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glp1/gip dual agonist or glp1/gip/glucagon triple agonist

A technology for hyperglycemia and body weight, applied in the direction of glucagon, hormone peptides, anti-toxins, etc., can solve the chemical instability of exendin-4 and other problems

Inactive Publication Date: 2018-11-20
SANOFI SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0010] But exendin-4 is chemically unstable due to the oxidation of methionine at position 14 (Hargrove DM et al., Regul. Pept., 141:113-9, 2007), and the methionine at position 28. Asparagine deamination and isomerization (WO 2004 / 035623)

Method used

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  • glp1/gip dual agonist or glp1/gip/glucagon triple agonist
  • glp1/gip dual agonist or glp1/gip/glucagon triple agonist
  • glp1/gip dual agonist or glp1/gip/glucagon triple agonist

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[0353] definition

[0354] The amino acid sequences of the present invention contain the conventional one-letter or three-letter codes for naturally occurring amino acids, as well as the generally accepted three-letter codes for other amino acids, such as Aib (alpha-aminoisobutyric acid), Orn (ornithine ), Dab (2,4-diaminobutyric acid), Dap (2,3-diaminopropionic acid), Nle (norleucine), GABA (γ-aminobutyric acid) or Ahx (ε-aminocaproic acid )

[0355] In addition, the following codes were used for the amino acids shown in Table 4.

[0356] Table 4:

[0357]

[0358] The term "natural exendin-4" means a compound having the sequence HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH 2 Native Exendin-4 of (SEQ ID NO: 1).

[0359] The present invention provides a peptide compound as defined above.

[0360] The peptidic compounds of the present invention comprise a linear backbone of aminocarboxylic acids linked by peptide bonds, ie, carboxamide bonds. Preferably, the aminocarboxy...

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Abstract

The present invention relates to exendin-4 derivatives and their use in medicine, for example in the treatment of disorders of the metabolic syndrome, including diabetes and obesity, and in reducing excess food intake.

Description

[0001] manual field of invention [0002] The present invention relates to exendin-4 (exendin-4) peptide analogs, which activate glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, and optionally Activation of glucagon receptors (GCG), and their medicinal use, for example in the treatment of disorders of the metabolic syndrome including diabetes and obesity and in reducing excess food intake. Background of the invention [0003] Exendin-4 is a 39 amino acid peptide produced by the Gila monster (Heloderma suspectum) (Eng J. et al., J. Biol. Chem. , 267:7402-05, 1992). Exendin-4 is an activator of the glucagon-like peptide-1 (GLP-1) receptor, however it shows only low activation of the GLP receptor and does not activate the glucagon receptor. body (see Table 1). [0004] Table 1: Potency of exendin-4 at increasing concentrations on human GLP-1, GIP and glucagon receptors (expressed in pM), and cAMP formed measured as described i...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/26C07K14/605
CPCA61K38/00A61K38/2264C07K14/605A61K38/26A61K45/06A61K38/28A61P1/00A61P1/16A61P25/00A61P25/28A61P25/30A61P3/00A61P3/04A61P3/06A61P3/08A61P39/02A61P43/00A61P9/00A61P9/10A61P9/12A61P3/10Y02A50/30A61K2300/00A61K9/0019
Inventor T·哈克M·瓦格纳B·亨克尔S·斯滕格林A·埃弗斯M·洛伦茨K·洛伦茨
Owner SANOFI SA
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