1,928 results found
    1. Human biology and medicine

    Point of View: Why clinical translation cannot succeed without failure

    Alex John London, Jonathan Kimmelman
    The high rates of attrition that occur in drug development are widely regarded as problematic, but the failure of well-designed studies benefits both researchers and healthcare systems.
    1. Cancer Biology

    BRET-based RAS biosensors that show a novel small molecule is an inhibitor of RAS-effector protein-protein interactions

    Nicolas Bery et al.
    A biosensor resource has been developed to monitor the intracellular interactions of RAS family proteins with effector molecules and the effects of inhibitors as an aid to drug development.
    1. Developmental Biology
    2. Neuroscience

    Cis and trans RET signaling control the survival and central projection growth of rapidly adapting mechanoreceptors

    Michael S Fleming et al.
    Cis and trans activation of the receptor tyrosine kinase RET lead to similar biological outcomes in rapidly adapting mechanoreceptors in vivo.
    1. Cancer Biology
    2. Cell Biology

    The anticancer natural product ophiobolin A induces cytotoxicity by covalent modification of phosphatidylethanolamine

    Christopher Chidley et al.
    An unbiased genetic screen in human cells shows that the molecular target of a natural product with promising anticancer activity is a membrane phospholipid.
    1. Structural Biology and Molecular Biophysics

    Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine

    Wilson Wong et al.
    The molecular mechanism behind how emetine inhibits the ribosome of the human malaria parasite, along with structural details of the complex formed, is revealed at high resolution using cryo-electron microscopy.
    1. Biochemistry and Chemical Biology
    2. Developmental Biology

    Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome

    Katherine A Donovan et al.
    Thalidomide and its derivates induce degradation of many C2H2 zinc-finger transcription factors, including SALL4, providing insight into a long-standing mystery in modern pharmacology, and starting points for future drug development.
    1. Cancer Biology
    2. Cell Biology

    Bim escapes displacement by BH3-mimetic anti-cancer drugs by double-bolt locking both Bcl-XL and Bcl-2

    Qian Liu et al.
    The pro-apoptotic BH3-protein Bim contains two distinct binding sites for anti-apoptotic proteins that together confer resistance of Bim/Bcl-2 and Bim/Bcl-XL complexes to BH3-mimetic drugs under development for use in humans.
    1. Human Biology and Medicine
    2. Neuroscience

    Mouse models of human PIK3CA-related brain overgrowth have acutely treatable epilepsy

    Achira Roy et al.
    Acute one-hour treatment of Pik3ca mutant mice with a novel anti-epilepsy drug suppresses seizures despite continued developmental brain dysmorphology, promising a new therapeutic strategy for patients with intractable pediatric epilepsy.
    1. Human Biology and Medicine
    2. Stem Cells and Regenerative Medicine

    Merging organoid and organ-on-a-chip technology to generate complex multi-layer tissue models in a human retina-on-a-chip platform

    Kevin Achberger et al.
    A microphysiological system (retina-on-a-chip) shows the potential to promote drug development and provide new insights into the underlying pathology of retinal diseases.
    1. Cancer Biology
    2. Human Biology and Medicine

    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.

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