5am6 Citations

The Effect of Mutations on Drug Sensitivity and Kinase Activity of Fibroblast Growth Factor Receptors: A Combined Experimental and Theoretical Study.

OpenAccess logo EBioMedicine 2 194-204 (2015)
Related entries: 4uwy, 5am7

Cited: 35 times
EuropePMC logo PMID: 26097890

Abstract

Fibroblast growth factor receptors (FGFRs) are recognized therapeutic targets in cancer. We here describe insights underpinning the impact of mutations on FGFR1 and FGFR3 kinase activity and drug efficacy, using a combination of computational calculations and experimental approaches including cellular studies, X-ray crystallography and biophysical and biochemical measurements. Our findings reveal that some of the tested compounds, in particular TKI258, could provide therapeutic opportunity not only for patients with primary alterations in FGFR but also for acquired resistance due to the gatekeeper mutation. The accuracy of the computational methodologies applied here shows a potential for their wider application in studies of drug binding and in assessments of functional and mechanistic impacts of mutations, thus assisting efforts in precision medicine.

Articles - 5am6 mentioned but not cited (4)

  1. Computational Study of Imidazolylporphyrin Derivatives as a Radiopharmaceutical Ligand for Melanoma. Kurniawan F, Kartasasmita RE, Yoshioka N, Mutalib A, Tjahjono DH. Curr Comput Aided Drug Des 14 191-199 (2018)
  2. Design, synthesis, and biological evaluation of 3-vinyl-quinoxalin-2(1H)-one derivatives as novel antitumor inhibitors of FGFR1. Liu Z, Yu S, Chen D, Shen G, Wang Y, Hou L, Lin D, Zhang J, Ye F. Drug Des Devel Ther 10 1489-1500 (2016)
  3. Cadmium SAD phasing at CuKα wavelength. Eliseev IE, Yudenko AN, Ukrainskaya VM, Chakchir OB. F1000Res 8 84 (2019)
  4. PoSSuM v.3: A Major Expansion of the PoSSuM Database for Finding Similar Binding Sites of Proteins. Tsuchiya Y, Yonezawa T, Yamamori Y, Inoura H, Osawa M, Ikeda K, Tomii K. J Chem Inf Model 63 7578-7587 (2023)


Reviews citing this publication (8)

  1. Rapid, accurate, precise and reproducible ligand-protein binding free energy prediction. Wan S, Bhati AP, Zasada SJ, Coveney PV. Interface Focus 10 20200007 (2020)
  2. 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)
  3. A place for precision medicine in bladder cancer: targeting the FGFRs. di Martino E, Tomlinson DC, Williams SV, Knowles MA. Future Oncol 12 2243-2263 (2016)
  4. Structure and Dynamics of the EGF Receptor as Revealed by Experiments and Simulations and Its Relevance to Non-Small Cell Lung Cancer. Martin-Fernandez ML, Clarke DT, Roberts SK, Zanetti-Domingues LC, Gervasio FL. Cells 8 E316 (2019)
  5. 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)
  6. Biological Significance and Targeting of the FGFR Axis in Cancer. Chioni AM, Grose RP. Cancers (Basel) 13 5681 (2021)
  7. Signaling Pathway and Small-Molecule Drug Discovery of FGFR: A Comprehensive Review. Zheng J, Zhang W, Li L, He Y, Wei Y, Dang Y, Nie S, Guo Z. Front Chem 10 860985 (2022)
  8. Structural Alterations in Human Fibroblast Growth Factor Receptors in Carcinogenesis. Mikhaylenko DS, Alekseev BY, Zaletaev DV, Goncharova RI, Nemtsova MV. Biochemistry (Mosc) 83 930-943 (2018)

Articles citing this publication (23)