INDIANA UNIVERSITY RESEARCH AND TECHNOLOGY CORPORATION
发明人:
DIMARCHI, RICHARD D.,迪玛奇 理查D,迪瑪奇 理查D
申请号：
TW104121012
公开号：
TW201605469A
申请日:
2010.12.17
申请国别(地区):
TW
年份:
2016
代理人:
摘要：
Provided herein are glucagon analogs comprising a modified amino acid sequence of native human glucagon (SEQ ID NO: 2) that exhibit activity at the glucagon receptor, activity at the GLP-1 receptor, or activity at each of the glucagon recpeotr and the GLP-1 receptor. In some embodiments, the glucagon analog exhibits at least 100% or more of the activity of native glucagon at the glucagon receptor and/or at least 100% or more of the activity of native GLP-1 at the GLP-1 receptor. In some embodiments, the glucagon analog has an EC50 at the GLP-1 receptor which is within 50-fold or less than the EC50 at the glucagon receptor. In some embodiments, the glucagon analog has an EC50 at the GLP-1 receptor which is two- to ten-fold greater than the EC50 at the glucagon receptor. Related conjugates, dimers and multimers, and pharmaceutical compositions, and uses thereof, are further provided.本文中提供包含天然人類升糖素(SEQ ID NO:2)之經修飾胺基酸序列的升糖素類似物,其對升糖素受體展現活性,對GLP-1受體展現活性,或對升糖素受體及GLP-1受體之每一者展現活性。在一些實施例中,升糖素類似物對升糖素受體展現至少100%或100%以上之天然升糖素活性,及/或對GLP-1受體展現至少100%或100%以上之天然GLP-1活性。在一些實施例中,升糖素類似物對GLP-1受體之EC50為其對升糖素受體之EC50的50倍或50倍以下之內。在一些實施例中,升糖素類似物對GLP-1受體之EC50比其對升糖素受體之EC50高兩倍至十倍。進一步提供相關結合物、二聚體及多聚體,及醫藥組合物,及其用途。
