4. Guida T, Anaganti S, Provitera L et al (2007) Sorafenib inhibits imatinib-resistant KIT and
platelet-derived growth factor receptor beta gatekeeper mutants. Clin Cancer Res
13:3363–3369. https://doi.org/10.1158/1078-0432.CCR-06-2667
5. Liang L, Yan X-E, Yin Y, Yun C-H (2016) Structural and biochemical studies of the PDGFRA
kinase domain. Biochem Biophys Res Commun 477:667–672. https://doi.org/10.1016/j.bbrc.
2016.06.117
6. Shi L, Zhou J, Wu J et al (2016) Anti-angiogenic therapy: strategies to develop potent
VEGFR-2 tyrosine kinase inhibitors and future prospect. Curr Med Chem 23:1000–1040
7. Wu P, Nielsen TE, Clausen MH (2015) FDA-approved small-molecule kinase inhibitors.
Trends Pharmacol Sci 36:422–439. https://doi.org/10.1016/j.tips.2015.04.005
8. Vajpai N, Strauss A, Fendrich G et al (2008) Solution conformations and dynamics of ABL
kinase-inhibitor complexes determined by NMR substantiate the different binding modes of
imatinib/nilotinib and dasatinib. J Biol Chem 283:18292–18302. https://doi.org/10.1074/jbc.
M801337200
9. Dietrich J, Hulme C, Hurley LH (2010) The design, synthesis, and evaluation of 8 hybrid
DFG-out allosteric kinase inhibitors: a structural analysis of the binding interactions of
Gleevec, Nexavar, and BIRB-796. Bioorg Med Chem 18:5738–5748. https://doi.org/10.
1016/j.bmc.2010.05.063
10. Wu P, Nielsen TE, Clausen MH (2016) Small-molecule kinase inhibitors: an analysis of
FDA-approved drugs. Drug Discov Today 21:5–10. https://doi.org/10.1016/j.drudis.2015.
07.008
11. Muralidhara C, Ramachandran A, Jain VK (2012) Abstract 3683: Crenolanib, a novel type I,
mutant-specific inhibitor of class III receptor tyrosine kinases, preferentially binds to phosphorylated kinases. Cancer Res 72:3683–3683. https://doi.org/10.1158/1538-7445.AM20123683
12. Bazley LA, Gullick WJ (2005) The epidermal growth factor receptor family. Endocr Relat
Cancer 12:17–28. https://doi.org/10.1677/erc.1.01032
13. Wieduwilt MJ, Moasser MM (2008) The epidermal growth factor receptor family: biology
driving targeted therapeutics. Cell Mol Life Sci 65:1566–1584. https://doi.org/10.1007/
s00018-008-7440-8
14. Tebbutt N, Pedersen MW, Johns TG (2013) Targeting the ERBB family in cancer: couples
therapy. Nat Rev Cancer 13:663–673. https://doi.org/10.1038/nrc3559
15. Zhang H, Berezov A, Wang Q et al (2007) ErbB receptors: from oncogenes to targeted cancer
therapies. J Clin Investig 117:2051–2058
16. Graus-Porta D, Beerli RR, Daly JM, Hynes NE (1997) ErbB-2, the preferred
heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. EMBO J
16:1647–1655. https://doi.org/10.1093/emboj/16.7.1647
17. Hynes NE, MacDonald G (2009) ErbB receptors and signaling pathways in cancer. Curr Opin
Cell Biol 21:177–184
18. Nyati M, Morgan M, Feng F, Lawrence T (2006) Integration of EGFR inhibitors with
radiochemotherapy. Nat Rev Cancer 6:876–885. https://doi.org/10.1038/nrc1953
19. Gao S, Mark K, Leslie K (2007) Mutations in the EGFR kinase domain mediate STAT3
activation via IL-6 production in human lung adenocarcinomas. J Clin Investig
117:3846–3856. https://doi.org/10.1172/JCI31871.3846
20. Wang Q, Greene MI (2008) Mechanisms of resistance to ErbB-targeted cancer therapeutics.
J Clin Investig 118:2389–2392. https://doi.org/10.1172/JCI36260
21. Hickey K, Grehan D, Reid IM et al (1994) Expression of epidermal growth factor receptor and
proliferating cell nuclear antigen predicts response of esophageal squamous cell carcinoma to
chemoradiotherapy. Cancer 74:1693–1698. https://doi.org/10.1002/1097-0142(19940915)
74:6<1693::AID-CNCR2820740609>3.0.CO;2-#
22. Liu B, Bernard B, Wu JH (2006) Impact of EGFR point mutations on the sensitivity to
gefitinib : insights from comparative structural analyses and molecular dynamics simulations.
Proteins Struct Funct Bioinf 65:331–346. https://doi.org/10.1002/prot
Case Study on Receptor Tyrosine Kinases EGFR, VEGFR, and PDGFR
193
platelet-derived growth factor receptor beta gatekeeper mutants. Clin Cancer Res
13:3363–3369. https://doi.org/10.1158/1078-0432.CCR-06-2667
5. Liang L, Yan X-E, Yin Y, Yun C-H (2016) Structural and biochemical studies of the PDGFRA
kinase domain. Biochem Biophys Res Commun 477:667–672. https://doi.org/10.1016/j.bbrc.
2016.06.117
6. Shi L, Zhou J, Wu J et al (2016) Anti-angiogenic therapy: strategies to develop potent
VEGFR-2 tyrosine kinase inhibitors and future prospect. Curr Med Chem 23:1000–1040
7. Wu P, Nielsen TE, Clausen MH (2015) FDA-approved small-molecule kinase inhibitors.
Trends Pharmacol Sci 36:422–439. https://doi.org/10.1016/j.tips.2015.04.005
8. Vajpai N, Strauss A, Fendrich G et al (2008) Solution conformations and dynamics of ABL
kinase-inhibitor complexes determined by NMR substantiate the different binding modes of
imatinib/nilotinib and dasatinib. J Biol Chem 283:18292–18302. https://doi.org/10.1074/jbc.
M801337200
9. Dietrich J, Hulme C, Hurley LH (2010) The design, synthesis, and evaluation of 8 hybrid
DFG-out allosteric kinase inhibitors: a structural analysis of the binding interactions of
Gleevec, Nexavar, and BIRB-796. Bioorg Med Chem 18:5738–5748. https://doi.org/10.
1016/j.bmc.2010.05.063
10. Wu P, Nielsen TE, Clausen MH (2016) Small-molecule kinase inhibitors: an analysis of
FDA-approved drugs. Drug Discov Today 21:5–10. https://doi.org/10.1016/j.drudis.2015.
07.008
11. Muralidhara C, Ramachandran A, Jain VK (2012) Abstract 3683: Crenolanib, a novel type I,
mutant-specific inhibitor of class III receptor tyrosine kinases, preferentially binds to phosphorylated kinases. Cancer Res 72:3683–3683. https://doi.org/10.1158/1538-7445.AM20123683
12. Bazley LA, Gullick WJ (2005) The epidermal growth factor receptor family. Endocr Relat
Cancer 12:17–28. https://doi.org/10.1677/erc.1.01032
13. Wieduwilt MJ, Moasser MM (2008) The epidermal growth factor receptor family: biology
driving targeted therapeutics. Cell Mol Life Sci 65:1566–1584. https://doi.org/10.1007/
s00018-008-7440-8
14. Tebbutt N, Pedersen MW, Johns TG (2013) Targeting the ERBB family in cancer: couples
therapy. Nat Rev Cancer 13:663–673. https://doi.org/10.1038/nrc3559
15. Zhang H, Berezov A, Wang Q et al (2007) ErbB receptors: from oncogenes to targeted cancer
therapies. J Clin Investig 117:2051–2058
16. Graus-Porta D, Beerli RR, Daly JM, Hynes NE (1997) ErbB-2, the preferred
heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. EMBO J
16:1647–1655. https://doi.org/10.1093/emboj/16.7.1647
17. Hynes NE, MacDonald G (2009) ErbB receptors and signaling pathways in cancer. Curr Opin
Cell Biol 21:177–184
18. Nyati M, Morgan M, Feng F, Lawrence T (2006) Integration of EGFR inhibitors with
radiochemotherapy. Nat Rev Cancer 6:876–885. https://doi.org/10.1038/nrc1953
19. Gao S, Mark K, Leslie K (2007) Mutations in the EGFR kinase domain mediate STAT3
activation via IL-6 production in human lung adenocarcinomas. J Clin Investig
117:3846–3856. https://doi.org/10.1172/JCI31871.3846
20. Wang Q, Greene MI (2008) Mechanisms of resistance to ErbB-targeted cancer therapeutics.
J Clin Investig 118:2389–2392. https://doi.org/10.1172/JCI36260
21. Hickey K, Grehan D, Reid IM et al (1994) Expression of epidermal growth factor receptor and
proliferating cell nuclear antigen predicts response of esophageal squamous cell carcinoma to
chemoradiotherapy. Cancer 74:1693–1698. https://doi.org/10.1002/1097-0142(19940915)
74:6<1693::AID-CNCR2820740609>3.0.CO;2-#
22. Liu B, Bernard B, Wu JH (2006) Impact of EGFR point mutations on the sensitivity to
gefitinib : insights from comparative structural analyses and molecular dynamics simulations.
Proteins Struct Funct Bioinf 65:331–346. https://doi.org/10.1002/prot
Case Study on Receptor Tyrosine Kinases EGFR, VEGFR, and PDGFR
193