Disintegrin variants and pharmaceutical uses thereof are disclosed. The disintegrinvariant includes an isolated polypeptide that has integrin avß3 receptor-antagonistactivity and substantially reduced integrin aIIbß3 and/or a5ß1receptor-blocking activity as compared to a wild-type disintegrin. The variantis encoded by a modified disintegrin nucleotide sequence that encodes a modifiedamino acid sequence, resulting in a polypeptide having substantially reducedaffinity to integrin aIIbß3 and/or a5ß1 as compared to a wild-typedisintegrin. The variant is useful for treatment and/or prevention of avß3integrin-associated diseases in a mammal, which include osteoporosis, bonetumor or cancer growth, angiogenesis-related tumor growth and metastasis,tumor metastasis in bone, malignancy-induced hypercalcemia, angiogenesis-relatedeye diseases, Paget's disease, rheumatic arthritis, and osteoarthritis.The angiogenesis-related eye diseases include age-related macular degeneration,diabetic retinopathy, corneal neovascularizing diseases, ischaemia-inducedneovascularizing retinopathy, high myopia, and retinopathy of prematurity.
