ArticleACS chemical biology2012
A novel mechanism by which small molecule inhibitors induce the DFG flip in Aurora A.
Article in ACS chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 64 citations in OpenAlex.
- Computationally guided optimization of the antimalarial activity and physicochemical properties of 2,4-diaminopyrimidines.RSC medicinal chemistry · 2025Article
- [Characteristics of Aurora Kinase A-Mediated Tumor Microenvironment in Colorectal Cancer and Mining of Active Compounds From Chinese Herbs].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- Predicting Inhibition of CDK2 with SAnDReS: The Application of Machine Learning to Navigate the Scoring Function Space.Current medicinal chemistry · 2025Review
- Evaluating the ability of end-point methods to predict the binding affinity tendency of protein kinase inhibitors.RSC advances · 2023Article
- The Essential Oil fromPharmaceuticals (Basel, Switzerland) · 2022Article
- Cytosolic localization and in vitro assembly of human de novo thymidylate synthesis complex.The FEBS journal · 2022Article
- Aurora Kinase A Is Involved in Controlling the Localization of Aquaporin-2 in Renal Principal Cells.International journal of molecular sciences · 2022Article
- PHA-680626 Is an Effective Inhibitor of the Interaction between Aurora-A and N-Myc.International journal of molecular sciences · 2021Article
- Discovery and Synthesis of a Pyrimidine-Based Aurora Kinase Inhibitor to Reduce Levels of MYC Oncoproteins.Journal of medicinal chemistry · 2021Article
- Development of a potent and selective chemical probe for the pleiotropic kinase CK2.Cell chemical biology · 2021Article
- How Far Are We from the Rapid Prediction of Drug Resistance Arising Due to Kinase Mutations?ACS omega · 2021Article
- Divergent Polypharmacology-Driven Cellular Activity of Structurally Similar Multi-Kinase Inhibitors through Cumulative Effects on Individual Targets.Cell chemical biology · 2019Article
- Application of the SwissDrugDesign Online Resources in Virtual Screening.International journal of molecular sciences · 2019Review
- Design, synthesis, and biological evaluation of polyphenols with 4,6-diphenylpyrimidin-2-amine derivatives for inhibition of Aurora kinase A.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2019Article
- Inhibitory Effect of Synthetic Flavone Derivatives on Pan-Aurora Kinases: Induction of G2/M Cell-Cycle Arrest and Apoptosis in HCT116 Human Colon Cancer Cells.International journal of molecular sciences · 2018Article
- The multifaceted allosteric regulation of Aurora kinase A.The Biochemical journal · 2018Review
- Article
- A water-mediated allosteric network governs activation of Aurora kinase A.Nature chemical biology · 2017Article
- Identification and Characterization of an Irreversible Inhibitor of CDK2.Chemistry & biology · 2015Article
- Development of novel ACK1/TNK2 inhibitors using a fragment-based approach.Journal of medicinal chemistry · 2015Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Most protein kinases share a DFG (Asp-Phe-Gly) motif in the ATP site that can assume two distinct conformations, the active DFG-in and the inactive DFG-out states. Small molecule inhibitors able to induce the DFG-out state have received considerable attention in kinase drug discovery. Using a typical DFG-in inhibitor scaffold of Aurora A, a kinase involved in the regulation of cell division, we found that halogen and nitrile substituents directed at the N-terminally flanking residue Ala273 induced global conformational changes in the enzyme, leading to DFG-out inhibitors that are among the most potent Aurora A inhibitors reported to date. The data suggest an unprecedented mechanism of action, in which induced-dipole forces along the Ala273 side chain alter the charge distribution of the DFG backbone, allowing the DFG to unwind. As the ADFG sequence and three-dimensional structure is highly conserved, DFG-out inhibitors of other kinases may be designed by specifically targeting the flanking alanine residue with electric dipoles.
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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.