| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T14597 | ||||
| Target Name | Receptor protein-tyrosine kinase erbB-2 | ||||
| Target Type | Successful |
||||
| Drug Potency against Target | Lapatinib | Drug Info | Ki = 9.2 nM | [1] | |
| CI-1033 | Drug Info | IC50 = 19 nM | [2] | ||
| Pazopanib + Tyverb/Tykerb | Drug Info | pKi = 6.8 | [3] | ||
| HKI-272 | Drug Info | Ki = 59 nM | [4] | ||
| Lapatinib | Drug Info | Ki = 9.2 nM | [5] | ||
| CP-724714 | Drug Info | IC50 = 3.8 nM | [2] | ||
| BIBW 2992 | Drug Info | IC50 = 14 nM | |||
| TAK165 | Drug Info | Ki = 6 nM | [6] | ||
| Tyverb/Tykerb | Drug Info | Ki = 9.2 nM | [7] | ||
| (1-Benzyl-1H-indazol-5-yl)-quinazolin-4-yl-amine | Drug Info | IC50 = 10 nM | [8] | ||
| (1-Benzyl-1H-indol-5-yl)-quinazolin-4-yl-amine | Drug Info | IC50 = 90 nM | [8] | ||
| BMS-599626 | Drug Info | IC50 = 32 nM | [9] | ||
| AEE-788 | Drug Info | IC50 = 6 nM | [10] | ||
| Action against Disease Model | Trastuzumab | 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. | [11] | Drug Info | |
| References | |||||
| REF 1 | Therapeutic opportunities from muscarinic receptor research. Trends Pharmacol Sci. 2001 Aug;22(8):409-14. | ||||
| REF 2 | A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol. 2008 Jan;26(1):127-32. doi: 10.1038/nbt1358. | ||||
| REF 3 | Selective agents for serotonin2C (5-HT2C) receptor. Curr Top Med Chem. 2006;6(18):1927-70. | ||||
| 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 | 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 6 | 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 7 | Small molecule inhibitors of PKCTheta as potential antiinflammatory therapeutics. Curr Top Med Chem. 2009;9(7):640-54. | ||||
| REF 8 | Bioorg Med Chem Lett. 2001 Jun 4;11(11):1401-5.Indazolylamino quinazolines and pyridopyrimidines as inhibitors of the EGFr and C-erbB-2. | ||||
| REF 9 | Recent advances in the development of multi-kinase inhibitors. Mini Rev Med Chem. 2008 Nov;8(13):1312-27. | ||||
| REF 10 | Molecular design and clinical development of VEGFR kinase inhibitors. Curr Top Med Chem. 2007;7(14):1379-93. | ||||
| REF 11 | A novel mouse monoclonal antibody targeting ErbB2 suppresses breast cancer growth. Biochem Biophys Res Commun. 2009 Jul 3;384(3):329-33. doi: 10.1016/j.bbrc.2009.04.118. Epub 2009 May 4. | ||||
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