Exendin agonist compounds
View Patent ↗The present invention relates to novel exendin agonist compounds useful in treatment of Type I and II diabetes, and useful in lowering plasma glucose levels, reducing body weight, and delaying and/or slowing gastric emptying.
1. An isolated peptide compound according to SEQ ID NO:4 and having the formula:
His Xaa 2 Xaa 3 Gly Thr Phe Thr Xaa 8 Asp Xaa 10 Ser Lys Gln Xaa 14 Glu Glu Glu Ala Val Arg Leu Xaa 22 Xaa 23 Glu Xaa 25 Leu Lys Xaa 28 Gly Gly Pro Ser Ser Gly Ala Pro Pro Pro-Z
Wherein Xaa 2 is Ser, Gly or Thr,
Xaa 3 is Asp or Glu
Xaa 8 is Ala, Ser, or Thr,
Xaa 10 is Leu, Ile, Val, pentylglycine or Met,
Xaa 14 is Ala, Leu, Ile, pentylglycine, Val,
Xaa 22 is Phe, Tyr or naphthylalanine,
Xaa 23 is Ile, Val, Leu, pentylglycine, tert-butylglycine or Met,
Xaa 25 is Ala, Trp, Phe, Tyr or naphthylalanine,
Xaa 28 is Ala or Asn, and
Z is —OH or NH 2 ; or a
pharmaceutically acceptable salt thereof.
2. The isolated peptide compound or salt thereof of claim 1 , wherein Xaa 2 is Ser.
3. The isolated peptide compound or salt thereof of claim 1 , wherein Xaa 2 is Gly.
4. The isolated peptide compound or salt thereof of claim 1 , wherein Xaa 3 is Asp.
5. The isolated peptide compound or salt thereof of claim 1 , wherein Xaa 14 is Leu.
6. The isolated peptide compound or salt thereof of claim 1 , wherein Xaa 25 is Phe.
7. The isolated peptide compound or salt thereof of claim 1 , wherein Xaa 28 is Ala.
8. The isolated peptide compound or salt thereof of claim 1 , wherein Z is NH 2 .
9. An isolated peptide compound according to SEQ ID NO:4 and having the formula:
His Xaa 2 Xaa 3 Gly Thr Phe Thr Ser Asp Leu Ser Lys Gln Met Glu Glu Glu Ala Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly Gly Pro Ser Ser Gly Ala Pro Pro Pro-Z
Wherein
Xaa 2 is Ala or Thr, Xaa 3 is Glu or Asp; and Z is —OH or NH 2 , wherein said peptide compound is an exendin agonist; or a pharmaceutically acceptable salt thereof.
10. The isolated peptide compound or salt thereof of claim 9 , wherein Xaa 2 is Ser.
11. The isolated peptide compound or salt thereof of claim 9 , wherein Xaa 3 is Asp.
12. The isolated peptide compound or salt thereof of claim 9 , wherein Z is NH 2 .
13. A method for the treatment of diabetes mellitus comprising the administration, to a subject in need thereof, of a therapeutically effective amount of a compound or salt thereof according to claim 1 .
14. The method of claim 13 further comprising the administration of a therapeutically effective amount of an insulin.
15. A method for the treatment of diabetes mellitus comprising the administration, to a subject in need thereof, of a therapeutically effective amount of a compound or a salt thereof according to claim 9 .
16. The method of claim 15 further comprising the administration of a therapeutically effective amount of an insulin.