摘要 |
Disintegrin variants and pharmaceutical uses thereof are disclosed. The disintegrin variant includes an isolated polypeptide that has integrin ±v²3 receptor-antagonist activity and substantially reduced integrin ±IIb²3 and/or ±5²1 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 ±IIb²3 and/or ±5²1 as compared to a wild-type disintegrin. The variant is useful for treatment and/or prevention of ±v²3 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. |
申请人 |
NATIONAL TAIWAN UNIVERSITY;DCB-USA LLC |
发明人 |
CHUANG, WOEI-JER;FU, WEN-MEI;HUANG, TUR-FU;HUANG, WENYA;TANG, CHIH-HSIN;CHEN, CHIU-YUEH |