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The initial structure activity relationships around an isoindoline uHTS hit will be described. Information gleaned from ligand co-crystal structures allowed for rapid refinements in both MARK potency and kinase selectivity. These efforts allowed for the identification of a compound with properties suitable for use as an in vitro tool compound for validation studies on MARK as a viable target for Alzheimer's disease.
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http://dx.doi.org/10.1016/j.bmcl.2016.08.068 | DOI Listing |
NIHR Open Res
September 2025
Department of Neurology, North Bristol NHS Trust, Westbury on Trym, England, UK.
Background: This study aimed to explore the barriers and facilitators of implementing rehabilitation interventions for visual field loss due to stroke.
Methods: The study was a qualitative exploration using one-to-one interviews coded using template analysis and the COM-B a-priori framework. Participants were five occupational therapists from hospital (n=4) and community (n=1) National Health Service (NHS) stroke care settings in England.
J Am Chem Soc
September 2025
Kekulé Institute for Organic Chemistry and Biochemistry, University of Bonn,Gerhard-Domagk-Straße 1,Bonn 53121,Germany.
Terpene synthases produce a remarkable structural diversity from acyclic precursors through complex carbocation cascades. Here, we report the crystal structure of the bacterial sesterterpene synthase StvirS bound to geranylfarnesyl thiopyrophosphate (GFSPP), revealing a preorganized active site that enforces a defined folding of the C25 backbone. Guided by this structure, active-site engineering at 11 positions yielded 23 enzyme variants and 13 new sesterterpenes.
View Article and Find Full Text PDFMol Inform
September 2025
Department of Computational Chemistry, "Coriolan Drăgulescu" Institute of Chemistry Timișoara, Romanian Academy, Timișoara, Romania.
Docking is a structure-based cheminformatics tool broadly employed in early drug discovery. Based on the tridimensional structure of the protein target, docking is used to predict the binding interactions between the protein and a ligand, estimate the corresponding binding affinity, or perform virtual screenings (VSs) to identify new active compounds. This study introduces the ligand B-factor index (LBI), a novel computational metric for prioritizing protein-ligand complexes for docking.
View Article and Find Full Text PDFInt J Cosmet Sci
September 2025
LVMH Recherche, CEECI, Neuilly-sur-Seine, France.
In the human face, the lips play a key role in social interactions and are a major element of makeup strategies. However, the amount of data available on lips, particularly relating to colour, is limited in comparison to that on skin. To gain a better understanding of lip colour, this study aimed to assess its diversity across four ethnicities (Asian Chinese, African American, Hispanic American and Caucasian American and French).
View Article and Find Full Text PDFNat Commun
September 2025
Institute of Computational Biology, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany.
Atherosclerosis, a major cause of cardiovascular diseases, is characterized by the buildup of lipids and chronic inflammation in the arteries, leading to plaque formation and potential rupture. Despite recent advances in single-cell transcriptomics (scRNA-seq), the underlying immune mechanisms and transformations in structural cells driving plaque progression remain incompletely defined. Existing datasets often lack comprehensive coverage and consistent annotations, limiting the utility of downstream analyses.
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