ArticleActa crystallographica. Section D, Biological crystallography2012
The structure of the ternary Eg5-ADP-ispinesib complex.
Article in Acta crystallographica. Section D, Biological crystallography, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 50 citations in OpenAlex.
- Molecular docking and molecular dynamics investigation of novels thiazolopyrimidines binding to canonical and alternative allosteric sites of kinesin Eg5.Journal of molecular modeling · 2026Article
- Investigation of the role of microtubule on the activity of the mitotic kinesin EG5 using multiscale modelling: unravelling molecular mechanisms.Journal of computer-aided molecular design · 2025Article
- Mitotic Functions and Characters of KIF11 in Cancers.Biomolecules · 2024Review
- MD simulation-based screening approach identified tolvaptan as a potential inhibitor of Eg5.Molecular diversity · 2023Article
- Drug resistance dependent on allostery: A P-loop rigor Eg5 mutant exhibits resistance to allosteric inhibition by STLC.Frontiers in oncology · 2022Article
- Inhibitor library screening identifies ispinesib as a new potential chemotherapeutic agent for pancreatic cancers.Cancer science · 2021Article
- enAsCas12a Enables CRISPR-Directed Evolution to Screen for Functional Drug Resistance Mutations in Sequences Inaccessible to SpCas9.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Metal-Dependent Cytotoxic and Kinesin Spindle Protein Inhibitory Activity of Ru, Os, Rh, and Ir Half-Sandwich Complexes of Ispinesib-Derived Ligands.Inorganic chemistry · 2020Article
- Predicting protein-ligand interactions based on bow-pharmacological space and Bayesian additive regression trees.Scientific reports · 2019Article
- Insights into the Molecular Mechanisms of Eg5 Inhibition by (+)-Morelloflavone.Pharmaceuticals (Basel, Switzerland) · 2019Article
- Structural and Thermodynamic Basis of the Enhanced Interaction between Kinesin Spindle Protein Eg5 and STLC-type Inhibitors.ACS omega · 2018Article
- Cancer drug therapy and stochastic modeling of "nano-motors".International journal of nanomedicine · 2018Article
- Structural basis of small molecule ATPase inhibition of a human mitotic kinesin motor protein.Scientific reports · 2017Article
- Novel Allosteric Pathway of Eg5 Regulation Identified through Multivariate Statistical Analysis of Hydrogen-Exchange Mass Spectrometry (HX-MS) Ligand Screening Data.Molecular & cellular proteomics : MCP · 2017Article
- The Kinesin-5 Chemomechanical Cycle Is Dominated by a Two-heads-bound State.The Journal of biological chemistry · 2016Article
- Recent findings and future directions for interpolar mitotic kinesin inhibitors in cancer therapy.Future medicinal chemistry · 2016Review
- Kinesin Motor Enzymology: Chemistry, Structure, and Physics of Nanoscale Molecular Machines.Biophysical reviews · 2015Article
- Niche-Based Screening in Multiple Myeloma Identifies a Kinesin-5 Inhibitor with Improved Selectivity over Hematopoietic Progenitors.Cell reports · 2015Article
- Kinesin-5 allosteric inhibitors uncouple the dynamics of nucleotide, microtubule, and neck-linker binding sites.Biophysical journal · 2014Article
- Eg5 inhibitor, a novel potent targeted therapy, induces cell apoptosis in renal cell carcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The human kinesin Eg5 is responsible for bipolar spindle formation during early mitosis. Inhibition of Eg5 triggers the formation of monoastral spindles, leading to mitotic arrest that eventually causes apoptosis. There is increasing evidence that Eg5 constitutes a potential drug target for the development of cancer chemotherapeutics. The most advanced Eg5-targeting agent is ispinesib, which exhibits potent antitumour activity and is currently in multiple phase II clinical trials. In this study, the crystal structure of the Eg5 motor domain in complex with ispinesib, supported by kinetic and thermodynamic binding data, is reported. Ispinesib occupies the same induced-fit pocket in Eg5 as other allosteric inhibitors, making extensive hydrophobic interactions with the protein. The data for the Eg5-ADP-ispinesib complex suffered from pseudo-merohedral twinning and revealed translational noncrystallographic symmetry, leading to challenges in data processing, space-group assignment and structure solution as well as in refinement. These complications may explain the lack of available structural information for this important agent and its analogues. The present structure represents the best interpretation of these data based on extensive data-reduction, structure-solution and refinement trials.
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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.