ArticleACS medicinal chemistry letters2019
Discovering New Casein Kinase 1d Inhibitors with an Innovative Molecular Dynamics Enabled Virtual Screening Workflow.
Article in ACS medicinal chemistry letters, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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Who cites it
4 citing papers in PubMed.
- Structure-Based Optimization of Selective and Brain Penetrant CK1δ Inhibitors for the Treatment of Circadian Disruptions.ACS medicinal chemistry letters · 2024Article
- Structural Investigations on 2-Amidobenzimidazole Derivatives as New Inhibitors of Protein Kinase CK1 Delta.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Chemical Modulation of the 1-(Piperidin-4-yl)-1,3-dihydro-2Molecules (Basel, Switzerland) · 2021Article
- Use of Phenotypically Poor Metabolizer Individual Donor Human Liver Microsomes To Identify Selective Substrates of UGT2B10.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The value of including protein flexibility in structure-based drug design (SBDD) is widely documented, and currently, molecular dynamics (MD) simulations represent a powerful tool to investigate protein dynamics. Yet, the inclusion of MD-derived information in pre-existing SBDD workflows is still far from trivial. We recently published an integrated MD-FLAP (Fingerprints for Ligands and Proteins) approach combining MD, clustering and Linear Discriminant Analysis (LDA) for enhancing accuracy, efficacy, and for protein conformational selection in virtual screening (VS) campaigns. Here we prospectively applied the MD-FLAP workflow to discover novel chemotypes inhibiting the Casein Kinase 1 delta (CSNK1D) enzyme. We first obtained a VS model able to separate active from inactive compounds, with a global AUC of 0.9 and a partial ROC enrichment at 0.5% of 0.18, and use it to mine the internal Pfizer screening database. Seven active molecules sharing a phenyl-indazole scaffold, not yet reported among CSNK1D inhibitors, were found. The most potent inhibitor showed an IC
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Registered trials
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