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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
ErbB family receptors are Class I receptor tyrosine kinases . ERBB2 (also known as HER-2 or NEU) appears to act as an essential partner for the other members of the family without itself being activated by a cognate ligand . Ligands of the ErbB family of receptors are peptides, many of which are generated by proteolytic cleavage of cell-surface proteins. HER/ErbB is the viral counterpart to the receptor tyrosine kinase EGFR. All family members heterodimerize with each other to activate downstream signalling pathways and are aberrantly expressed in many cancers, particularly forms of breast cancer and lung cancer. Mutations in the EGFR are responsible for acquired resistance to tyrosine kinase inhibitor chemotherapeutics.
1. Cockerill S, Stubberfield C, Stables J, Carter M, Guntrip S, Smith K, McKeown S, Shaw R, Topley P, Thomsen L et al.. (2001) Indazolylamino quinazolines and pyridopyrimidines as inhibitors of the EGFr and C-erbB-2. Bioorg. Med. Chem. Lett., 11 (11): 1401-5. [PMID:11378364]
2. Coumar MS, Chu CY, Lin CW, Shiao HY, Ho YL, Reddy R, Lin WH, Chen CH, Peng YH, Leou JS et al.. (2010) Fast-forwarding hit to lead: aurora and epidermal growth factor receptor kinase inhibitor lead identification. J. Med. Chem., 53 (13): 4980-8. [PMID:20550212]
3. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat. Biotechnol., 29 (11): 1046-51. [PMID:22037378]
4. Gaul MD, Guo Y, Affleck K, Cockerill GS, Gilmer TM, Griffin RJ, Guntrip S, Keith BR, Knight WB, Mullin RJ et al.. (2003) Discovery and biological evaluation of potent dual ErbB-2/EGFR tyrosine kinase inhibitors: 6-thiazolylquinazolines. Bioorg. Med. Chem. Lett., 13 (4): 637-40. [PMID:12639547]
5. Gazit A, Osherov N, Posner I, Yaish P, Poradosu E, Gilon C, Levitzki A. (1991) Tyrphostins. 2. Heterocyclic and alpha-substituted benzylidenemalononitrile tyrphostins as potent inhibitors of EGF receptor and ErbB2/neu tyrosine kinases. J. Med. Chem., 34 (6): 1896-907. [PMID:1676428]
6. Gazit A, Yaish P, Gilon C, Levitzki A. (1989) Tyrphostins I: synthesis and biological activity of protein tyrosine kinase inhibitors. J. Med. Chem., 32 (10): 2344-52. [PMID:2552117]
7. Gendreau SB, Ventura R, Keast P, Laird AD, Yakes FM, Zhang W, Bentzien F, Cancilla B, Lutman J, Chu F et al.. (2007) Inhibition of the T790M gatekeeper mutant of the epidermal growth factor receptor by EXEL-7647. Clin. Cancer Res., 13 (12): 3713-23. [PMID:17575237]
8. Goldstein NI, Giorgio NA, Jones ST, Saldanha JW. (2006) Epidermal growth factor; nucleic acids, protein which binds to epidermal growth factor receptors; genetic engineering. Patent number: US7060808. Assignee: Imclone Systems Incorporated. Priority date: 07/06/1995. Publication date: 13/06/2006.
9. Grassot J, Mouchiroud G, Perrière G. (2003) RTKdb: database of Receptor Tyrosine Kinase. Nucleic Acids Res., 31 (1): 353-8. [PMID:12520021]
10. 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 (7): 1647-55. [PMID:9130710]
11. Gundla R, Kazemi R, Sanam R, Muttineni R, Sarma JA, Dayam R, Neamati N. (2008) Discovery of novel small-molecule inhibitors of human epidermal growth factor receptor-2: combined ligand and target-based approach. J. Med. Chem., 51 (12): 3367-77. [PMID:18500794]
12. Kao Y-H, Vanderlaan M. (2006) Her2 antibody composition. Patent number: WO2006033700. Assignee: Genentech Inc.. Priority date: 22/07/2004. Publication date: 30/04/2010.
13. Li D, Ambrogio L, Shimamura T, Kubo S, Takahashi M, Chirieac LR, Padera RF, Shapiro GI, Baum A, Himmelsbach F et al.. (2008) BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene, 27 (34): 4702-11. [PMID:18408761]
14. Liu M, Zhu Z. (2009) Used in treating neoplastic diseases and hyperproliferative disorders. Patent number: US7598350. Assignee: Imclone Llc. Priority date: 19/03/2004. Publication date: 06/10/2009.
15. Marathe P, Tang Y, Sleczka B, Rodrigues D, Gavai A, Wong T, Christopher L, Zhang H. (2010) Preclinical pharmacokinetics and in vitro metabolism of BMS-690514, a potent inhibitor of EGFR and VEGFR2. J Pharm Sci, 99 (8): 3579-93. [PMID:20166197]
16. Nam HJ, Kim HP, Yoon YK, Hur HS, Song SH, Kim MS, Lee GS, Han SW, Im SA, Kim TY et al.. (2011) Antitumor activity of HM781-36B, an irreversible Pan-HER inhibitor, alone or in combination with cytotoxic chemotherapeutic agents in gastric cancer. Cancer Lett., 302 (2): 155-65. [PMID:21306821]
17. Rabindran SK, Discafani CM, Rosfjord EC, Baxter M, Floyd MB, Golas J, Hallett WA, Johnson BD, Nilakantan R, Overbeek E et al.. (2004) Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase. Cancer Res., 64 (11): 3958-65. [PMID:15173008]
18. Rusnak DW, Lackey K, Affleck K, Wood ER, Alligood KJ, Rhodes N, Keith BR, Murray DM, Knight WB, Mullin RJ et al.. (2001) The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo. Mol. Cancer Ther., 1 (2): 85-94. [PMID:12467226]
19. Smaill JB, Rewcastle GW, Loo JA, Greis KD, Chan OH, Reyner EL, Lipka E, Showalter HD, Vincent PW, Elliott WL et al.. (2000) Tyrosine kinase inhibitors. 17. Irreversible inhibitors of the epidermal growth factor receptor: 4-(phenylamino)quinazoline- and 4-(phenylamino)pyrido[3,2-d]pyrimidine-6-acrylamides bearing additional solubilizing functions. J. Med. Chem., 43 (7): 1380-97. [PMID:10753475]
20. Traxler P, Green J, Mett H, Séquin U, Furet P. (1999) Use of a pharmacophore model for the design of EGFR tyrosine kinase inhibitors: isoflavones and 3-phenyl-4(1H)-quinolones. J. Med. Chem., 42 (6): 1018-26. [PMID:10090785]
21. Walter AO, Sjin RT, Haringsma HJ, Ohashi K, Sun J, Lee K, Dubrovskiy A, Labenski M, Zhu Z, Wang Z et al.. (2013) Discovery of a mutant-selective covalent inhibitor of EGFR that overcomes T790M-mediated resistance in NSCLC. Cancer Discov, 3 (12): 1404-15. [PMID:24065731]
22. Wissner A, Fraser HL, Ingalls CL, Dushin RG, Floyd MB, Cheung K, Nittoli T, Ravi MR, Tan X, Loganzo F. (2007) Dual irreversible kinase inhibitors: quinazoline-based inhibitors incorporating two independent reactive centers with each targeting different cysteine residues in the kinase domains of EGFR and VEGFR-2. Bioorg. Med. Chem., 15 (11): 3635-48. [PMID:17416531]
23. Zhang YM, Cockerill S, Guntrip SB, Rusnak D, Smith K, Vanderwall D, Wood E, Lackey K. (2004) Synthesis and SAR of potent EGFR/erbB2 dual inhibitors. Bioorg. Med. Chem. Lett., 14 (1): 111-4. [PMID:14684309]
Database page citation:
Type I RTKs: ErbB (epidermal growth factor) receptor family. Accessed on 26/07/2016. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=320.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Catalytic receptors. Br J Pharmacol. 172: 5979-6023.