ArticleChemMedChem2019
Discovery of CDK8/CycC Ligands with a New Virtual Screening Tool.
Article in ChemMedChem, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Computation of Protein-Ligand Binding Free Energies with a Quantum Mechanics-Based Mining Minima Algorithm.Journal of chemical theory and computation · 2025Article
- Uncovering water effects in protein-ligand recognition: importance in the second hydration shell and binding kinetics.Physical chemistry chemical physics : PCCP · 2023Article
- Capture of activated dioxygen intermediates at the copper-active site of a lytic polysaccharide monooxygenase.Chemical science · 2022Article
- Computation of host-guest binding free energies with a new quantum mechanics based mining minima algorithm.The Journal of chemical physics · 2021Article
- Pyrazolyl-Ureas as Interesting Scaffold in Medicinal Chemistry.Molecules (Basel, Switzerland) · 2020Review
- Transient States and Barriers from Molecular Simulations and the Milestoning Theory: Kinetics in Ligand-Protein Recognition and Compound Design.Journal of chemical theory and computation · 2020Article
- Article
- Super-Enhancers in the Regulation of Gene Transcription: General Aspects and Antitumor Targets.Acta naturaeArticle
Corrections and comments
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Authors and funding
3 authors at 1 institution in 3 countries.
Funding
Abstract
Selective inhibition of cyclin-dependent kinase 8 and cyclin C (CDK8/CycC) has been suggested as a promising strategy for decreasing mitogenic signals in cancer cells with reduced toxicity toward normal cells. We developed a novel virtual screening protocol for drug development and applied it to the discovery of new CDK8/CycC type II ligands, which is likely to achieve long residence time and specificity. We first analyzed the binding thermodynamics of 11 published pyrazolourea ligands using molecular dynamics simulations and a free-energy calculation method, VM2, and extracted the key binding information to assist virtual screening. The urea moiety was found to be the critical structural contributor of the reference ligands. Starting with the urea moiety, we conducted substructure-based searches with our newly developed superposition and single-point energy evaluation method, followed by free-energy calculations, and singled out three purchasable compounds for bioassay testing. The ranking from the experimental results is completely consistent with the predicted rankings. A potent drug-like compound was found to have a K
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.