ERBB2 binds TKIs

Stable Identifier
Reaction [binding]
Homo sapiens
Locations in the PathwayBrowser
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ERBB2 can bind to and be inhibited by the following tyrosine kinase inhibitors (TKIs):
lapatinib (Xia et al. 2002, Wood et al. 2004)
neratinib (Rabindran et al. 2004)
afatinib (Li et al. 2008)
AZ5104 (Hanker et al. 2017)
tesevatinib (Gendreau et al. 2007)
canertinib (Nelson and Fry 2001)
sapitinib (Hickinson et al. 2010)
CP-724714 (Jani et al. 2007)
AEE788 (Traxler et al. 2014). Tyrosine kinase inhibitors do not prevent ERBB2 heterodimerization, but intefere with its kinase activity.
The following tyrosine kinase inhibitors were shown to be especially effective against overexpressed ERBB2 and to inhibit kinase activity of ERBB2 homodimers:
afatinib (Rabindran et al. 2004)
neratinib (Rabindran et al. 2004)
lapatinib (Rabindran et al. 2004).
Literature References
PubMed ID Title Journal Year
15374980 A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells

Rusnak, DW, Wood, ER, Lackey, K, Yuan, D, Horne, E, Pennisi, C, Gilmer, TM, Dickerson, SH, Shewchuk, L, Alligood, KJ, Truesdale, AT, Hassell, A, Ellis, B, McDonald, OB

Cancer Res. 2004
17575237 Inhibition of the T790M gatekeeper mutant of the epidermal growth factor receptor by EXEL-7647

Jackman, L, Ventura, R, Shi, Y, De Costa, A, Zhang, W, Keast, P, Engell, K, Wang, J, Chen, J, Yu, P, Lutman, J, Bentzien, F, Laird, AD, Joly, AH, Meyer, SM, Martini, JF, Yakes, FM, Gendreau, SB, Jaeger, CT, Cancilla, B, Chu, F, Aftab, DT

Clin. Cancer Res. 2007
15256466 AEE788: a dual family epidermal growth factor receptor/ErbB2 and vascular endothelial growth factor receptor tyrosine kinase inhibitor with antitumor and antiangiogenic activity

Allegrini, PR, McSheehy, P, Mestan, J, Traxler, P, Fabbro, D, Caravatti, G, Brandt, R, Wartmann, M, Wood, J, Brueggen, J, Tang, C, Meyer, T, Lane, HA, Cozens, R, Grosios, K

Cancer Res. 2004
12214266 Anti-tumor activity of GW572016: a dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways

Spector, NL, Alligood, KJ, Rusnak, DW, Liu, LH, Keith, BR, Owens, G, Ma, H, Mullin, RJ, Xia, W

Oncogene 2002
17942920 Discovery and pharmacologic characterization of CP-724,714, a selective ErbB2 tyrosine kinase inhibitor

Finn, RS, Emerson, EO, Campbell, M, Steyn, SJ, Pustilnik, LR, Morris, J, Bhattacharya, SK, Kath, JC, Connell, RD, Rossi, AM, Floyd, E, Moyer, JD, Coleman, KG, Harriman, S, Wagner, L, Jani, JP, Ralston, S, Winter, SM, Currier, N, Rafidi, K

Cancer Res. 2007
20145185 AZD8931, an equipotent, reversible inhibitor of signaling by epidermal growth factor receptor, ERBB2 (HER2), and ERBB3: a unique agent for simultaneous ERBB receptor blockade in cancer

Ogilvie, D, Smith, P, Speake, G, Anderton, J, Beck, S, Wilkinson, RW, Vincent, J, Barlaam, B, Hickinson, DM, Klinowska, T, Marshall, G, Davenport, S, Callis, R, Trigwell, C, Grosios, K, Mills, E

Clin. Cancer Res. 2010
28274957 An Acquired HER2T798I Gatekeeper Mutation Induces Resistance to Neratinib in a Patient with HER2 Mutant-Driven Breast Cancer

Hyman, DM, Solit, DB, Nagy, R, Sheehan, JH, Sliwoski, GR, Berger, MF, He, J, Lalani, AS, Brewer, MR, Miller, V, Cross, D, Cutler, RE, Hanker, AB, Lanman, R, Arteaga, CL, Koch, JP, Lovly, CM, Meiler, J

Cancer Discov 2017
18408761 BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models

Meyerson, M, Li, D, Wong, KK, Ambrogio, L, Chirieac, LR, Takahashi, M, Shimamura, T, Shapiro, GI, Baum, A, Rettig, WJ, Padera, RF, Himmelsbach, F, Solca, F, Kubo, S, Greulich, H

Oncogene 2008
11278435 Akt, MAPK (Erk1/2), and p38 act in concert to promote apoptosis in response to ErbB receptor family inhibition

Nelson, JM, Fry, DW

J. Biol. Chem. 2001
15173008 Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase

Johnson, BD, Overbeek, E, Baxter, M, Wissner, A, Shen, R, Wang, YF, Tsou, HR, Floyd, MB, Discafani, CM, Rabindran, SK, Nilakantan, R, Rosfjord, EC, Golas, J, Reich, MF, Shi, X, Hallett, WA

Cancer Res 2004
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