| abstract |
The present invention provides a cyclic polypeptide of formula I or an amide, ester or salt thereof, or a bioconjugate thereof, wherein X1, X3, X4, X7, X8, X9, X10, X11, X12 and X13 are as defined herein. The polypeptide is an agonist of the APJ receptor. The present invention also relates to methods for preparing polypeptides of the present invention or bioconjugates thereof, and therapeutic uses thereof, such as the treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular disease, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes mellitus (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accident, transient ischemic attack, traumatic brain injury, amyotrophic lateral sclerosis, burns (including sunburn), and preeclampsia. The present invention also provides combinations of pharmacologically active agents and pharmaceutical compositions. X1-R-X3-X4-L-S-X7-X8-X9-X10-X11-X12-X13? ? (I). |