3hv6 › Citations

Displacement assay for the detection of stabilizers of inactive kinase conformations.

Klüter S, Grütter C, Naqvi T, Rabiller M, Simard JR, Pawar V, Getlik M, Rauh D
J Med Chem 53 357-67 (2010)
Related entries: 3hv3, 3hv4, 3hv5, 3hv7

Cited: 12 times
EuropePMC logo PMID: 19928858

Abstract

Targeting protein kinases with small molecules outside the highly conserved ATP pocket to stabilize inactive kinase conformations is becoming a more desirable approach in kinase inhibitor research, since these molecules have advanced pharmacological properties compared to compounds exclusively targeting the ATP pocket. Traditional screening approaches for kinase inhibitors are often based on enzyme activity, but they may miss inhibitors that stabilize inactive kinase conformations by enriching the active state of the kinase. Here we present the development of a kinase binding assay employing a pyrazolourea type III inhibitor and enzyme fragment complementation (EFC) technology that is suitable to screen stabilizers of enzymatically inactive kinases. To validate this assay system, we report the binding characteristics of a series of kinase inhibitors to inactive p38alpha and JNK2. Additionally, we present protein X-ray crystallography studies to examine the binding modes of potent quinoline-based DFG-out binders in p38alpha.

Articles - 3hv6 mentioned but not cited (4)

  1. Insights from free-energy calculations: protein conformational equilibrium, driving forces, and ligand-binding modes. Huang YM, Chen W, Potter MJ, Chang CE. Biophys J 103 342-351 (2012)
  2. p38α Mitogen-Activated Protein Kinase Is a Druggable Target in Pancreatic Adenocarcinoma. Yang L, Sun X, Ye Y, Lu Y, Zuo J, Liu W, Elcock A, Zhu S. Front Oncol 9 1294 (2019)
  3. Data-Driven Construction of Antitumor Agents with Controlled Polypharmacology. Da C, Zhang D, Stashko M, Vasileiadi E, Parker RE, Minson KA, Huey MG, Huelse JM, Hunter D, Gilbert TSK, Norris-Drouin J, Miley M, Herring LE, Graves LM, DeRyckere D, Earp HS, Graham DK, Frye SV, Wang X, Kireev D. J Am Chem Soc 141 15700-15709 (2019)
  4. Towards good correlation between fragment molecular orbital interaction energies and experimental IC50 for ligand binding: A case study of p38 MAP kinase. Sheng Y, Watanabe H, Maruyama K, Watanabe C, Okiyama Y, Honma T, Fukuzawa K, Tanaka S. Comput Struct Biotechnol J 16 421-434 (2018)


Reviews citing this publication (3)

  1. Proteus in the world of proteins: conformational changes in protein kinases. Rabiller M, Getlik M, Klüter S, Richters A, Tückmantel S, Simard JR, Rauh D. Arch Pharm (Weinheim) 343 193-206 (2010)
  2. Recent Studies on Ponatinib in Cancers Other Than Chronic Myeloid Leukemia. Musumeci F, Greco C, Grossi G, Molinari A, Schenone S. Cancers (Basel) 10 E430 (2018)
  3. Therapeutic Targeting the Allosteric Cysteinome of RAS and Kinase Families. Li L, Meyer C, Zhou ZW, Elmezayen A, Westover K. J Mol Biol 434 167626 (2022)

Articles citing this publication (5)

  1. Paroxetine is a direct inhibitor of g protein-coupled receptor kinase 2 and increases myocardial contractility. Thal DM, Homan KT, Chen J, Wu EK, Hinkle PM, Huang ZM, Chuprun JK, Song J, Gao E, Cheung JY, Sklar LA, Koch WJ, Tesmer JJ. ACS Chem Biol 7 1830-1839 (2012)
  2. Discovery of a potential allosteric ligand binding site in CDK2. Betzi S, Alam R, Martin M, Lubbers DJ, Han H, Jakkaraj SR, Georg GI, Schönbrunn E. ACS Chem Biol 6 492-501 (2011)
  3. Novel approaches for targeting kinases: allosteric inhibition, allosteric activation and pseudokinases. Cowan-Jacob SW, Jahnke W, Knapp S. Future Med Chem 6 541-561 (2014)
  4. Identification of type-II inhibitors using kinase structures. Lovering F, McDonald J, Whitlock GA, Glossop PA, Phillips C, Bent A, Sabnis Y, Ryan M, Fitz L, Lee J, Chang JS, Han S, Kurumbail R, Thorarensen A. Chem Biol Drug Des 80 657-664 (2012)
  5. 'Turn On/Off' fluorescence probe for the screening of unactivated Bruton's tyrosine kinase. Kawahata W, Asami T, Fujii I, Sawa M. Bioorg Med Chem Lett 25 2141-2145 (2015)


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