National Taiwan University

National Cheng-kung University

Yung Shin Pharmaceutical Ind. Co., Ltd.

Dcb-usa LLC

Chih-Hsin Tang

Wen-Mei Fu

Sheng-Chu Kuo

Che-Ming Teng

Fang-Yu Lee

Woei-Jer Chuang

Tur-Fu Huang

Wenya Huang

Rong-Sen Yang

Chiu-Yueh Chen

Disintegrin variants and pharmaceutical uses thereof are disclosed. The disintegrin variant includes an isolated polypeptide that has integrin &#x3b1;v&#x3b2;3 receptor-antagonist activity and substantially reduced integrin &#x3b1;llb&#x3b2;3 and/or &#x3b1;5&#x3b2;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 &#x3b1;llb&#x3b2;3 and/or &#x3b1;5&#x3b2;1 as compared to a wild-type disintegrin. The variant is useful for treatment and/or prevention of &#x3b1;v&#x3b2;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.

Disintegrin variants and their use in treating osteoporosis-induced bone loss and angiogenesis-related diseases

This invention features a method for enhancing bone growth or inhibiting bone resportion. The method includes administering to a subject in need thereof a compound of the following formula: A is H, R, or each of Ar, Ar, and Ar, independently, is phenyl, thienyl, furyl, or pyrrolyl; each of R, R, R, R, R, and R, independently, is H, halogen, R, C(O)OH, C(O)OR, C(O)SH, C(O)SR, C(O)NH, C(O)NHR, C(O)NRR', ROH, ROR&#x2032;, RSH, RSR&#x2032;, NHR, NRR&#x2032;, RNHR&#x2032;, or RNR&#x2032;R&#x2033;; or Rand Rtogether, Rand Rtogether, or Rand Rtogether are ORO; wherein each of R, R&#x2032;, and R&#x2033;, independently is C&#x2dc;Calkyl; and n is 1, 2, or 3.

Method of increasing bone density or treating osteoporosis

Growing community of inventors

Miaoli County, Taiwan

Chih-Hsin Tang