4v05 › Citations

Structural insights into FGFR kinase isoform selectivity: diverse binding modes of AZD4547 and ponatinib in complex with FGFR1 and FGFR4.

Tucker JA, Klein T, Breed J, Breeze AL, Overman R, Phillips C, Norman RA
Structure 22 1764-1774 (2014)
Related entries: 4uxq, 4v01, 4v04

Cited: 47 times
EuropePMC logo PMID: 25465127

Abstract

The fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases has been implicated in a wide variety of cancers. Despite a high level of sequence homology in the ATP-binding site, the majority of reported inhibitors are selective for the FGFR1-3 isoforms and display much reduced potency toward FGFR4, an exception being the Bcr-Abl inhibitor ponatinib. Here we present the crystal structure of the FGFR4 kinase domain and show that both FGFR1 and FGFR4 kinase domains in complex with ponatinib adopt a DFG-out activation loop conformation. Comparison with the structure of FGFR1 in complex with the candidate drug AZD4547, combined with kinetic characterization of the binding of ponatinib and AZD4547 to FGFR1 and FGFR4, sheds light on the observed differences in selectivity profiles and provides a rationale for developing FGFR4-selective inhibitors.

Reviews - 4v05 mentioned but not cited (4)

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Articles - 4v05 mentioned but not cited (11)

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  10. Discovery of a series of dimethoxybenzene FGFR inhibitors with 5H-pyrrolo[2,3-b]pyrazine scaffold: structure-activity relationship, crystal structural characterization and in vivo study. Wei P, Liu B, Wang R, Gao Y, Li L, Ma Y, Qian Z, Chen Y, Cheng M, Geng M, Shen J, Zhao D, Ai J, Xiong B. Acta Pharm Sin B 9 351-368 (2019)
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Reviews citing this publication (9)

  1. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives. Zhong L, Li Y, Xiong L, Wang W, Wu M, Yuan T, Yang W, Tian C, Miao Z, Wang T, Yang S. Signal Transduct Target Ther 6 201 (2021)
  2. Management of advanced non-small cell lung cancers with known mutations or rearrangements: latest evidence and treatment approaches. Shea M, Costa DB, Rangachari D. Ther Adv Respir Dis 10 113-129 (2016)
  3. FGF19-FGFR4 Signaling in Hepatocellular Carcinoma. Raja A, Park I, Haq F, Ahn SM. Cells 8 E536 (2019)
  4. FGFR-TKI resistance in cancer: current status and perspectives. Yue S, Li Y, Chen X, Wang J, Li M, Chen Y, Wu D. J Hematol Oncol 14 23 (2021)
  5. The FGF/FGFR System in Breast Cancer: Oncogenic Features and Therapeutic Perspectives. Santolla MF, Maggiolini M. Cancers (Basel) 12 E3029 (2020)
  6. An overview of the binding models of FGFR tyrosine kinases in complex with small molecule inhibitors. Cheng W, Wang M, Tian X, Zhang X. Eur J Med Chem 126 476-490 (2017)
  7. 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)
  8. Evaluation of Substituted Pyrazole-Based Kinase Inhibitors in One Decade (2011-2020): Current Status and Future Prospects. El-Gamal MI, El-Gamal MI, Zaraei SO, Madkour MM, Anbar HS. Molecules 27 330 (2022)
  9. Making way for suppressing the FGF19/FGFR4 axis in cancer. Prieto-Dominguez N, Shull AY, Teng Y. Future Med Chem 10 2457-2470 (2018)

Articles citing this publication (23)

  1. Landscape of activating cancer mutations in FGFR kinases and their differential responses to inhibitors in clinical use. Patani H, Bunney TD, Thiyagarajan N, Norman RA, Ogg D, Breed J, Ashford P, Potterton A, Edwards M, Williams SV, Thomson GS, Pang CS, Knowles MA, Breeze AL, Orengo C, Phillips C, Katan M. Oncotarget 7 24252-24268 (2016)
  2. Illuminating the molecular mechanisms of tyrosine kinase inhibitor resistance for the FGFR1 gatekeeper mutation: the Achilles' heel of targeted therapy. Sohl CD, Ryan MR, Luo B, Frey KM, Anderson KS. ACS Chem Biol 10 1319-1329 (2015)
  3. Dual Targeting of PDGFRα and FGFR1 Displays Synergistic Efficacy in Malignant Rhabdoid Tumors. Wong JP, Todd JR, Finetti MA, McCarthy F, Broncel M, Vyse S, Luczynski MT, Crosier S, Ryall KA, Holmes K, Payne LS, Daley F, Wai P, Jenks A, Tanos B, Tan AC, Natrajan RC, Williamson D, Huang PH. Cell Rep 17 1265-1275 (2016)
  4. Fibroblast growth factor receptor 3 isoforms: Novel therapeutic targets for hepatocellular carcinoma? Paur J, Nika L, Maier C, Moscu-Gregor A, Kostka J, Huber D, Mohr T, Heffeter P, Schrottmaier WC, Kappel S, Kandioler D, Holzmann K, Marian B, Berger W, Grusch M, Grasl-Kraupp B. Hepatology 62 1767-1778 (2015)
  5. FGFR4 phosphorylates MST1 to confer breast cancer cells resistance to MST1/2-dependent apoptosis. Turunen SP, von Nandelstadh P, Öhman T, Gucciardo E, Seashore-Ludlow B, Martins B, Rantanen V, Li H, Höpfner K, Östling P, Varjosalo M, Lehti K. Cell Death Differ 26 2577-2593 (2019)
  6. Structural and dynamic insights into the energetics of activation loop rearrangement in FGFR1 kinase. Klein T, Vajpai N, Phillips JJ, Davies G, Holdgate GA, Phillips C, Tucker JA, Norman RA, Scott AD, Higazi DR, Lowe D, Thompson GS, Breeze AL. Nat Commun 6 7877 (2015)
  7. Ponatinib (AP24534) inhibits MEKK3-KLF signaling and prevents formation and progression of cerebral cavernous malformations. Choi JP, Wang R, Yang X, Wang X, Wang L, Ting KK, Foley M, Cogger V, Yang Z, Liu F, Han Z, Liu R, Baell J, Zheng X. Sci Adv 4 eaau0731 (2018)
  8. Crystal Structure of the FGFR4/LY2874455 Complex Reveals Insights into the Pan-FGFR Selectivity of LY2874455. Wu D, Guo M, Philips MA, Qu L, Jiang L, Li J, Chen X, Chen Z, Chen L, Chen Y. PLoS One 11 e0162491 (2016)
  9. 2-Formylpyridyl Ureas as Highly Selective Reversible-Covalent Inhibitors of Fibroblast Growth Factor Receptor 4. Knoepfel T, Furet P, Mah R, Buschmann N, Leblanc C, Ripoche S, Graus-Porta D, Wartmann M, Galuba I, Fairhurst RA. ACS Med Chem Lett 9 215-220 (2018)
  10. Fibroblast growth factor receptor 1 antagonism attenuates lipopolysaccharide-induced activation of hepatic stellate cells via suppressing inflammation. Lou D, Han J, Zhou L, Ma H, Xv J, Shou J, Xu Z, Jiang L, Qian Y. Exp Ther Med 16 2909-2916 (2018)
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  12. Approaches to selective fibroblast growth factor receptor 4 inhibition through targeting the ATP-pocket middle-hinge region. Fairhurst RA, Knoepfel T, Leblanc C, Buschmann N, Gaul C, Blank J, Galuba I, Trappe J, Zou C, Voshol J, Genick C, Brunet-Lefeuvre P, Bitsch F, Graus-Porta D, Furet P. Medchemcomm 8 1604-1613 (2017)
  13. Theoretical studies on FGFR isoform selectivity of FGFR1/FGFR4 inhibitors by molecular dynamics simulations and free energy calculations. Fu W, Chen L, Wang Z, Kang Y, Wu C, Xia Q, Liu Z, Zhou J, Liang G, Cai Y. Phys Chem Chem Phys 19 3649-3659 (2017)
  14. AZD4547 Attenuates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting Inflammation: The Role of FGFR1 in Renal Tubular Epithelial Cells. Chen X, Zhang X, Xu J, Zhao Y, Bao J, Zheng Z, Han J. Drug Des Devel Ther 14 833-844 (2020)
  15. Mutation Detection of Fibroblast Growth Factor Receptor 3 for Infiltrative Hepatocellular Carcinoma by Whole-Exome Sequencing. Yan X, Shao C, Chen C, Chen J, Gu S, Huang L, Fu X, Zhao H, Qiu Y. Dig Dis Sci 62 407-417 (2017)
  16. Anti-Tumor Activity of AZD4547 Against NTRK1 Fusion Positive Cancer Cells Through Inhibition of NTRKs. Cho H, Kim N, Murakami T, Sim T. Front Oncol 11 757598 (2021)
  17. Computational Simulation Studies on the Binding Selectivity of 1-(1H-Benzimidazol-5-yl)-5-aminopyrazoles in Complexes with FGFR1 and FGFR4. Pan YL, Liu YL, Chen JZ. Molecules 23 E767 (2018)
  18. Discovery of Orally Bioavailable FGFR2/FGFR3 Dual Inhibitors via Structure-Guided Scaffold Repurposing Approach. Nguyen MH, Ye HF, Xu Y, Truong L, Horsey A, Zhao P, Styduhar ED, Frascella M, Leffet L, Federowicz K, Behshad E, Wang A, Zhang K, Witten MR, Qi C, Jalluri R, Lai CT, Atasoylu O, Harris JJ, Hess R, Lin L, Zhang G, Covington M, Diamond S, Yao W, Vechorkin O. ACS Med Chem Lett 14 312-318 (2023)
  19. Exploring the endogenous potential of Hemidesmus indicus against breast cancer using in silico studies and quantification of 2-hydroxy-4-methoxy benzaldehyde through RP-HPLC. Bansod AA, Ramasamy G, Nathan B, Kandhasamy R, Palaniappan M, Vichangal Pridiuldi S. 3 Biotech 11 235 (2021)
  20. Discovery of a new potent oxindole multi-kinase inhibitor among a series of designed 3-alkenyl-oxindoles with ancillary carbonic anhydrase inhibitory activity as antiproliferative agents. Ismail RSM, El Kerdawy AM, Soliman DH, Georgey HH, Abdel Gawad NM, Angeli A, Supuran CT. BMC Chem 17 81 (2023)
  21. Elucidating the potential effects of point mutations on FGFR3 inhibitor resistance via combined molecular dynamics simulation and community network analysis. Liu B, Ding J, Liu Y, Wu J, Wu X, Chen Q, Li W. J Comput Aided Mol Des 37 325-338 (2023)
  22. Inhibition of Cancer Cell Proliferation and Bacterial Growth by Silver(I) Complexes Bearing a CH3-Substituted Thiadiazole-Based Thioamide. Varna D, Geromichalou E, Karlioti G, Papi R, Dalezis P, Hatzidimitriou AG, Psomas G, Choli-Papadopoulou T, Trafalis DT, Angaridis PA. Molecules 28 336 (2023)
  23. Receptor-based pharmacophore modeling, molecular docking, synthesis and biological evaluation of novel VEGFR-2, FGFR-1, and BRAF multi-kinase inhibitors. Abdel-Mohsen HT, Ibrahim MA, Nageeb AM, El Kerdawy AM. BMC Chem 18 42 (2024)


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