ArticleJournal of medicinal chemistry2013
How to deal with low-resolution target structures: using SAR, ensemble docking, hydropathic analysis, and 3D-QSAR to definitively map the αβ-tubulin colchicine site.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 38 citations in OpenAlex.
- Web-Based Quantitative Structure-Activity Relationship Resources Facilitate Effective Drug Discovery.Topics in current chemistry (Cham) · 2021Review
- 3D Interaction Homology: Computational Titration of Aspartic Acid, Glutamic Acid and Histidine Can Create pH-Tunable Hydropathic Environment Maps.Frontiers in molecular biosciences · 2021Article
- Targeting the C-Terminal Domain Small Phosphatase 1.Life (Basel, Switzerland) · 2020Review
- Structure-Activity Relationship Studies of β-Lactam-azide Analogues as Orally Active Antitumor Agents Targeting the Tubulin Colchicine Site.Scientific reports · 2017Article
- The Development of Target-Specific Pose Filter Ensembles To Boost Ligand Enrichment for Structure-Based Virtual Screening.Journal of chemical information and modeling · 2017Article
- Ortho group activation of a bromopyrrole ester in Suzuki-Miyaura cross-coupling reactions: Application to the synthesis of new microtubule depolymerizing agents with potent cytotoxic activities.Bioorganic & medicinal chemistry · 2017Article
- Biological Characterization of an Improved Pyrrole-Based Colchicine Site Agent Identified through Structure-Based Design.Molecular pharmacology · 2016Article
- Profiling the interaction mechanism of quinoline/quinazoline derivatives as MCHR1 antagonists: an in silico method.International journal of molecular sciences · 2014Article
- The design and discovery of water soluble 4-substituted-2,6-dimethylfuro[2,3-d]pyrimidines as multitargeted receptor tyrosine kinase inhibitors and microtubule targeting antitumor agents.Bioorganic & medicinal chemistry · 2014Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
αβ-Tubulin colchicine site inhibitors (CSIs) from four scaffolds that we previously tested for antiproliferative activity were modeled to better understand their effect on microtubules. Docking models, constructed by exploiting the SAR of a pyrrole subset and HINT scoring, guided ensemble docking of all 59 compounds. This conformation set and two variants having progressively less structure knowledge were subjected to CoMFA, CoMFA+HINT, and CoMSIA 3D-QSAR analyses. The CoMFA+HINT model (docked alignment) showed the best statistics: leave-one-out q(2) of 0.616, r(2) of 0.949, and r(2)pred (internal test set) of 0.755. An external (tested in other laboratories) collection of 24 CSIs from eight scaffolds were evaluated with the 3D-QSAR models, which correctly ranked their activity trends in 7/8 scaffolds for CoMFA+HINT (8/8 for CoMFA). The combination of SAR, ensemble docking, hydropathic analysis, and 3D-QSAR provides an atomic-scale colchicine site model more consistent with a target structure resolution much higher than the ~3.6 Å available for αβ-tubulin.
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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.