23. Abella JV, Park M (2009) Breakdown of endocytosis in the oncogenic activation of receptor
tyrosine kinases. Am J Physiol Endocrinol Metab 296:E973–E984. https://doi.org/10.1152/
ajpendo.90857.2008
24. Meierjohann S, Hufnagel A, Wende E et al (2010) MMP13 mediates cell cycle progression in
melanocytes and melanoma cells: in vitro studies of migration and proliferation. Mol Cancer
9:201. https://doi.org/10.1186/1476-4598-9-201
25. Mendelsohn J (2001) The epidermal growth factor receptor as a target for cancer therapy.
Endocr Relat Cancer 8:3–9
26. Pines G, Huang PH, Zwang Y et al (2010) EGFRvIV: a previously uncharacterized oncogenic
mutant reveals a kinase autoinhibitory mechanism. Oncogene 29:5850–5860. https://doi.org/
10.1038/onc.2010.313
27. Umekita Y, Ohi Y, Sagara Y, Yoshida H (2000) Co-expression of epidermal growth factor
receptor and transforming growth factor-alpha predicts worse prognosis in breast-cancer
patients. Int J Cancer 89:484–487. https://doi.org/10.1002/1097-0215(20001120)89:6<484::
AID-IJC3>3.0.CO;2-S
28. Chong CR, Jänne PA (2013) The quest to overcome resistance to EGFR-targeted therapies in
cancer. Nat Med 19:1389–1400. https://doi.org/10.1038/nm.3388
29. Nawaz K, Webster RM (2016) The non-small-cell lung cancer drug market. Nat Rev Drug
Discov 15:229–230. https://doi.org/10.1038/nrd.2016.42
30. Dienstmann R, De Dosso S, Felip E, Tabernero J (2012) Drug development to overcome
resistance to EGFR inhibitors in lung and colorectal cancer. Mol Oncol 6:15–26
31. Moreira C, Kaklamani V (2010) Lapatinib and breast cancer: current indications and outlook
for the future. Expert Rev Anticancer Ther 10:1171–1182. https://doi.org/10.1586/era.10.113
32. Ton GN, Banaszynski ME, Kolesar JM (2013) Vandetanib: a novel targeted therapy for the
treatment of metastatic or locally advanced medullary thyroid cancer. Am J Health Syst Pharm
70:849–855
33. Woodburn JR (1999) The epidermal growth factor receptor and its inhibition in cancer
therapy. Pharmacol Ther 82:241–250. https://doi.org/10.1016/S0163-7258(98)00045-X
34. Ward WHJ, Cook PN, Slater AM et al (1994) Epidermal growth factor receptor tyrosine
kinase. Biochem Pharmacol 48:659–666. https://doi.org/10.1016/0006-2952(94)90042-6
35. Fry DW, Kraker AJ, McMichael A et al (1994) A specific inhibitor of the epidermal growth
factor receptor tyrosine kinase. Science 265:1093–1095. https://doi.org/10.1126/science.
8066447
36. Rewcastle GW, Denny WA, Bridges AJ et al (1995) Synthesis and structure-activity relationships for 4-[(phenylmethyl) amino]-and 4-(phenylamino) quinazolines as potent adenosine
5
0 -triphosphate binding site inhibitors of the tyrosine kinase domain of the epidermal growth
factor receptor. J Med Chem 38:3482–3487
37. Wakeling AE, Barker AJ, Davies DH et al (1996) Specific inhibition of epidermal growth
factor receptor tyrosine kinase by 4-anilinoquinazolines A.E. Breast Cancer Res Treat
38:67–73
38. Denny WA, Rewcastle GW, Bridges AJ et al (1996) Structure-activity relationships for
4-anilinoquinazolines as potent inhibitors at the ATP binding site of the epidermal growth
factor receptor in vitro. Clin Exp Pharmacol Physiol 23:424–427
39. Bridges AJ, Zhou H, Cody DR et al (1996) Tyrosine kinase inhibitors 8. An unusually steep
structure-activity relationship for analogues of 4-(3-bromoanilino)-6,7-dimethoxyquinazoline
(PD 153035), a potent inhibitor of the epidermal growth factor receptor. J Med Chem
39:267–276
40. Barreiro EJ, Kümmerle AE, Fraga CAM (2011) The methylation effect in medicinal chemistry. Chem Rev 111:5215–5246
41. Myers MR, Setzer N, Spada AP et al (1997) The synthesis and SAR of new 4-(N-alkyl-Nphenyl)amino-6,7-dimethoxyquinazolines and 4-(N-alkyl-N-phenyl)amino-pyrazolo[3,4-d]
pyrimidines, inhibitors of CSF-1R tyrosine kinase activity. Bioorg Med Chem Lett 7:421–424
194
L. M. Lima et al.
tyrosine kinases. Am J Physiol Endocrinol Metab 296:E973–E984. https://doi.org/10.1152/
ajpendo.90857.2008
24. Meierjohann S, Hufnagel A, Wende E et al (2010) MMP13 mediates cell cycle progression in
melanocytes and melanoma cells: in vitro studies of migration and proliferation. Mol Cancer
9:201. https://doi.org/10.1186/1476-4598-9-201
25. Mendelsohn J (2001) The epidermal growth factor receptor as a target for cancer therapy.
Endocr Relat Cancer 8:3–9
26. Pines G, Huang PH, Zwang Y et al (2010) EGFRvIV: a previously uncharacterized oncogenic
mutant reveals a kinase autoinhibitory mechanism. Oncogene 29:5850–5860. https://doi.org/
10.1038/onc.2010.313
27. Umekita Y, Ohi Y, Sagara Y, Yoshida H (2000) Co-expression of epidermal growth factor
receptor and transforming growth factor-alpha predicts worse prognosis in breast-cancer
patients. Int J Cancer 89:484–487. https://doi.org/10.1002/1097-0215(20001120)89:6<484::
AID-IJC3>3.0.CO;2-S
28. Chong CR, Jänne PA (2013) The quest to overcome resistance to EGFR-targeted therapies in
cancer. Nat Med 19:1389–1400. https://doi.org/10.1038/nm.3388
29. Nawaz K, Webster RM (2016) The non-small-cell lung cancer drug market. Nat Rev Drug
Discov 15:229–230. https://doi.org/10.1038/nrd.2016.42
30. Dienstmann R, De Dosso S, Felip E, Tabernero J (2012) Drug development to overcome
resistance to EGFR inhibitors in lung and colorectal cancer. Mol Oncol 6:15–26
31. Moreira C, Kaklamani V (2010) Lapatinib and breast cancer: current indications and outlook
for the future. Expert Rev Anticancer Ther 10:1171–1182. https://doi.org/10.1586/era.10.113
32. Ton GN, Banaszynski ME, Kolesar JM (2013) Vandetanib: a novel targeted therapy for the
treatment of metastatic or locally advanced medullary thyroid cancer. Am J Health Syst Pharm
70:849–855
33. Woodburn JR (1999) The epidermal growth factor receptor and its inhibition in cancer
therapy. Pharmacol Ther 82:241–250. https://doi.org/10.1016/S0163-7258(98)00045-X
34. Ward WHJ, Cook PN, Slater AM et al (1994) Epidermal growth factor receptor tyrosine
kinase. Biochem Pharmacol 48:659–666. https://doi.org/10.1016/0006-2952(94)90042-6
35. Fry DW, Kraker AJ, McMichael A et al (1994) A specific inhibitor of the epidermal growth
factor receptor tyrosine kinase. Science 265:1093–1095. https://doi.org/10.1126/science.
8066447
36. Rewcastle GW, Denny WA, Bridges AJ et al (1995) Synthesis and structure-activity relationships for 4-[(phenylmethyl) amino]-and 4-(phenylamino) quinazolines as potent adenosine
5
0 -triphosphate binding site inhibitors of the tyrosine kinase domain of the epidermal growth
factor receptor. J Med Chem 38:3482–3487
37. Wakeling AE, Barker AJ, Davies DH et al (1996) Specific inhibition of epidermal growth
factor receptor tyrosine kinase by 4-anilinoquinazolines A.E. Breast Cancer Res Treat
38:67–73
38. Denny WA, Rewcastle GW, Bridges AJ et al (1996) Structure-activity relationships for
4-anilinoquinazolines as potent inhibitors at the ATP binding site of the epidermal growth
factor receptor in vitro. Clin Exp Pharmacol Physiol 23:424–427
39. Bridges AJ, Zhou H, Cody DR et al (1996) Tyrosine kinase inhibitors 8. An unusually steep
structure-activity relationship for analogues of 4-(3-bromoanilino)-6,7-dimethoxyquinazoline
(PD 153035), a potent inhibitor of the epidermal growth factor receptor. J Med Chem
39:267–276
40. Barreiro EJ, Kümmerle AE, Fraga CAM (2011) The methylation effect in medicinal chemistry. Chem Rev 111:5215–5246
41. Myers MR, Setzer N, Spada AP et al (1997) The synthesis and SAR of new 4-(N-alkyl-Nphenyl)amino-6,7-dimethoxyquinazolines and 4-(N-alkyl-N-phenyl)amino-pyrazolo[3,4-d]
pyrimidines, inhibitors of CSF-1R tyrosine kinase activity. Bioorg Med Chem Lett 7:421–424
194
L. M. Lima et al.