42. Myers MR, Setzer NN, Spada AP et al (1997) The preparation and SAR of 4-(anilino),
4-(phenoxy), and 4-(thiophenoxy)-quinazolines: inhibitors of p56(lck) and EGF-R tyorsine
kinase activity. Bioorg Med Chem Lett 7:417–420. https://doi.org/10.1016/S0960-894X(97)
00034-6
43. Barker AJ, Gibson KH, Grundy W et al (2001) Studies leading to the identification of ZD1839
(Iressa): an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor
targeted to the treatment of cancer. Bioorg Med Chem Lett 11:1911–1914. https://doi.org/10.
1016/S0960-894X(01)00344-4
44. Böhm H-J, Banner D, Bendels S et al (2004) Fluorine in medicinal chemistry. Chembiochem
5:637–643. https://doi.org/10.1002/cbic.200301023
45. Gillis EP, Eastman KJ, Hill MD et al (2015) Applications of fluorine in medicinal chemistry.
J Med Chem 58:8315–8359. https://doi.org/10.1021/acs.jmedchem.5b00258
46. Woodburn JR (1998) EGF receptor tyrosine kinase inhibitors as anti-cancer agents –
pre-clinical and early clinical profile of ZD 1839. Cell Mol Biol Lett 3:348–349
47. Palmer BD, Trumpp-Kallmeyer S, Fry DW et al (1997) Tyrosine kinase inhibitors. 11. Soluble
analogues of pyrrolo- and pyrazoloquinazolines as epidermal growth factor receptor inhibitors:
synthesis. Biological evaluation, and modeling of the mode of binding. J Med Chem
40:1519–1529. https://doi.org/10.1021/jm960789h
48. Zheng J, Trafny EA, Knighton DR et al (1993) 2.2 angstrom refined crystal structure of the
catalytic subunit of cAMP-dependent protein kinase complexed with MnATP and a peptide
inhibitor. Acta Crystallogr D Biol Crystallogr 49:362–365
49. Moyer JD, Barbacci EG, Iwata KK et al (1997) Induction of apoptosis and cell cycle arrest by
CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Res
57:4838–4848
50. Stamos J, Sliwkowski MX, Eigenbrot C (2002) Structure of the epidermal growth factor
receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor. J Biol
Chem 277:46265–46272. https://doi.org/10.1074/jbc.M207135200
51. Cohen MH (2003) FDA drug approval summary: Gefitinib (ZD1839) (Iressa(R)) tablets.
Oncologist 8:303–306. https://doi.org/10.1634/theoncologist.8-4-303
52. Cohen M, Johnson J, Chen Y et al (2005) FDA drug approval summary: Erlotinib (Tarceva
®
)
tablets. Oncologist 10:461–466
53. Herbst RS, Fukuoka M, Baselga J (2004) Gefitinib – a novel targeted approach to treating
cancer. Nat Rev Cancer 4:956–965. https://doi.org/10.1038/nrc1506
54. Juchum M, Gunther M, Laufer SA (2014) Fighting cancer drug resistance: opportunities and
challenges for mutation-specific EGFR inhibitors. Drug Resist Updat 20:12–28. https://doi.
org/10.1016/j.drup.2015.05.002
55. Ohashi K, Maruvka YE, Michor F, Pao W (2013) Epidermal growth factor receptor tyrosine
kinase inhibitor-resistant disease. J Clin Oncol 31:1070–1080
56. Fridlyand J, Simon RM, Walrath JC et al (2013) Considerations for the successful
co-development of targeted cancer therapies and companion diagnostics. Nat Rev Drug
Discov 12:743–755. https://doi.org/10.1038/nrd4101
57. Vargas AJ, Harris CC (2016) Biomarker development in the precision medicine era: lung
cancer as a case study. Nat Rev Cancer 16:525–537. https://doi.org/10.1038/nrc.2016.56
58. Lynch TJ, Bell DW, Sordella R et al (2004) Activating mutations in the epidermal growth
factor receptor underlying responsiveness of non–small-cell lung cancer to gefitinib. N Engl J
Med 350:2129–2139. https://doi.org/10.1056/NEJMoa1109400
59. Laufer S, Bajorath J (2015) Advancing the kinase field: new targets and second generation
inhibitors. J Med Chem 58:1. https://doi.org/10.1021/jm5018708
60. Yun C, Mengwasser KE, Toms AV et al (2008) The T790M mutation in EGFR kinase causes
drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A 105:2070–2075.
https://doi.org/10.1073/pnas.0709662105
61. Ma C, Wei S, Song Y (2011) T790M and acquired resistance of EGFR TKI: a literature review
of clinical reports. J Thorac Dis 3:10–18
Case Study on Receptor Tyrosine Kinases EGFR, VEGFR, and PDGFR
195
4-(phenoxy), and 4-(thiophenoxy)-quinazolines: inhibitors of p56(lck) and EGF-R tyorsine
kinase activity. Bioorg Med Chem Lett 7:417–420. https://doi.org/10.1016/S0960-894X(97)
00034-6
43. Barker AJ, Gibson KH, Grundy W et al (2001) Studies leading to the identification of ZD1839
(Iressa): an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor
targeted to the treatment of cancer. Bioorg Med Chem Lett 11:1911–1914. https://doi.org/10.
1016/S0960-894X(01)00344-4
44. Böhm H-J, Banner D, Bendels S et al (2004) Fluorine in medicinal chemistry. Chembiochem
5:637–643. https://doi.org/10.1002/cbic.200301023
45. Gillis EP, Eastman KJ, Hill MD et al (2015) Applications of fluorine in medicinal chemistry.
J Med Chem 58:8315–8359. https://doi.org/10.1021/acs.jmedchem.5b00258
46. Woodburn JR (1998) EGF receptor tyrosine kinase inhibitors as anti-cancer agents –
pre-clinical and early clinical profile of ZD 1839. Cell Mol Biol Lett 3:348–349
47. Palmer BD, Trumpp-Kallmeyer S, Fry DW et al (1997) Tyrosine kinase inhibitors. 11. Soluble
analogues of pyrrolo- and pyrazoloquinazolines as epidermal growth factor receptor inhibitors:
synthesis. Biological evaluation, and modeling of the mode of binding. J Med Chem
40:1519–1529. https://doi.org/10.1021/jm960789h
48. Zheng J, Trafny EA, Knighton DR et al (1993) 2.2 angstrom refined crystal structure of the
catalytic subunit of cAMP-dependent protein kinase complexed with MnATP and a peptide
inhibitor. Acta Crystallogr D Biol Crystallogr 49:362–365
49. Moyer JD, Barbacci EG, Iwata KK et al (1997) Induction of apoptosis and cell cycle arrest by
CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Res
57:4838–4848
50. Stamos J, Sliwkowski MX, Eigenbrot C (2002) Structure of the epidermal growth factor
receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor. J Biol
Chem 277:46265–46272. https://doi.org/10.1074/jbc.M207135200
51. Cohen MH (2003) FDA drug approval summary: Gefitinib (ZD1839) (Iressa(R)) tablets.
Oncologist 8:303–306. https://doi.org/10.1634/theoncologist.8-4-303
52. Cohen M, Johnson J, Chen Y et al (2005) FDA drug approval summary: Erlotinib (Tarceva
®
)
tablets. Oncologist 10:461–466
53. Herbst RS, Fukuoka M, Baselga J (2004) Gefitinib – a novel targeted approach to treating
cancer. Nat Rev Cancer 4:956–965. https://doi.org/10.1038/nrc1506
54. Juchum M, Gunther M, Laufer SA (2014) Fighting cancer drug resistance: opportunities and
challenges for mutation-specific EGFR inhibitors. Drug Resist Updat 20:12–28. https://doi.
org/10.1016/j.drup.2015.05.002
55. Ohashi K, Maruvka YE, Michor F, Pao W (2013) Epidermal growth factor receptor tyrosine
kinase inhibitor-resistant disease. J Clin Oncol 31:1070–1080
56. Fridlyand J, Simon RM, Walrath JC et al (2013) Considerations for the successful
co-development of targeted cancer therapies and companion diagnostics. Nat Rev Drug
Discov 12:743–755. https://doi.org/10.1038/nrd4101
57. Vargas AJ, Harris CC (2016) Biomarker development in the precision medicine era: lung
cancer as a case study. Nat Rev Cancer 16:525–537. https://doi.org/10.1038/nrc.2016.56
58. Lynch TJ, Bell DW, Sordella R et al (2004) Activating mutations in the epidermal growth
factor receptor underlying responsiveness of non–small-cell lung cancer to gefitinib. N Engl J
Med 350:2129–2139. https://doi.org/10.1056/NEJMoa1109400
59. Laufer S, Bajorath J (2015) Advancing the kinase field: new targets and second generation
inhibitors. J Med Chem 58:1. https://doi.org/10.1021/jm5018708
60. Yun C, Mengwasser KE, Toms AV et al (2008) The T790M mutation in EGFR kinase causes
drug resistance by increasing the affinity for ATP. Proc Natl Acad Sci U S A 105:2070–2075.
https://doi.org/10.1073/pnas.0709662105
61. Ma C, Wei S, Song Y (2011) T790M and acquired resistance of EGFR TKI: a literature review
of clinical reports. J Thorac Dis 3:10–18
Case Study on Receptor Tyrosine Kinases EGFR, VEGFR, and PDGFR
195