| abstract |
The present invention provides a cyclic polypeptide of the formula I': X1-R-X3-X4-L-S-X7-X8-X9-X10-X11-X12-X13 InOr a guanamine, ester or salt thereof, or a biological combination 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 invention also relates to a method for the manufacture of a polypeptide of the invention or a bioconjugate thereof, and to its therapeutic use, such as for the treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrosis Quiver, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular disease, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, Diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accident, transient ischemic attack, traumatic brain injury, amyotrophic lateral sclerosis, burns (including sunburn), and pre-eclampsia. The invention further provides combinations and pharmaceutical compositions of pharmacologically active agents. |