Target Validation Information
TTD ID	T14597
Target Name	Erbb2 tyrosine kinase receptor (HER2)
Type of Target	Successful
Drug Potency against Target	Lapatinib	Drug Info	Ki = 9.2 nM	[2]
	Merimepodib	Drug Info	Ki = 9.2 nM	[11]
	AEE-788	Drug Info	IC50 = 6 nM	[7]
	BIBW 2992	Drug Info	IC50 = 14 nM
	BMS-599626	Drug Info	IC50 = 32 nM	[9]
	CI-1033	Drug Info	IC50 = 19 nM	[8]
	CP-724714	Drug Info	IC50 = 3.8 nM	[8]
	HKI-272	Drug Info	Ki = 59 nM	[4]
	Lapatinib	Drug Info	Ki = 9.2 nM	[3]
	Pazopanib + Tyverb/Tykerb	Drug Info	pKi = 6.8	[6]
	TAK165	Drug Info	Ki = 6 nM	[5]
	(1-Benzyl-1H-indazol-5-yl)-quinazolin-4-yl-amine	Drug Info	IC50 = 10 nM	[1]
	(1-Benzyl-1H-indol-5-yl)-quinazolin-4-yl-amine	Drug Info	IC50 = 90 nM	[1]
Action against Disease Model	Trastuzumab	Drug Info	Overexpression of ErbB2 in breast cancer is associated with increased recurrence and worse prognosis. Acc uMulating evidences suggest that molecular targeted therapy is a promising anticancer strategy. In this study, we produced a novel anti-ErbB2 monoclonal antibody, 6G10, that recognized an epitope distinct from the trastuz uMab binding site. 6G10 induced aggregation of BT474 breast cancer cells and inhibited proliferation of various breast cancer cell lines including BT474. A growth inhibition assay showed that 6G10 had EC(50) values comparable to trastuz uMab, indicating that the drugs have a similar level of potency. Furthermore, intraperitoneal administration of 6G10 completely inhibited the growth of xenografted t uMors derived from BT474 and SK-BR-3 cells. These data suggested that 6G10 has great therapeutic potential and could be administered to patients alternatively, or synergistically, with trastuz uMab.	[10]
References
REF 1	Indazolylamino quinazolines and pyridopyrimidines as inhibitors of the EGFr and C-erbB-2. Bioorg Med Chem Lett. 2001 Jun 4;11(11):1401-5.
REF 2	Therapeutic opportunities from muscarinic receptor research. Trends Pharmacol Sci. 2001 Aug;22(8):409-14.
REF 3	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. 2001 Dec;1(2):85-94.
REF 4	Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase. Cancer Res. 2004 Jun 1;64(11):3958-65.
REF 5	Novel HER2 selective tyrosine kinase inhibitor, TAK-165, inhibits bladder, kidney and androgen-independent prostate cancer in vitro and in vivo. Int J Urol. 2006 May;13(5):587-92.
REF 6	Selective agents for serotonin2C (5-HT2C) receptor. Curr Top Med Chem. 2006;6(18):1927-70.
REF 7	Molecular design and clinical development of VEGFR kinase inhibitors. Curr Top Med Chem. 2007;7(14):1379-93.
REF 8	A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol. 2008 Jan;26(1):127-32.
REF 9	Recent advances in the development of multi-kinase inhibitors. Mini Rev Med Chem. 2008 Nov;8(13):1312-27.
REF 10	A novel mouse monoclonal antibody targeting ErbB2 suppresses breast cancer growth. Biochem Biophys Res Commun. 2009 Jul 3;384(3):329-33.
REF 11	Small molecule inhibitors of PKCTheta as potential antiinflammatory therapeutics. Curr Top Med Chem. 2009;9(7):640-54.

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