Disintegrin variants and pharmaceutical uses thereof are disclosed. The
disintegrin variant includes an isolated polypeptide that has integrin
.alpha.v.beta.3 receptor-antagonist activity and substantially reduced
integrin .alpha.llb.beta.3 and/or .alpha.5.beta.1 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 .alpha.llb.beta.3 and/or .alpha.5.beta.1 as
compared to a wild-type disintegrin. The variant is useful for treatment
and/or prevention of .alpha.v.beta.3 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.