Target Validation Information
TTD ID	T21960
Target Name	Angiopoietin-2 (ANGPT2)
Type of Target	Successful
Action against Disease Model	AMG 386	Drug Info	A VEGF-driven rat corneal angiogenesis model was used to establish a direct non-t uMorigenic anti-neovascular effect of AMG 386, with Ang2 expression in the nascent vasculature demonstrated by in situ hybridization. Exposure to AMG 386 led to dose-dependent inhibition of VEGF-mediated corneal angiogenesis. Reversible epiphyseal plate thickening was observed in rats treated with high doses of AMG 386 (75 and 200 mg/kg twice weekly for 2 weeks), a characteristic pharmacological sequela of anti-angiogenic therapy in growing rats that is not expected to occur in adults in whom endochondrial bone formation has ceased. AMG 386 was shown to neutralize Ang2-Tie2 and Ang1-Tie2 interactions with IC50 values of 23 and 900 pM, respectively. In nude mice bearing subcutaneous Colo205 h uMan colorectal t uMor xenografts, exposure to AMG 386 inhibited t uMor growth when administered either 3 or 28 days following t uMor cell injection at an optimal dose of 0.6 mg/kg twice weekly.	[1]
References
REF 1	AMG 386: profile of a novel angiopoietin antagonist in patients with ovarian cancer. Expert Opin Investig Drugs. 2011 Feb;20(2):297-304.

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