cortex shows population-level correlates of sound categorization, with categorical patterns emerging during sound presentation and task engagement leading to asymmetrical representation of stimuli, indicating an early involvement in stimulus categorization.
    1. Developmental Biology

    A β-catenin-driven switch in TCF/LEF transcription factor binding to DNA target sites promotes commitment of mammalian nephron progenitor cells

    Qiuyu Guo, Albert Kim ... Andrew P McMahon
    β-Catenin-mediated expansion of nephron progenitors is independent of direct β-catenin/chromatin engagement, while progenitor induction proceeds with a β-catenin-driven switch of repressive TCFL1/TCFL2 to activating TCF7/LEF1 factors on transcriptionally poised enhancers.
    1. Computational and Systems Biology

    Population dynamics of immunological synapse formation induced by bispecific T cell engagers predict clinical pharmacodynamics and treatment resistance

    Can Liu, Jiawei Zhou ... Yanguang Cao
    Modeling the dynamics of immunological synapses informs pharmacodynamics and treatment resistance to bispecific T cell engagers.
    1. Biochemistry and Chemical Biology
    2. Cancer Biology

    Destabilizers of the thymidylate synthase homodimer accelerate its proteasomal degradation and inhibit cancer growth

    Luca Costantino, Stefania Ferrari ... Maria Paola Costi
    The dimer destabilizers cause a dimer-to-monomer equilibrium shift favoring the human thymidylate synthase monomer more degradable by the proteasome, thus breaking the long-standing link between inhibition and enhanced expression of the protein to fight cancer drug resistance.
    1. Biochemistry and Chemical Biology

    Large-scale characterization of drug mechanism of action using proteome-wide thermal shift assays

    Jonathan G Van Vranken, Jiaming Li ... Devin K Schweppe
    An approachable framework for the scalable implementation of proteome-wide thermal shift assays to assess drug mechanisms of action.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Hypothemycin, a fungal natural product, identifies therapeutic targets in Trypanosoma brucei

    Mari Nishino, Jonathan W Choy ... Jack Taunton
    Hypothemycin, which inhibits a number of protein kinases, kills the T. brucei parasites that cause sleeping sickness and reveals new therapeutic targets for the disorder.
    1. Neuroscience

    Behavioural and neural signatures of perceptual decision-making are modulated by pupil-linked arousal

    Jochem van Kempen, Gerard M Loughnane ... Mark A Bellgrove
    A direct relationship between pupil diameter and electrophysiological correlates of attention, sensory stimulus processing and target detection was observed demonstrating that arousal has a substantial influence on perceptual decision-making.

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