ArticleACS pharmacology & translational science2023
Rigid Scaffolds Are Promising for Designing Macrocyclic Kinase Inhibitors.
Article in ACS pharmacology & translational science, 2023. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed.
- Exploring Extended Warheads toward Developing Cysteine-Targeted Covalent Kinase Inhibitors.Journal of chemical information and modeling · 2024Article
- Exploring SureChEMBL from a drug discovery perspective.Scientific data · 2024Article
- Structure-Based Optimization of Pyrazinamide-Containing Macrocyclic Derivatives as Fms-like Tyrosine Kinase 3 (FLT3) Inhibitors to Overcome Clinical Mutations.ACS pharmacology & translational science · 2024Article
- Review
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrocyclic kinase inhibitors (MKIs) are gaining attention due to their favorable selectivity and potential to overcome drug resistance, yet they remain challenging to design because of their novel structures. To facilitate the design and discovery of MKIs, we investigate MKI rational design starting from initial acyclic compounds by performing microsecond-scale atomistic simulations for multiple MKIs, constructing an MKI database, and analyzing MKIs using hierarchical cluster analysis. Our studies demonstrate that the binding modes of MKIs are like those of their corresponding acyclic counterparts against the same kinase targets. Importantly, within the respective binding sites, the MKI scaffolds retain the same conformations as their corresponding acyclic counterparts, demonstrating the rigidity of scaffolds before and after molecular cyclization. The MKI database includes 641 nanomole-level MKIs from 56 human kinases elucidating the features of rigid scaffolds and the core structures of MKIs. Collectively these results and resources can facilitate MKI development.
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Registered trials
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