Disintegrin variants and pharmaceutical composition thereof are disclosed. The disintegrin variant includes an isolated polypeptide that has integrin αvβ3 receptor-antagonist activity and substantially reduced integrin αIIbβ3 and/or α5β1 receptor-blocking activity as compared to a wild-type disintegrin. The variant is encoded by a modified disintegrin nucleotide sequence that encodes a modified amino acid sequence, resulting in a polypeptide having substantially reduced affinity to integrin αIIbβ3 and/or α5β1 as compared to a wild-type disintegrin. The variant is useful for treatment and/or prevention of αvβ3 integrin-associated diseases in a mammal, which include osteoporosis, bone tumor or cancer growth, angiogenesis-related tumor growth and metastasis, tumor metastasis in bone, malignancy-induced hypercalcemia, angiogenesis-related eye diseases, Paget’s disease, rheumatic arthritis, and osteoarthritis. The angiogenesis-related eye diseases include age-related macular degeneration, diabetic retinopathy, corneal neovascularizing diseases, ischaemia-induced neovascularizing retinopathy, high myopia, and retinopathy of prematurity.一種去整合蛋白變異體及其醫藥組成物。去整合蛋白變異體包含一分離之單離多胜肽，其具有整合蛋白αvβ3受體拮抗活性，且其整合蛋白αIIbβ3和/或α5β1受體阻斷活性明顯小於野生型去整合蛋白之受體阻斷活性。變異體係由改造去整合蛋白胺基酸序列所編碼的核苷酸序列而產生的多胜肽，相較於一野生型去整合蛋白，對於整合蛋白αIIbβ3和/或α5β1之親和力顯著減低。該變異體可有效治療和/或預防哺乳類動物與αvβ3整合蛋白相關之疾病。上述疾病包含骨質疏鬆症、骨腫瘤或骨癌生長、與血管生成相關之腫瘤生長及癌細胞轉移、骨骼中之腫癌轉移、惡性腫瘤引起之高血鈣症、與血管生成相關之眼部疾病、派傑氏症(Paget’s disease)、風濕性關節炎及退化性關節炎。與血管生成相關之眼部疾病包含老年性黃斑病變、糖尿病視網膜病變、角膜神經血管增生病變、局部缺血導致之神經血管增生視網膜病變、高度近視及早熟性視網膜病變。
