ES2495741T3 - Compuestos de GLP-1 - Google Patents

Compuestos de GLP-1 Download PDF

Info

Publication number
ES2495741T3
ES2495741T3 ES07761068.1T ES07761068T ES2495741T3 ES 2495741 T3 ES2495741 T3 ES 2495741T3 ES 07761068 T ES07761068 T ES 07761068T ES 2495741 T3 ES2495741 T3 ES 2495741T3
Authority
ES
Spain
Prior art keywords
amide
lvkgr
lys
xaa
hgegt ftsdv
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
ES07761068.1T
Other languages
English (en)
Inventor
Colin Victor Gegg, Jr.
Leslie Phillip MIRANDA
Katherine Ann WINTERS
Murielle Veniant-Ellison
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Amgen Inc
Original Assignee
Amgen Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Amgen Inc filed Critical Amgen Inc
Application granted granted Critical
Publication of ES2495741T3 publication Critical patent/ES2495741T3/es
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575—Hormones
    • C07K14/605—Glucagons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Zoology (AREA)
  • Neurology (AREA)
  • Emergency Medicine (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Vascular Medicine (AREA)
  • Anesthesiology (AREA)
  • Pain & Pain Management (AREA)
  • Urology & Nephrology (AREA)

Abstract

Un compuesto de GLP-1 que comprende un análogo de GLP-1 que comprende la secuencia de aminoácidos de fórmula I (SEC ID Nº: 5): Xaa7-Gly-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-Xaa17-Xaa18-Xaa19-Xaa20-Xaa21-Xaa22-Cys-Xaa24- Xaa25-Xaa26-Xaa27Xaa28-Xaa29-Xaa30-Xaa31-Xaa32-Xaa33-Xaa34-Gly-Xaa36-Xaa37-Ser-Ser-Gly-Ala-Pro-Pro-Pro- Ser-C(O)-R1 en la que R1 es OR2 o NR2R3; R2 y R3 son independientemente hidrógeno o alquilo (C1-C8); Xaa en la posición 7 es: L-histidina, D-histidina, desamino-histidina, 2-amino-histidina, 3-hidroxi-histidina, homohistidina, β-fluorometil-histidina o β-metil-histidina; Xaa en la posición 9 es Glu, Asp o Lys; Xaa en la posición 10 es Gly o His; Xaa en la posición 11 es Thr, Ala, Gly, Ser, Leu, Ile, Val, Glu, Asp o Lys; Xaa en la posición 12 es: His, Trp, Phe o Tyr; Xaa en la posición 13 es Thr o Gly; Xaa en la posición 14 es Ser, Ala, Gly, Thr, Leu, Ile, Val, Glu, Asp o Lys; Xaa en la posición 15 es Asp o Glu; Xaa en la posición 16 es Val, Ala, Gly, Ser, Thr, Leu, Ile, Tyr, Glu, Asp, Trp o Lys; Xaa en la posición 17 es Ser, Ala, Gly, Thr, Leu, Ile, Val, Glu, Asp o Lys; Xaa en la posición 18 es Ser, Ala, Gly, Thr, Leu, Ile, Val, Glu, Asp, Trp, Tyr, Lys, homolisina, ornitina, 4-carboxifenilalanina, ácido beta-glutámico, ácido beta-homoglutámico o ácido homoglutámico; Xaa en la posición 19 es Tyr, Phe, Trp, Glu, Asp, Gln, Lys, homolisina, ornitina, 4-carboxi-fenilalanina, ácido beta-glutámico, ácido beta-homoglutámico o ácido homoglutámico; Xaa en la posición 20 es Leu, Ala, Gly, Ser, Thr, Ile, Val, Glu, Asp, Met, Trp, Tyr, Lys, homolisina, ornitina, 4- carboxi-fenilalanina, ácido beta-glutámico o ácido homoglutámico; Xaa en la posición 21 es Glu, Asp, Lys, homolisina, ornitina, 4-carboxi-fenilalanina, ácido beta-glutámico, ácido beta-homoglutámico o ácido homoglutámico; Xaa en la posición 22 es Gly, Ala, Ser, Thr, Leu, Ile, Val, Glu, Asp, Lys, homolisina, ornitina, 4-carboxifenilalanina, ácido beta-glutámico, ácido beta-homoglutámico o ácido homoglutámico; Xaa en la posición 24 es Ala, Gly, Ser, Thr, Leu, Ile, Val, Arg, Glu, Asp, Lys, homolisina, ornitina, 4-carboxifenilalanina, ácido beta-glutámico, ácido beta-homoglutámico o ácido homoglutámico; Xaa en la posición 25 es Ala, Gly, Ser, Thr, Leu, Ile, Val, Glu, Asp, Lys, homolisina, ornitina, 4-carboxifenilalanina, ácido beta-glutámico, ácido beta-homoglutámico o ácido homoglutámico; Xaa en la posición 26 es Lys, homolisina, Arg, Gln, Glu, Asp, His, ornitina, 4-carboxi-fenilalanina, ácido beta40 glutámico o ácido homoglutámico; Xaa en la posición 27 es Leu, Glu, Asp, Lys, homolisina, ornitina, 4-carboxi-fenilalanina, ácido beta-glutámico, ácido beta-homoglutámico o ácido homoglutámico; Xaa en la posición 28 es Phe, Trp, Asp, Glu, Lys, homolisina, ornitina, 4-carboxi-fenilalanina, ácido betaglutámico, ácido beta-homoglutámico o ácido homoglutámico; Xaa en la posición 29 es Ile, Leu, Val, Ala, Phe, Asp, Glu, Lys, homolisina, ornitina, 4-carboxi-fenilalanina, ácido beta-glutámico, ácido beta-homoglutámico o ácido homoglutámico; Xaa en la posición 30 es Ala, Gly, Ser, Thr, Leu, Ile, Val, Glu, Asp, Lys, homolisina, ornitina, 4-carboxifenilalanina, ácido beta-glutámico, ácido beta-homoglutámico o ácido homoglutámico; Xaa en la posición 31 es Trp, Phe, Tyr, Glu, Asp o Lys; Xaa en la posición 32 es Leu, Gly, Ala, Ser, Thr, Ile, Val, Glu, Asp o Lys; Xaa33 es: Val o Lys; Xaa34 es: Lys o Asn; Xaa36 es: Arg o Gly; Xaa37 es: Gly o Pro; en la que el compuesto tiene una actividad de GLP-1, en la que dicha actividad de GLP-1 es actividad insulinotrópica.

Description

imagen1
imagen2
imagen3
imagen4
imagen5
imagen6
imagen7
imagen8
imagen9
imagen10
imagen11
imagen12
imagen13
imagen14
imagen15
imagen16
imagen17
imagen18
imagen19
imagen20
E07761068
25-08-2014
Análogo de GLP-1
Ref. interna SEC ID Nº:
HGEGT FTSDV SSYLE GCAAK EFIAW LVKGR GSSGA PPPS
cgGLP-12, 14 7
HGEGT FTSDV SSYLE GCAAK EFIAW LKNGG PSSGA PPPS
cgGLP-13, 15 8
XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XCSGG
Fórmula II 9
HGEGT FTSDV SSYLE GQAAK EFIAW LVKGR GCSG
cgGLP-4-6, 8, 10, 16 10
HZEGT FTSDV SSYLE GQAAK EFIAW LVKGR GCSGG
cgGLP-17 11
H[bAla]EGT FTSDV SSYLE GQAAK EFIAW LVKGR GCSGG
cgGLP-18 12
XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX GXXXX
Fórmula III 13
HAEGT FTSDV SSYLE ZQAAK EFIAW LVKGR-amida
14
HGEGT FTSDV SSYLE ZQAAK EFIAW LVKGR G-amida
15
HGEGT FTSDV SSYLE ZQAAK EFIAW LVKGR GC
16
HGEGT FTSDV SSYLE ZQAAK EFIAW LVKGR GC-amida
cgGLP-23 17
HGEGT FTSDV SSYLE ZQAAK EFIAW LVKGR GCA-amida
cgGLP30 y mgGLP 20 18
HGEGT FTSDV SSYLE ZQAAK EFIAW LVKGR GCG
19
HGEGT FTSDV SSYLE ZQAAK EFIAW LVKGR GCG-amida
mgGLP-16 20
HGEGT FTSDV SSYLE ZQAAK EFIAW LVKGR GCSG
cgGLP-19 21
HGEGT FTSDV SSYLE ZQAAK EFIAW LVKGR GCSG-amida
cgGLP-24-29, mgGLP22, mgGLP-33, mgGLP-27 22
HGEGT FTSDV SSYLE ZQAAK EFIAW LVKGR GCSGG
23
HGEGT FTSDV SSYLE ZQAAK EFIAW LVKGR GCSGG-amida
mgGLP-15 24
HZEGT FTSDV SSYLE ZQAAK EFIAW LVKGR GCSG
cgGLP-20 25
HZEGT FTSDV SSYLE ZQAAK EFIAW LVKGR GCSGG
26
HZEGT FTSDV SSYLE ZQAAK EFIAW LVKGR GGC
cgGLP-22 27
HGEGT FTSDV SSYLE [Aad]QAAK EFIAW LVKGR GCSG
cgGLP-21 28
Fórmula IV
29
HGEGT FTSDV SSYLE EQAAKEFIAW LVKGR G-amida
cicloE22-R26 (mgGLP-24) 30
HGEGT FTSDV SSYLE EQAAKEFIAW LVKGR GCA-amida
31
HGEGT FTSDV SSYLE EQAAKEFIAW LVKGR GCSG-amida
cicloE22-K26/CSG 32
HGEGT FTSDV SEYLE KQAAK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [18-22] -Lys/Orn 38 33
HGEGT FTSDV SSELE GKAAK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [19-23] -Lys/Orn 38 34
HGEGT FTSDV SSYEE GQKAK EFIAW LVKGR G[K/O/C]-amida
[GlyB]GLP1(7-37) ciclo[Glu14-Lys18]38 35
HGEGT FTSDV SSYLE GQAKK EFIAW LVKGR G[K/O/C]-amida
[Gly8]GLP1(7-37) cyc[Glu15-Lys19] 36
HGEGT FTSDV SSYLE EQAAKEFIAW LVKGR G[K/O/C]-amida
G8 ciclo[22-26] -Lys/Orn 38 37
HGEGT FTSDV SSYLE GEAAKKFIAW LVKGR G[K/O/C]-amida
[Gly8]GLP1(7-37) ciclo[Glu17-Lys21] 38
HGEGT FTSDV SSYLE GQEAK EKIAW LVKGR G[K/O/C]-amida
[Gly8]GLP1(7-37) ciclo[Glu18-Lys22] 39
HGEGT FTSDV SSYLE GQAEK EFKAW LVKGR G[K/O/C]-amida
G8 ciclo [25-29] -Lys/Orn 38 40
HGEGT FTSDV SSYLE GQAAEEFIKW LVKGR G[K/O/C)-amida
G8 ciclo [26-30] -Lys/Orn 38 41
HGEGT FTSDV SSYLE GQAAKEFIAW LVKGR G[K/O/C]-amida
[Gly8]ciclo[21-26] GLP1(737)-amida 42
HGEGT FTSDV SSYLE JQAAKEFIAW LVKGR G-amida
cicloJ22-K26 43
HGEGT FTSDV SSYLE JQAAKEFIAW LVKGR GCA-amida
cicloJ22-K26 44
HGEGT FTSDV SSYLE JQAAKEFIAW LVKGR GCSG-amida
cicloJ22-K26/CSG 45
HGEGT FTSDV SJYLE KQAAK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [18-22] -Lys/Orn/Cys 38 46
HGEGT FTSDV SSJLE GKAAK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [19-23] -Lys/Orn/Cys 38 47
HGEGT FTSDV SSYJE GQKAK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [20-24] -Lys/Orn/Cys 38 48
HGEGT FTSDV SSYLJ GQAKK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [21-25] -Lys/Orn/Cys 38 49
HGEGT FTSDV SSYLE JQAAKEFIAW LVKGR G[K/O/C]-amida
G8 ciclo [22-26] -Lys/Orn/Cys 38 50
22
E07761068
25-08-2014
Análogo de GLP-1
Ref. interna SEC ID Nº:
HGEGT FTSDV SSYLE GJAAKKFIAW LVKGR G[K/O/C]-amida
G8 ciclo [23-27] -Lys/Orn/Cys 38 51
HGEGT FTSDV SSYLE GQJAK EKIAW LVKGR G[K/O/C]-amida
G8 ciclo [24-28] -Lys/Orn/Cys 38 52
HGEGT FTSDV SSYLE GQAJK EFKAW LVKGR G[K/O/C]-amida
G8 ciclo [25-29] -Lys/Orn/Cys 38 53
HGEGT FTSDV SSYLE GQAAJEFIKW LVKGR G[K/O/C]-amida
G8 ciclo [26-30] -Lys/Orn/Cys 38 54
HGEGT FTSDV SSYLJ GQAAKEFIAW LVKGR G[K/O/C]-amida
G8 ciclo [21-26] -Lys/Orn/Cys 38 55
HGEGT FTSDV SSYLE KQAAJEFIAW LVKGR G-amida
56
HGEGT FTSDV SSYLE KQAAJEFIAW LVKGR GCA-amida
57
HGEGT FTSDV SSYLE KQAAJEFIAW LVKGR GCSG-amida
58
HGEGT FTSDV SKYLE JQAAK EFIAW LVKGR G[K/O/C]-amida
59
HGEGT FTSDV SSKLE GJAAK EFIAW LVKGR G[K/O/C]-amida
60
HGEGT FTSDV SSYKE GQJAK EFIAW LVKGR G[K/O/C]-amida
61
HGEGT FTSDV SSYLK GQAJK EFIAW LVKGR G[K/O/C]-amida
62
HGEGT FTSDV SSYLE KQAAJEFIAW LVKGR G[K/O/C]-amida
63
HGEGT FTSDV SSYLE GKAAKJFIAW LVKGR G[K/O/C]-amida
64
HGEGT FTSDV SSYLE GQKAK EJIAW LVKGR G[K/O/C]-amida
65
HGEGT FTSDV SSYLE GQAKK EFJAW LVKGR G[K/O/C]-amida
66
HGEGT FTSDV SSYLE GQAAKEFIJW LVKGR G[K/O/C]-amida
67
HGEGT FTSDV SSYLK GQAAJEFIAW LVKGR G[K/O/C]-amida
68
HGEGT FTSDV SSYLE EQAAOEFIAW LVKGR G-amida
cicloE22-026 69
HGEGT FTSDV SSYLE EQAAOEFIAW LVKGR GCA-amida
cicloE22-026 70
HGEGT FTSDV SSYLE EQAAOEFIAW LVKGR GCSG-amida
cicloE22-026/CSG 71
HGEGT FTSDV SEYLE OQAAK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [18-22] -Lys/Orn/Cys 38 72
HGEGT FTSDV SSELE GOAAK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [19-23] -Lys/Orn/Cys 38 73
HGEGT FTSDV SSYEE GQOAK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [20-24] -Lys/Orn/Cys 38 74
HGEGT FTSDV SSYLE GQAOK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [21-25] -Lys/Orn/Cys 38 75
HGEGT FTSDV SSYLE EQAAOEFIAW LVKGR G[K/O/C]-amida
G8 ciclo [22-26] -Lys/Orn/Cys 38 76
HGEGT FTSDV SSYLE GEAAKOFIAW LVKGR G[K/O/C]-amida
G8 ciclo [23-27] -Lys/Orn/Cys 38 77
HGEGT FTSDV SSYLE GQEAK EOIAW LVKGR G[K/O/C]-amida
G8 ciclo [24-28] -Lys/Orn/Cys 38 78
HGEGT FTSDV SSYLE GQAEK EFOAW LVKGR G[K/O/C]-amida
G8 ciclo [25-29] -Lys/Orn/Cys 38 79
HGEGT FTSDV SSYLE GQAAEEFIOW LVKGR G[K/O/C]-amida
G8 ciclo [26-30] -Lys/Orn/Cys 38 80
HGEGT FTSDV SSYLE GQAAOEFIAW LVKGR G[K/O/C]-amida
G8 ciclo [21-26] -Lys/Orn/Cys 38 81
HGEGT FTSDV SSYLE OQAAEEFIAW LVKGR G-amida
82
HGEGT FTSDV SSYLE OQAAEEFIAW LVKGR GCA-amida
83
HGEGT FTSDV SSYLE OQAAEEFIAW LVKGR GCSG-amida
84
HGEGT FTSDV SOYLE EQAAK EFIAW LVKGR G[K/O/C]-amida
85
HGEGT FTSDV SSOLE GEAAK EFIAW LVKGR G[K/O/C]-amida
86
HGEGT FTSDV SSYOE GQEAK EFIAW LVKGR G[K/O/C]-amida
87
HGEGT FTSDV SSYLO GQAEK EFIAW LVKGR G[K/O/C]-amida
88
HGEGT FTSDV SSYLE OQAAEEFIAW LVKGR G[K/O/C]-amida
89
HGEGT FTSDV SSYLE GOAAKEFIAW LVKGR G[K/O/C]-amida
90
HGEGT FTSDV SSYLE GQOAK EEIAW LVKGR G[K/O/C]-amida
91
HGEGT FTSDV SSYLE GQAOK EFEAW LVKGR G[K/O/C]-amida
92
HGEGT FTSDV SSYLE GQAAOEFIEW LVKGR G[K/O/C]-amida
93
HGEGT FTSDV SSYLO GQAAEEFIAW LVKGR G[K/O/C]-amida
94
HGEGT FTSDV SSYLE DQAAOEFIAW LVKGR G-amida
cicloD22-K26 95
HGEGT FTSDV SSYLE DQAAOEFIAW LVKGR GCA-amida
cicloD22-K26 96
23
E07761068
25-08-2014
Análogo de GLP-1
Ref. interna SEC ID Nº:
HGEGT FTSDV SSYLE DQAAOEFIAW LVKGR GCSG-amida
cicloD22-K26/CSG 97
HGEGT FTSDV SDYLE OQAAK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [18-22] -Lys/Orn/Cys 38 98
HGEGT FTSDV SSDLE GOAAK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [19-23] -Lys/Orn/Cys 38 99
HGEGT FTSDV SSYDE GQOAK EFIAW LVKGR G[K/O/C]-amida
GB ciclo [20-24] -Lys/Orn/Cys 38 100
HGEGT FTSDV SSYLD GQAOK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [21-25] -Lys/Orn/Cys 38 101
HGEGT FTSDV SSYLE DQAAOEFIAW LVKGR G[K/O/C]-amida
G8 ciclo [22-26] -Lys/Orn/Cys 38 102
HGEGT FTSDV SSYLE GDAAKOFIAW LVKGR G[K/O/C]-amida
G8 ciclo [23-27] -Lys/Orn/Cys 38 103
HGEGT FTSDV SSYLE GQDAK EOIAW LVKGR G[K/O/C]-amida
G8 ciclo [24-28] -Lys/Orn/Cys 38 104
HGEGT FTSDV SSYLE GQADK EFOAW LVKGR G[K/O/C]-amida
G8 ciclo [25-29] -Lys/Orn/Cys 38 105
HGEGT FTSDV SSYLE GQAADEFIOW LVKGR G[K/O/C]-amida
G8 ciclo [26-30] -Lys/Orn/Cys 38 106
HGEGT FTSDV SSYLE OQAADEFIAW LVKGR G-amida
107
HGEGT FTSDV SSYLE OQAADEFIAW LVKGR GCA-amida
108
HGEGT FTSDV SSYLE OQAADEFIAW LVKGR GCSG-amida
109
HGEGT FTSDV SOYLE DQAAK EFIAW LVKGR G[K/O/C]-amida
110
HGEGT FTSDV SSOLE GDAAK EFIAW LVKGR G[K/O/C]-amida
111
HGEGT FTSDV SSYOE GQDAK EFIAW LVKGR G[K/O/C]-amida
112
HGEGT FTSDV SSYLO GQADK EFIAW LVKGR G[K/O/C]-amida
113
HGEGT FTSDV SSYLE OQAADEFIAW LVKGR G[K/O/C]-amida
114
HGEGT FTSDV SSYLE GOAAKDFIAW LVKGR G[K/O/C]-amida
115
HGEGT FTSDV SSYLE GQOAK EDIAW LVKGR G[K/O/C]-amida
116
HGEGT FTSDV SSYLE GQAOK EFDAW LVKGR G[K/O/C]-amida
117
HGEGT FTSDV SSYLE GQAAOEFIDW LVKGR G[K/O/C]-amida
118
HGEGT FTSDV SSYLE GQAAOEFIAW LVKGR G[K/O/C]-amida
G8 ciclo [21-26] -Lys/Orn/Cys 38 119
HGEGT FTSDV SSYLO GQAAEEFIAW LVKGR G[K/O/C]-amida
120
HGEGT FTSDV SSYLE GQAAKEFIAW LVKGR G[K/O/C]-amida
G8 ciclo [21-26] -Lys/Orn/Cys 38 121
HGEGT FTSDV SSYLK GQAAEEFIAW LVKGR G[K/O/C]-amida
122
HGEGT FTSDV SSYLJ GQAAKEFIAW LVKGR G[K/O/C]-amida
123
HGEGT FTSDV SSYLK GQAAJEFIAW LVKGR G[K/O/C]-amida
124
HGEGT FTSDV SSYLD GQAAOEFIAW LVKGR G[K/O/C]-amida
125
HGEGT FTSDV SSYLO GQAADEFIAW LVKGR G[K/O/C]-amida
126
HGEGT FTSDV SSYLD GQAAKEFIAW LVKGR G[K/O/C]-amida
127
HGEGT FTSDV SSYLK GQAADEFIAW LVKGR G[K/O/C]-amida
128
HGEGT FTSDV SSYL [Cpa] GQAAO EFIAW LVKGR G[K/O/C]-amida
129
HGEGT FTSDV SSYLO GQAA [Cpa] EFIAW LVKGR G[K/O/C]-amida
130
HGEGT FTSDV SSYL [Cpa]GQAAK EFIAW LVKGR G[K/O/C]-amida
131
HGEGT FTSDV SSYLK GQAA[Cpa] EFIAW LVKGR G[K/O/C]-amida
132
HGEGT FTSDV SSYLB GQAAKEFIAW LVKGR G[K/O/C]-amida
133
HGEGT FTSDV SSYLK GQAABEFIAW LVKGR G[K/O/C]-amida
134
HGEGT FTSDV SSYLE DQAAKEFIAW LVKGR G-amida
cicloD22-K26 135
HGEGT FTSDV SSYLE DQAAKEFIAW LVKGR GCA-amida
cicloD22-K26 136
HGEGT FTSDV SSYLE DQAAKEFIAW LVKGR GCSG-amida
cicloD22-K26/CSG 137
HGEGT FTSDV SDYLE KQAAK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [18-22] -Lys/Orn/Cys 38 138
HGEGT FTSDV SSDLE GKAAK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [19-23] -Lys/Orn/Cys 38 139
HGEGT FTSDV SSYDE GQKAK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [20-24] -Lys/Orn/Cys 38 140
HGEGT FTSDV SSYLD GQAKK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [21-25] -Lys/Orn/Cys 38 141
HGEGT FTSDV SSYLE DQAAKEFIAW LVKGR G[K/O/C]-amida
G8 ciclo [22-26] 142
24
E07761068
25-08-2014
Análogo de GLP-1
Ref. interna SEC ID Nº:
-Lys/Orn/Cys 38
HGEGT FTSDV SSYLE GDAAKKFIAW LVKGR G[K/O/C]-amida
G8 ciclo [23-27] -Lys/Orn/Cys 38 143
HGEGT FTSDV SSYLE GQDAK EKIAW LVKGR G[K/O/C]-amida
G8 ciclo [24-28] -Lys/Orn/Cys 38 144
HGEGT FTSDV SSYLE GQADK EFKAW LVKGR G[K/O/C]-amida
G8 ciclo [25-29] -Lys/Orn/Cys 38 145
HGEGT FTSDV SSYLE GQAADEFIKW LVKGR G[K/O/C]-amida
G8 ciclo [26-30] -Lys/Orn/Cys 38 146
HGEGT FTSDV SSYLE KQAADEFIAW LVKGR G-amida
147
HGEGT FTSDV SSYLE KQAADEFIAW LVKGR GCA-amida
148
HGEGT FTSDV SSYLE KQAADEFIAW LVKGR GCSG-amida
149
HGEGT FTSDV SKYLE DQAAK EFIAW LVKGR G[K/O/C]-amida
150
HGEGT FTSDV SSKLE GDAAK EFIAW LVKGR G[K/O/C]-amida
151
HGEGT FTSDV SSYKE GQDAK EFIAW LVKGR G[K/O/C]-amida
152
HGEGT FTSDV SSYLK GQADK EFIAW LVKGR G[K/O/C]-amida
153
HGEGT FTSDV SSYLE KQAADEFIAW LVKGR G[K/O/C]-amida
154
HGEGT FTSDV SSYLE GKAAKDFIAW LVKGR G[K/O/C]-amida
155
HGEGT FTSDV SSYLE GQKAK EDIAW LVKGR G[K/O/C]-amida
156
HGEGT FTSDV SSYLE GQAKK EFDAW LVKGR G[K/O/C]-amida
157
HGEGT FTSDV SSYLE GQAKKEFIDW LVKGR G[K/O/C]-amida
158
HGEGT FTSDV SSYLE KQAAEEFIAW LVKGR G-amida
GLP1 (7-37) ciclo [Lys16-Glu20] 159
HGEGT FTSDV SSYLE KQAAEEFIAW LVKGR GCA-amida
cicloK22-E26 160
HGEGT FTSDV SSYLE KQAAEEFIAW LVKGR GCSG-amida
cicloK22-E26/CSG 161
HGEGT FTSDV SKYLE EQAAK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [18-22] -Lys/Orn/Cys 38 162
HGEGT FTSDV SSKLE GEAAK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [19-23] -Lys/Orn/Cys 38 163
HGEGT FTSDV SSYKE GQEAK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [20-24] -Lys/Orn/Cys 38 164
HGEGT FTSDV SSYLK GQAEK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [21-25] -Lys/Orn/Cys 38 165
HGEGT FTSDV SSYLE KQAAEEFIAW LVKGR G[K/O/C]-amida
G8 ciclo [22-26] -Lys/Orn/Cys 38 166
HGEGT FTSDV SSYLE GKAAKEFIAW LVKGR G[K/O/C]-amida
G8 ciclo [23-27] -Lys/Orn/Cys 38 167
HGEGT FTSDV SSYLE GQKAK EEIAW LVKGR G[K/O/C]-amida
GB ciclo [24-28] -Lys/Orn/Cys 38 168
HGEGT FTSDV SSYLE GQAKK EFEAW LVKGR G[K/O/C]-amida
G8 ciclo [25-29] -Lys/Orn/Cys 38 169
HGEGT FTSDV SSYLE GQAAKEFIEW LVKGR G[K/O/C]-amida
G8 ciclo [26-30] -Lys/Orn/Cys 38 170
HGEGT FTSDV SS[Cpa]LE GQAAK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo[19-26] -Lys/Orn/Cys 38 171
HGEGT FTSDV SSKLE GQAA[Cpa] EFIAW LVKGR G[K/O/C]-amida
172
HGEGT FTSDV SS[Cpa]LE GQAAO EFIAW LVKGR G[K/O/C]-amida
G8 ciclo[19-26] -Lys/Orn/Cys 38 173
HGEGT FTSDV SSOLE GQAA[Cpa] EFIAW LVKGR G[K/O/C]-amida
174
HGEGT FTSDL SSYLE BQAAKEFIAW LVKGR G-amida
175
HGEGT FTSDV SSYLE BQAAKEFIAW LVKGR GCA-amida
176
HGEGT FTSDV SSYLE BQAAKEFIAW LVKGR GCSG-amida
177
HGEGT FTSDV SBYLE KQAAK EFIAW LVKGR G[K/O/C]-amida
G8 ciclo [18-22] -Lys/Orn/Cys 38 178
HGEGT FTSDV SSBLE GKAAK EFIAW LVKGR G[K/O/C]-amida
179
HGEGT FTSDV SSYBE GQKAK EFIAW LVKGR G[K/O/C]-amida
180
HGEGT FTSDV SSYLB GQAKK EFIAW LVKGR G[K/O/C]-amida
181
HGEGT FTSDV SSYLE BQAAKEFIAW LVKGR G[K/O/C]-amida
182
HGEGT FTSDV SSYLE GBAAKKFIAW LVKGR G[K/O/C]-amida
183
HGEGT FTSDV SSYLE GQBAK EKIAW LVKGR G[K/O/C]-amida
184
HGEGT FTSDV SSYLE GQABK EFKAW LVKGR G[K/O/C]-amida
185
25
E07761068
25-08-2014
Análogo de GLP-1
Ref. interna SEC ID Nº:
HGEGT FTSDV SSYLE GQAABEFIKW LVKGR G[K/O/C]-amida
186
HGEGT FTSDV SKYLE BQAAK EFIAW LVKGR G[K/O/C]-amida
187
HGEGT FTSDV SSYLE KQAABEFIAW LVKGR G-amida
188
HGEGT FTSDV SSYLE KQAABEFIAW LVKGR GCA-amida
189
HGEGT FTSDV SSYLE KQAABEFIAW LVKGR GCSG-amida
190
HGEGT FTSDV SSKLE GBAAK EFIAW LVKGR G[K/O/C]-amida
191
HGEGT FTSDV SSYKE GQBAK EFIAW LVKGR G[K/O/C]-amida
192
HGEGT FTSDV SSYLK GQABK EFIAW LVKGR G[K/O/C]-amida
193
HGEGT FTSDV SSYLE KQAABEFIAW LVKGR G[K/O/C]-amida
194
HGEGT FTSDV SSYLE GKAAKBFIAW LVKGR G[K/O/C]-amida
195
HGEGT FTSDV SSYLE GQKAK EBIAW LVKGR G[K/O/C]-amida
196
HGEGT FTSDV SSYLE GQAKK EFBAW LVKGR G[K/O/C]-amida
197
HGEGT FTSDV SSYLE GQAAKEFIBW LVKGR G[K/O/C]-amida
198
HGEGT FTSDV SSYLE[Cpa]QAAK EFIAW LVKGR G-amida
199
HGEGT FTSDV SSYLE[Cpa]QAAK EFIAW LVKGR GCA-amida
200
HGEGT FTSDV SSYLE [Cpa]QAAK EFIAW LVKGR GCSG-amida
201
HGEGT FTSDV S[Cpa]YLEKQAAK EFIAW LVKGR G[K/O/C]-amida
202
HGEGT FTSDV SS[Cpa]LE GKAAK EFIAW LVKGR G[K/O/C]-amida
203
HGEGT FTSDV SSY[Cpa]E GQKAK EFIAW LVKGR G[K/O/C]-amida
204
HGEGT FTSDV SSYL[Cpa]GQAKK EFIAW LVKGR G[K/O/C]-amida
205
HGEGT FTSDV SSYLE[Cpa]QAAK EFIAW LVKGR G[K/O/C]-amida
206
HGEGT FTSDV SSYLE G[Cpa]AAK KFIAW LVKGR G[K/O/C]-amida
207
HGEGT FTSDV SSYLE GQ[Cpa]AK EKIAW LVKGR G[K/O/C]-amida
208
HGEGT FTSDV SSYLE GQA[Cpa]K EFKAW LVKGR G[K/O/C]-amida
209
HGEGT FTSDV SSYLE GQAA[Cpa] EFIKW LVKGR G[K/O/C]-amida
210
HGEGT FTSDV SKYLE[Cpa]QAAK EFIAW LVKGR G[K/O/C]-amida
211
HGEGT FTSDV SSYLEKQAA[Cpa] EFIAW LVKGR G-amida
212
HGEGT FTSDV SSYLEKQAA[Cpa] EFIAW LVKGR GCA-amida
213
HGEGT FTSDV SSYLEKQAA[Cpa] EFIAW LVKGR GCSG-amida
214
HGEGT FTSDV SSKLE G[Cpa]AAK EFIAW LVKGR G[K/O/C]-amida
215
HGEGT FTSDV SSYKE GQ[Cpa]AK EFIAW LVKGR G[K/O/C]-amida
216
HGEGT FTSDV SSYLKGQA[Cpa]K EFIAW LVKGR G[K/O/C]-amida
217
HGEGT FTSDV SSYLEKQAA[Cpa] EFIAW LVKGR G[K/O/C]-amida
218
HGEGT FTSDV SSYLE GKAAK[Cpa]FIAW LVKGR G[K/O/C]-amida
219
HGEGT FTSDV SSYLE GQKAK E[Cpa]IAW LVKGR G[K/O/C]-amida
220
HGEGT FTSDV SSYLE GQAKK EF[Cpa]AW LVKGR G[K/O/C]-amida
221
HGEGT FTSDV SSYLE GQAAKEFI[Cpa]W LVKGR G[K/O/C]-amida
222
HGEGT FTSDV SSYLE[Cpa]QAAO EFIAW LVKGR G-amida
223
HGEGT FTSDV SSYLE[Cpa]QAAO EFIAW LVKGR GCA-amida
224
HGEGT FTSDV SSYLE[Cpa]QAAO EFIAW LVKGR GCSG-amida
225
HGEGT FTSDV S[Cpa]YLEOQAAK EFIAW LVKGR G[K/O/C]-amida
226
HGEGT FTSDV SS[Cpa]LE GOAAK EFIAW LVKGR G[K/O/C]-amida
227
HGEGT FTSDV SSY[Cpa]E GQOAK EFIAW LVKGR G[K/O/C]-amida
228
HGEGT FTSDV SSYL[Cpa]GQAOK EFIAW LVKGR G[K/O/C]-amida
229
HGEGT FTSDV SSYLE[Cpa]QAAO EFIAW LVKGR G[K/O/C]-amida
230
HGEGT FTSDV SSYLE G[Cpa]AAK OFIAW LVKGR G[K/O/C]-amida
231
HGEGT FTSDV SSYLE GQ[Cpa]AK EOIAW LVKGR G[K/O/C]-amida
232
HGEGT FTSDV SSYLE GQA[Cpa]K EFOAW LVKGR G[K/O/C]-amida
233
HGEGT FTSDV SSYLE GQAA[Cpa] EFIOW LVKGR G[K/O/C]-amida
234
HGEGT FTSDV SOYLE[Cpa]QAAK EFIAW LVKGR G[K/O/C]-amida
235
HGEGT FTSDV SSYLEOQAA[Cpa] EFIAW LVKGR G-amida
236
HGEGT FTSDV SSYLEOQAA[Cpa] EFIAW LVKGR GCA-amida
237
HGEGT FTSDV SSYLEOQAA[Cpa] EFIAW LVKGR GCSG-amida
238
HGEGT FTSDV SSOLE G[Cpa]AAK EFIAW LVKGR G[K/O/C]-amida
239
HGEGT FTSDV SSYOE GQ[Cpa]AK EFIAW LVKGR G[K/O/C]-amida
240
HGEGT FTSDV SSYLOGQA[Cpa]K EFIAW LVKGR G[K/O/C]-amida
241
HGEGT FTSDV SSYLEOQAA[Cpa] EFIAW LVKGR G[K/O/C]-amida
242
HGEGT FTSDV SSYLE GOAAK[Cpa]FIAW LVKGR G[K/O/C]-amida
243
HGEGT FTSDV SSYLE GQOAK E[Cpa]IAW LVKGR G[K/O/C]-amida
244
HGEGT FTSDV SSYLE GQAOK EF[Cpa]AW LVKGR G[K/O/C]-amida
245
HGEGT FTSDV SSYLE GQAAOEFI[Cpa]W LVKGR G[K/O/C]-amida
246
26
E07761068
25-08-2014
Análogo de GLP-1
Ref. interna SEC ID Nº:
A HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
A-GLP-1 247
G HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
G-GLP-1 248
P HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
P-GLP-1 249
S HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
S-GLP-1 250
T HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
T-GLP-1 251
V HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
V-GLP-1 252
MQ HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
MQ-GLP1 253
MR HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
MR-GLP1 254
MK HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
MK-GLP1 255
M HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
M-GLP1 256
MH HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
MH-GLP1 257
MHH HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
MHH-GLP1 258
MY HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
MY-GLP1 259
MI HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
MI-GLP1 260
MD HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
MD-GLP1 261
ML HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
ML-GLP1 262
MN HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
MN-GLP1 263
ME HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
ME-GLP1 264
MW HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
MW-GLP1 265
MF HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
MF-GLP1 266
MM HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR
MM-GLP1 267
HGEGT FTSDV SSYLE GQAAK EFIAW LVKGR GCA-amida
268
HGEGT FTSDV SSYLE GQAAK EFIAW LVKGG G
269
HGEGT FTSDV SSYLE GQAAK EFIAW LKNGG G
270
HGEGT FTSDL SKQME EEAVR LFIEW LKNGG-amida
271
HGEGT FTSDL SKQME ZEAVR LFIEW LKNGG-amida
272
HGEGT FTSDV SSYLE GQAAK EFIAW L
273
HGEGT FTSDV SSYLE EQAKK EFIAW LVKGR G-amida
274
HGEGT FTSDV SSYLE EQAKK EFIAW LVKGR GCGS-amida
275
HGEGT FTSDV SSYLE GQAKK EFIAW LEKGR K-amida
277
HGEGT FTSDV SSYLEEQAADab EFIAW LVKGR G-amida
279
HGEGT FTSDV SSYLEEQAADab EFIAW LVKGR GCA-amida
280
HGEGT FTSDV SSYLEEQAADab EFIAW LVKGR GCSG-amida
281
HGEGT FTSDV SEYLEDabQAAK EFIAW LVKGR G[K/O/C]-amida
282
HGEGT FTSDV SSELE GDabAAK EFIAW LVKGR G[K/O/C]-amida
283
HGEGT FTSDV SSYEE GQDabAK EFIAW LVKGR G[K/O/C]-amida
284
HGEGT FTSDV SSYLEGQADabK EFIAW LVKGR G[K/O/C]-amida
285
HGEGT FTSDV SSYLEEQAADab EFIAW LVKGR G[K/O/C]-amida
286
HGEGT FTSDV SSYLE GEAAKDabFIAW LVKGR G[K/O/C]-amida
287
HGEGT FTSDV SSYLE GQEAK EDabIAW LVKGR G[K/O/C]-amida
288
HGEGT FTSDV SSYLE GQAEK EFDabAW LVKGR G[K/O/C]-amida
289
HGEGT FTSDV SSYLE GQAAEEFIDabW LVKGR G[K/O/C]-amida
290
HGEGT FTSDV SSYLEGQAADab EFIAW LVKGR G[K/O/C]-amida
291
HGEGT FTSDV SSYLEDabQAAE EFIAW LVKGR G-amida
292
HGEGT FTSDV SSYLEDabQAAE EFIAW LVKGR GCA-amida
293
HGEGT FTSDV SSYLEDabQAAE EFIAW LVKGR GCSG-amida
294
HGEGT FTSDV SDabYLEEQAAK EFIAW LVKGR G[K/O/C]-amida
295
HGEGT FTSDV SSDabLE GEAAK EFIAW LVKGR G[K/O/C]-amida
296
HGEGT FTSDV SSYDabE GQEAK EFIAW LVKGR G[K/O/C]-amida
297
HGEGT FTSDV SSYLDabGQAEK EFIAW LVKGR G[K/O/C]-amida
298
HGEGT FTSDV SSYLEDabQAAE EFIAW LVKGR G[K/O/C]-amida
299
HGEGT FTSDV SSYLE GDabAAK EFIAW LVKGR G[K/O/C]-amida
300
HGEGT FTSDV SSYLE GQDabAK EEIAW LVKGR G[K/O/C]-amida
301
HGEGT FTSDV SSYLE GQADabK EFEAW LVKGR G[K/O/C]-amida
302
HGEGT FTSDV SSYLE GQAADab EFIEW LVKGR G[K/O/C]-amida
303
HGEGT FTSDV SSYLDabGQAAE EFIAW LVKGR G[K/O/C]-amida
304
El término “análogo de GLP-1” también incluye variantes, fragmentos y derivados de los análogos de GLP-1 anteriores que son equivalentes funcionales a uno de los análogos de GLP-1 anteriores en los que la variante, fragmento o derivado tiene una secuencia de aminoácidos similar (por ejemplo, que comprende sustituciones 5 conservativas) y retiene, a cierto grado, al menos una actividad del análogo de GLP-1.
27
imagen21
imagen22
imagen23
imagen24
imagen25
imagen26
imagen27
imagen28
imagen29
imagen30
imagen31
imagen32
E07761068
25-08-2014
cgGLP-6
SEC ID Nº: 10 + mancuerna de PEG de 8k 11 nM -0,1 nM 0,8 nM
cgGLP-8
SEC ID Nº: 10 + PEG de 30k 170 nM 0,4 nM 3 nM
cgGLP-10
SEC ID Nº: 10 + dímero de PEG de 20k 100 nM 0,6 nM 4 nM
cgGLP-16
SEC ID Nº: 10 + PEG de 30k 1 uM 0,39 nM 4 nM
H[Aib]EGT FTSDV SSYLE GQAAK EFIAW LVKGR GCSGG (SEC ID Nº: 11)
100 nM 4 nM >50 nM
cgGLP-17
SEC ID Nº: 11 + PEG de 20k 1 uM 20 nM >100 nM
H[bAla]EGT FTSDV SSYLE GQAAK EFIAW LVKGR GCSGG (SEC ID Nº: 12)
400 nM >100 nM indeterminada
cgGLP-18
SEC ID Nº: 12 + PEG de 20k >1 uM indeterminada indeterminada
Aib = ácido alfaaminobutírico bAla = ácido betaaminopropiónico
Ejemplo 6
Resultados con compuestos relacionados con la fórmula III
5 Se realizaron experimentos in vitro para determinar la potencia y unión del receptor para compuestos de GLP-1 que tienen tanto una sustitución de Aib (ácido 2-aminoisobutírico) como Aad (ácido 2-aminoadípico) en la posición 22 y sustitución opcional en la posición 8 y en el extremo C. Las moléculas pegiladas se conjugaron en la cisteína en la posición 38. Se realizaron experimentos como se describe en el Ejemplo 2, y los resultados se resumen en la Tabla
10 5 a continuación.
Tabla 5
REF INTERNA Nº
SECUENCIA CI50 humana CE50 humana CE50 deratón
HGEGT FTSDV SSYLE [Aib]QAAK EFIAW LVKGR -AMIDA (SEC ID Nº: 14)
2,5 nM 16 pM 0,15 nM
HGEGT FTSDV SSYLE [Aib]QAAK EFIAW LVKGR G-AMIDA (SEC ID Nº: 15)
3,5 nM 27 pM 0,12 nM
cgGLP-23
HGEGT FTSDV SSYLE [Aib]QAAK EFIAW LVKGR GC-AMIDA SEC ID Nº: 17 + PEG de 20k 300 nM 0,2 nM 3 nM
HGEGT FTSDV SSYLE [Aib]QAAK EFIAW LVKGR GCA-AMIDA (SEC ID Nº: 18)
25 pM 0,2 nM
mgGLP32 y mgGLP-20
SEC ID Nº: 18 + PEG de 20k 56 nM 0,13 nM 0,84 nM
HGEGT FTSDV SSYLE [Aib]QAAK EFIAW LVKGR GCG-AMIDA (SEC ID Nº: 20)
mgGLP-16
SEC ID Nº: 20 + PEG de 20k 50 nM 0,2 nM 1,6 nM
HGEGT FTSDV SSYLE [Aib]QAAK EFIAW LVKGR GCSG (SEC ID Nº: 21)
18 nM 68 pM 300 pM
mgGLP19 y cgGLP-19
SEC ID Nº: 21 + PEG de 20k 230 nM 0,32 nM 4 nM
HGEGT FTSDV SSYLE [Aib]QAAK EFIAW LVKGR GCSG-AMIDA (SEC ID Nº: 22)
17 nM 45 pM 0,27 nM
cgGLP-24 cgGLP-27, mgGLP-22, mgGLP-33 y mgGLP-27
SEC ID Nº: 22 + PEG de 20k 47 nM 0,1 nM 0,84 nM
cgGLP-25
SEC ID Nº: 22 + 5k PEG 15 nM 39 pM 0,9 nM
cgGLP-26
SEC ID Nº: 22 + 10k PEG 23 nM 59 pM 0,9 nM
cgGLP-28
SEC ID Nº: 22 + PEG de 30k 71 nM 0,1 nM 0,8 nM
cgGLP-29
SEC ID Nº: 22 + PEG ramificado de 40k 800 nM 0,15 nM 1 nM
HGEGT FTSDV SSYLE [Aib]QAAK EFIAW LVKGR GCSGG-AMIDA (SEC ID
40
E07761068
25-08-2014
REF INTERNA Nº
SECUENCIA CI50 humana CE50 humana CE50 deratón
Nº: 24)
mgGLP-15
SEC ID Nº: 24 + PEG de 20k 100 nM 0,2nM 1,8 nM
H[Aib]EGT FTSDV SSYLE [Aib]QAAK EFIAW LVKGR GCSG (SEC ID Nº: 25)
cgGLP-20
SEC ID Nº: 25 + mPEG de 20k 30 nM 99 pM 1,5 nM
Ejemplo 7
Resultados con compuestos de GLP-1 cíclico
5 Se realizaron experimentos in vitro para determinar la potencia y unión del receptor para una variedad de compuestos de GLP-1 en los que las cadenas laterales de ciertos aminoácidos se unieron para formar un anillo (una lactama cíclica). Se realizaron experimentos como se describe en el Ejemplo 2. Las secuencias de los compuestos cíclicos probados se muestran en la Tabla 6 junto con los resultados. Las cadenas laterales de los aminoácidos que
10 participaron en la formación de la lactama cíclica se muestran en negrita y subrayadas. De los compuestos enumerados en la Tabla 6, solo mgGLP-24 se pegiló.
Tabla 6
REF INTERNA Nº
SECUENCIA CI50 humana CE50 humana CE50 deratón
[Gly8]GLP1(7-37) ciclo[Glu14-Lys18]
HGEGT FTSDV SSYEE GQKAK EFIAW LVKGR G AMIDA (SEC ID Nº: 35) 12 pM 0,21 nM
[Gly8]GLP1(7-37) ciclo[Glu15-Lys19]
HGEGT FTSDV SSYLE GQAKK EFIAW LVKGR G AMIDA (SEC ID Nº: 36) 0,15 nM 66 pM
GLP1(7-37) ciclo[Glu15-Lys19; 27-31]
HGEGT FTSDV SSYLE GQAKK EFIAW LEKGR K AMIDA (SEC ID Nº: 277) indeterminada indeterminada
[Gly8]ciclo[2126]GLP1(7-37)amida
HGEGT FTSDV SSYLE GQAAKEFIAW LVKGR G AMIDA (SEC ID Nº: 42) 0,6 nM indeterminada
cicloE22-K26
HGEGT FTSDV SSYLE EQAAKEFIAW LVKGR G -AMIDA (SEC ID Nº: 30) 1,1 nM 9 pM 68 pM
mgGLP24
SEC ID Nº: 30 + mPEG de 20k 48 nM 0,25 nM 0,9 nM
cicloE22-026
HGEGT FTSDV SSYLE EQAAOEFIAW LVKGR G -AMIDA (SEC ID Nº: 69) 3,7 nM 51 pM 0,25 nM
GLP1(7-37) ciclo[Lys16-Glu20]
HGEGT FTSDV SSYLE KQAAEEFIAW LVKGR G AMIDA (SEC ID Nº: 159) 16 pM 0,1 nM
Gly8]GLP1(7-37) ciclo[Glu17-Lys21]
HGEGT FTSDV SSYLE GEAAKKFIAW LVKGR G AMIDA (SEC ID Nº: 38) 18 pM 0,17 nM
[Gly8]GLP1(7-37) ciclo[Glu18-Lys22]
HGEGT FTSDV SSYLE GQEAK EKIAW LVKGR G AMIDA (SEC ID Nº: 39) 0,8 nM indeterminada
O= ornitina = aa sin cadena lateral de CH2CH2CH2NH3
15 Ejemplo 8 Resultados con compuestos de GLP-1 que tienen extensión del extremo N
Se realizaron experimentos in vitro para determinar la potencia y unión del receptor para compuestos de GLP-1 que 20 tienen una extensión del extremo N. Se realizaron experimentos como se describe en el Ejemplo 2, y los resultados se resumen en la Tabla 7 a continuación. No se pegiló ninguno de los compuestos enumerados en la Tabla 7.
Tabla 7
REF INTERNA Nº
SECUENCIA CI50 humana CE50 humana CE50 deratón
A-GLP-1
A HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR (SEC ID Nº: 247) 38 nM 0,2 nM 0,8 nM
G-GLP-1
G HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR (SEC ID Nº: 248) 80 nM 1 nM 3 nM
P-GLP-1
P HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR (SEC ID Nº: 249) 38 nM 0,2 nM 1 nM
S-GLP-1
S HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR (SEC ID Nº: 250) 53 nM 0,4 nM 2 nM
T-GLP-1
T HAEGT FTSDV SSYLE GQAAK 53 nM 0,3 nM 2 nM
41
E07761068
25-08-2014
EFIAW LVKGR (SEC ID Nº: 251)
V-GLP-1
V HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR (SEC ID Nº: 252) 32 nM 0,2 nM 1 nM
MQ-GLP1
MQ HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR (SEC ID Nº: 253) 64 nM 0,5 nM 3,0 nM
MR-GLP1
MR HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR (SEC ID Nº: 254) 590 nM 8 nM 41 nM
MK-GLP1
MK HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR (SEC ID Nº: 255) 760 nM 4 nM 12 nM
M-GLP1
M HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR (SEC ID Nº: 256) 18 nM 86 pM 0,5 nM
KH-GLP1
MH HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR (SEC ID Nº: 257) 350 nM 2 nM 11 nM
MHH-GLP1
MHH HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR (SEC ID Nº: 258) 350 nM 1,0 nM 5 nM
MY-GLP1
MY HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR (SEC ID Nº: 259) 57 nM 0,4 nM 1 nM
MI-GLP1
MI HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR (SEC ID Nº: 260) 75 nM 0,6 nM 6 nM
' MD-GLP1
MD HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR (SEC ID Nº: 261) 82 nM 0,3 nM 2 nM
ML-GLP1
ML HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR (SEC ID Nº: 262) 160 nM 0,7 nM 6 nM
MN-GLP1
MN HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR (SEC ID Nº: 263) 50 nM 0,3 nM 2 nM
ME-GLP1
ME HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR (SEC ID Nº: 264) 95 nM 1 nM 4 nM
MW-GLP1
MW HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR (SEC ID Nº: 265) 79 nM 0,8 nM 5 nM
MF-GLP1
MF HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR (SEC ID Nº: 266) 180 nM 1 nM 6 nM
MM-GLP1
MM HAEGT FTSDV SSYLE GQAAK EFIAW LVKGR (SEC ID Nº: 267) 100 nM 0,5 nM 3 nM
Ejemplo 9
Resultados in vivo -Efecto sobre los niveles de glucosa en sangre con el tiempo
5 Se probaron una variedad de diferentes compuestos de GLP-1, que incluyen representantes de las diferentes clases desveladas en el presente documento (por ejemplo, compuestos que tienen la estructura general de fórmulas I-IV descritas anteriormente), para su capacidad para afectar niveles de glucosa en sangre. En estos experimentos la glucosa en sangre se midió en ratones db/db como se describe en el Ejemplo 3.
10 La Figura 12 muestra la capacidad de cgGLP-17, cgGLP-18, cgGLP-19, mgGLP-09A (véanse las Tablas 4 y 5 para secuencias y tamaño y tipo de PEG) y mg-GLP-09A para reducir la glucosa en sangre durante un periodo de tiempo de 72 horas. Cada uno de estos compuestos redujo la glucosa en sangre con respecto al control, reduciendo cgGLP-19 la glucosa en sangre durante el periodo de tiempo más largo (se necesitaron 72 horas a una dosis de 10
15 ug/ratón para que los niveles de glucosa en el ratón volvieran a los niveles normales). Se realizó otro conjunto de experimentos con cgGLP-19, cgGLP-20, cgGLP-23, cgGLP-24 (véase la Tabla 5 para secuencias y tamaño y tipo de PEG). Se inyectaron 10 ug de compuesto de GLP-1 en cada ratón. Como se muestra en la Figura 13, estos cuatro compuestos de GLP-1 mostraron capacidad similar para reducir los niveles de glucosa en sangre con el tiempo, causando cada uno una disminución significativa en los niveles de glucosa en sangre durante un periodo de tiempo
20 de 48 horas.
Se realizaron otro conjunto de experimentos usando mgGLP-20, cgGLP-26, mgGLP-22 y mgGLP-24 (véanse las Tablas 5 y 6 para secuencias y tamaño y tipo de PEG). La dosificación fue 10 ug por ratón. Como se muestra en la Figura 14, aunque cada compuesto redujo los niveles de glucosa en sangre, lo hicieron de manera diferente. En este
25 ejemplo, mgGLP-20 y mgGLP-24 redujeron la glucosa durante el mayor periodo de tiempo. Con estos dos compuestos se necesitaron 72 horas para que los niveles de glucosa en sangre volvieran a los niveles normales.
Ejemplo 10
30 Reducción de la glucosa en sangre en un modo dependiente de la dosis
42
imagen33

Claims (1)

  1. imagen1
    imagen2
ES07761068.1T 2006-04-20 2007-04-20 Compuestos de GLP-1 Active ES2495741T3 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US79370706P 2006-04-20 2006-04-20
US793707P 2006-04-20
PCT/US2007/067150 WO2007124461A2 (en) 2006-04-20 2007-04-20 Glp-1 compounds

Publications (1)

Publication Number Publication Date
ES2495741T3 true ES2495741T3 (es) 2014-09-17

Family

ID=38625788

Family Applications (1)

Application Number Title Priority Date Filing Date
ES07761068.1T Active ES2495741T3 (es) 2006-04-20 2007-04-20 Compuestos de GLP-1

Country Status (8)

Country Link
US (2) US8288339B2 (es)
EP (3) EP2574624A1 (es)
JP (2) JP2009534423A (es)
AU (1) AU2007240313B2 (es)
CA (2) CA2648936C (es)
ES (1) ES2495741T3 (es)
MX (1) MX2008013304A (es)
WO (1) WO2007124461A2 (es)

Families Citing this family (68)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2570133B1 (en) 2005-11-07 2016-03-23 Indiana University Research and Technology Corporation Glucagon analogs exhibiting physiological solubility and stability
AU2008216265B2 (en) 2007-02-15 2014-04-03 Indiana University Research And Technology Corporation Glucagon/GLP-1 receptor co-agonists
GB2448895A (en) * 2007-05-01 2008-11-05 Activotec Spp Ltd GLP-1 like compounds and uses thereof
EP2025674A1 (de) 2007-08-15 2009-02-18 sanofi-aventis Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
US8980830B2 (en) 2007-10-30 2015-03-17 Indiana University Research And Technology Corporation Peptide compounds exhibiting glucagon antagonist and GLP-1 agonist activity
EP2300037B1 (en) 2008-06-17 2016-03-30 Indiana University Research and Technology Corporation Glucagon/glp-1 receptor co-agonists
DK2300035T3 (en) 2008-06-17 2015-11-16 Univ Indiana Res & Tech Corp Mixed GIP-based agonists for the treatment of metabolic diseases and obesity
CN102325539A (zh) 2008-12-19 2012-01-18 印第安纳大学研究及科技有限公司 基于酰胺的胰高血糖素超家族肽前药
AU2009334289A1 (en) * 2008-12-29 2011-07-28 Panacea Biotec Ltd GLP-1 analogs and uses thereof
WO2010118034A2 (en) * 2009-04-06 2010-10-14 Board Of Regents, The University Of Texas System Cyclic peptide analogues for non-invasive imaging of pancreatic beta-cells
WO2010148089A1 (en) 2009-06-16 2010-12-23 Indiana University Research And Technology Corporation Gip receptor-active glucagon compounds
US8614182B2 (en) 2009-07-30 2013-12-24 Jiangsu Hansoh Pharmaceuticals Co., Ltd. GLP-1 analogues and their pharmaceutical salts and uses
CN101987868B (zh) * 2009-07-30 2013-09-04 江苏豪森医药集团有限公司 Glp-1类似物的衍生物或其可药用盐和用途
NZ599847A (en) * 2009-11-13 2013-09-27 Sanofi Aventis Deutschland Pharmaceutical composition comprising a glp-1 agonist and methionine
EP2528618A4 (en) 2010-01-27 2015-05-27 Univ Indiana Res & Tech Corp GLUCAGON ANTAGONISTE AND GIP AGONISTS CONJUGATES AND COMPOSITIONS FOR THE TREATMENT OF METABOLISM DISEASES AND ADIPOSITAS
WO2011107494A1 (de) 2010-03-03 2011-09-09 Sanofi Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung
DE102010015123A1 (de) 2010-04-16 2011-10-20 Sanofi-Aventis Deutschland Gmbh Benzylamidische Diphenylazetidinone, diese Verbindungen enthaltende Arzneimittel und deren Verwendung
CA2797095A1 (en) 2010-05-13 2011-11-17 Indiana University Research And Technology Corporation Glucagon superfamily peptides exhibiting nuclear hormone receptor activity
WO2011143788A1 (en) * 2010-05-17 2011-11-24 Zhejiang Beta Pharma Inc. Novel glucagon like peptide analogs, composition, and method of use
WO2011157827A1 (de) 2010-06-18 2011-12-22 Sanofi Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen
US8530413B2 (en) 2010-06-21 2013-09-10 Sanofi Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments
RU2580317C2 (ru) 2010-06-24 2016-04-10 Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн Пептидные пролекарства, принадлежащие к суперсемейству амид-содержащих глюкагонов
TW201215387A (en) 2010-07-05 2012-04-16 Sanofi Aventis Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament
TW201221505A (en) 2010-07-05 2012-06-01 Sanofi Sa Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament
TW201215388A (en) 2010-07-05 2012-04-16 Sanofi Sa (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments
US8507428B2 (en) 2010-12-22 2013-08-13 Indiana University Research And Technology Corporation Glucagon analogs exhibiting GIP receptor activity
US8871758B2 (en) 2011-03-08 2014-10-28 Sanofi Tetrasubstituted oxathiazine derivatives, method for producing them, their use as medicine and drug containing said derivatives and the use thereof
WO2012120052A1 (de) 2011-03-08 2012-09-13 Sanofi Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung
EP2683699B1 (de) 2011-03-08 2015-06-24 Sanofi Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung
EP2683705B1 (de) 2011-03-08 2015-04-22 Sanofi Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung
US8828995B2 (en) 2011-03-08 2014-09-09 Sanofi Branched oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
BR112013032717A2 (pt) 2011-06-22 2017-01-24 Univ Indiana Res & Tech Corp coagonistas do receptor de glucagon/glp-1
RS56173B1 (sr) 2011-06-22 2017-11-30 Univ Indiana Res & Tech Corp Koagonisti receptora za glukagon/glp-1 receptora
WO2013004983A1 (en) 2011-07-04 2013-01-10 Imperial Innovations Limited Novel compounds and their effects on feeding behaviour
CN107090028A (zh) 2011-08-30 2017-08-25 梅约医学教育与研究基金会 利钠多肽
WO2013037390A1 (en) 2011-09-12 2013-03-21 Sanofi 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors
EP2567959B1 (en) 2011-09-12 2014-04-16 Sanofi 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors
EP2760862B1 (en) 2011-09-27 2015-10-21 Sanofi 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors
EP2578599A1 (en) 2011-10-07 2013-04-10 LanthioPep B.V. Cyclic analogs of GLP-1 and GLP-1 related peptides
RU2014117678A (ru) 2011-11-17 2015-12-27 Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн Пептиды глюкагонового суперсемейства, обладающие глюкокортикоидной рецепторной активностью
US9611305B2 (en) 2012-01-06 2017-04-04 Mayo Foundation For Medical Education And Research Treating cardiovascular or renal diseases
CA2877358A1 (en) 2012-06-21 2013-12-27 Indiana University Research And Technology Corporation Glucagon analogs exhibiting gip receptor activity
WO2014064215A1 (en) 2012-10-24 2014-05-01 INSERM (Institut National de la Santé et de la Recherche Médicale) TPL2 KINASE INHIBITORS FOR PREVENTING OR TREATING DIABETES AND FOR PROMOTING β-CELL SURVIVAL
WO2014127120A1 (en) 2013-02-15 2014-08-21 Mayo Foundation For Medical Education And Research Insulin secreting polypeptides
CN112043835B (zh) 2013-12-06 2022-10-21 韩捷 用于含氮和羟基的药物的生物可逆引入基团
MY185334A (en) 2014-12-30 2021-05-06 Hanmi Pharm Ind Co Ltd Glucagon derivatives with improved stability
US10426818B2 (en) 2015-03-24 2019-10-01 Inserm (Institut National De La Sante Et De La Recherche Medicale) Method and pharmaceutical composition for use in the treatment of diabetes
EA201890058A1 (ru) 2015-06-30 2018-07-31 Ханми Фарм. Ко., Лтд. Производное глюкагона и композиция, содержащая длительно действующий конъюгат этого производного
WO2017116204A1 (ko) * 2015-12-31 2017-07-06 한미약품 주식회사 글루카곤, glp-1 및 gip 수용체 모두에 활성을 갖는 삼중 활성체
CN107236033B (zh) * 2016-03-29 2019-12-17 天津药物研究院有限公司 一种胰高血糖素样肽-1类似物及其制备方法和用途
JP7091255B2 (ja) 2016-05-06 2022-06-27 アイオニス・ファーマシューティカルズ・インコーポレイテッド Ｇｌｐ－１受容体リガンド部分コンジュゲート化オリゴヌクレオチドおよびその使用
KR102005457B1 (ko) 2016-06-29 2019-07-30 한미약품 주식회사 글루카곤 유도체, 이의 결합체, 및 이를 포함하는 조성물, 및 이의 치료적 용도
BR112019014588A2 (pt) 2017-01-17 2020-02-18 Amgen Inc. Método de tratamento ou amenização de distúrbios metabólicos usando agonistas do receptor de glp-1 conjugados a antagonistas para receptor do peptídeo inibidor gástrico (gipr)
CN110545838A (zh) * 2017-03-08 2019-12-06 因塔西亚制药公司 用于从药物递送装置施用致恶心化合物的设备和方法
CN109384839B (zh) * 2017-08-04 2021-03-09 天津药物研究院有限公司 胰高血糖素样肽-1类似物及其用途
KR20210109552A (ko) 2018-12-21 2021-09-06 지앙수 헨그루이 메디슨 컴퍼니 리미티드 이중특이적 단백질
WO2020214012A1 (ko) * 2019-04-19 2020-10-22 한미약품 주식회사 글루카곤, glp-1 및 gip 수용체 모두에 활성을 갖는 삼중 활성체 또는 이의 결합체를 포함하는 고지혈증 예방 또는 치료용 약학적 조성물 및 예방 또는 치료 방법
WO2020214013A1 (ko) * 2019-04-19 2020-10-22 한미약품 주식회사 글루카곤, glp-1 및 gip 수용체 모두에 활성을 갖는 삼중 활성체 또는 이의 결합체의 고지혈증에 대한 치료적 용도
AU2020397917A1 (en) 2019-12-04 2022-06-23 The Scripps Research Institute GLP2 receptor agonists and methods of use
PE20221595A1 (es) * 2020-01-13 2022-10-10 Hanmi Pharm Ind Co Ltd Uso terapeutico de un conjugado de accion prolongada de un triple agonista que tiene actividad en todos los receptores de glucagon/glp-1/gip para enfermedades pulmonares
BR112022020531A2 (pt) * 2020-04-20 2022-12-06 Hanmi Pharm Ind Co Ltd Composição farmacêutica
BR112022023609A2 (pt) * 2020-05-22 2023-02-07 Hanmi Pharm Ind Co Ltd Formulação líquida de conjugado de ação prolongada de agonista trigonal de glucagon, glp-1 e gip
US20230381281A1 (en) * 2020-10-16 2023-11-30 Hanmi Pharm. Co., Ltd. Pharmaceutical composition comprising glucagon/glp-1/gip triple agonist or long-acting conjugate thereof for preventing or treating lupus-related diseases
EP4321170A4 (en) * 2021-04-09 2025-07-16 Hanmi Pharmaceutical Co Ltd PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING CHRONIC KIDNEY DISEASE CONTAINING A GLUCAGON DERIVATIVE
MX2023014771A (es) 2021-06-09 2024-03-19 Scripps Research Inst Conjugados peptidicos duales gip/glp-1 de accion prolongada y metodos de uso.
KR20230095665A (ko) * 2021-12-22 2023-06-29 한미약품 주식회사 간 표적 약물 및 이의 용도
CN117186206B (zh) * 2023-10-20 2024-07-23 广东药科大学 新型不同glp1类似肽共价聚合体及其制备方法和应用
WO2025235379A1 (en) * 2024-05-06 2025-11-13 Mayo Foundation For Medical Education And Research Polypeptides having natriuretic and insulin-secreting actions, and methods for their use

Family Cites Families (72)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4002531A (en) 1976-01-22 1977-01-11 Pierce Chemical Company Modifying enzymes with polyethylene glycol and product produced thereby
IE50892B1 (en) 1980-02-11 1986-08-06 Novo Industri As Process for preparing insulin esters
US4399216A (en) 1980-02-25 1983-08-16 The Trustees Of Columbia University Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials
MX7065E (es) 1980-06-06 1987-04-10 Sankyo Co Un procedimiento microbiologico para preparar derivados de ml-236b
US5354772A (en) 1982-11-22 1994-10-11 Sandoz Pharm. Corp. Indole analogs of mevalonolactone and derivatives thereof
US4740461A (en) 1983-12-27 1988-04-26 Genetics Institute, Inc. Vectors and methods for transformation of eucaryotic cells
US5118666A (en) * 1986-05-05 1992-06-02 The General Hospital Corporation Insulinotropic hormone
US5614492A (en) * 1986-05-05 1997-03-25 The General Hospital Corporation Insulinotropic hormone GLP-1 (7-36) and uses thereof
US5120712A (en) 1986-05-05 1992-06-09 The General Hospital Corporation Insulinotropic hormone
US6849708B1 (en) * 1986-05-05 2005-02-01 The General Hospital Corporation Insulinotropic hormone and uses thereof
ATE110083T1 (de) 1986-05-05 1994-09-15 Gen Hospital Corp Insulinotropes hormon.
US4959455A (en) 1986-07-14 1990-09-25 Genetics Institute, Inc. Primate hematopoietic growth factors IL-3 and pharmaceutical compositions
US4912040A (en) 1986-11-14 1990-03-27 Genetics Institute, Inc. Eucaryotic expression system
US4871721A (en) 1988-01-11 1989-10-03 E. R. Squibb & Sons, Inc. Phosphorus-containing squalene synthetase inhibitors
US4924024A (en) 1988-01-11 1990-05-08 E. R. Squibb & Sons, Inc. Phosphorus-containing squalene synthetase inhibitors, new intermediates and method
US5349052A (en) 1988-10-20 1994-09-20 Royal Free Hospital School Of Medicine Process for fractionating polyethylene glycol (PEG)-protein adducts and an adduct for PEG and granulocyte-macrophage colony stimulating factor
EP0401384B1 (en) 1988-12-22 1996-03-13 Kirin-Amgen, Inc. Chemically modified granulocyte colony stimulating factor
US5753675A (en) 1989-03-03 1998-05-19 Novartis Pharmaceuticals Corporation Quinoline analogs of mevalonolactone and derivatives thereof
JPH04504246A (ja) 1989-03-20 1992-07-30 ザ・ジェネラル・ホスピタル・コーポレーション インシュリン刺激ホルモン
US5122614A (en) 1989-04-19 1992-06-16 Enzon, Inc. Active carbonates of polyalkylene oxides for modification of polypeptides
US5324844A (en) 1989-04-19 1994-06-28 Enzon, Inc. Active carbonates of polyalkylene oxides for modification of polypeptides
ATE164852T1 (de) 1990-01-24 1998-04-15 Douglas I Buckley Glp-1-analoga verwendbar in der diabetesbehandlung
US5545618A (en) * 1990-01-24 1996-08-13 Buckley; Douglas I. GLP-1 analogs useful for diabetes treatment
US5177080A (en) 1990-12-14 1993-01-05 Bayer Aktiengesellschaft Substituted pyridyl-dihydroxy-heptenoic acid and its salts
US5445090A (en) 1991-07-25 1995-08-29 Mim Industries, Inc. Interchangeable clamp for use in a sewing machine
US6197925B1 (en) * 1991-08-22 2001-03-06 Sara Lee Corporation NF-AT polypeptides and polynucleotides
US5595872A (en) 1992-03-06 1997-01-21 Bristol-Myers Squibb Company Nucleic acids encoding microsomal trigyceride transfer protein
US5470845A (en) 1992-10-28 1995-11-28 Bristol-Myers Squibb Company Methods of using α-phosphonosulfonate squalene synthetase inhibitors including the treatment of atherosclerosis and hypercholesterolemia
US6284727B1 (en) * 1993-04-07 2001-09-04 Scios, Inc. Prolonged delivery of peptides
NZ250844A (en) 1993-04-07 1996-03-26 Pfizer Treatment of non-insulin dependant diabetes with peptides; composition
GB9317618D0 (en) 1993-08-24 1993-10-06 Royal Free Hosp School Med Polymer modifications
US5446090A (en) 1993-11-12 1995-08-29 Shearwater Polymers, Inc. Isolatable, water soluble, and hydrolytically stable active sulfones of poly(ethylene glycol) and related polymers for modification of surfaces and molecules
US5705483A (en) * 1993-12-09 1998-01-06 Eli Lilly And Company Glucagon-like insulinotropic peptides, compositions and methods
US5385929A (en) 1994-05-04 1995-01-31 Warner-Lambert Company [(Hydroxyphenylamino) carbonyl] pyrroles
US5932462A (en) 1995-01-10 1999-08-03 Shearwater Polymers, Inc. Multiarmed, monofunctional, polymer for coupling to molecules and surfaces
US5962440A (en) 1996-05-09 1999-10-05 Bristol-Myers Squibb Company Cyclic phosphonate ester inhibitors of microsomal triglyceride transfer protein and method
US5885983A (en) 1996-05-10 1999-03-23 Bristol-Myers Squibb Company Inhibitors of microsomal triglyceride transfer protein and method
US6214966B1 (en) 1996-09-26 2001-04-10 Shearwater Corporation Soluble, degradable poly(ethylene glycol) derivatives for controllable release of bound molecules into solution
US5760246A (en) 1996-12-17 1998-06-02 Biller; Scott A. Conformationally restricted aromatic inhibitors of microsomal triglyceride transfer protein and method
DE69800640T2 (de) 1997-01-29 2001-07-05 Polymasc Pharmaceuticals Plc, London Pegylationsverfahren
WO1998043658A1 (en) 1997-03-31 1998-10-08 Eli Lilly And Company Glucagon-like peptide-1 analogs
US6448369B1 (en) 1997-11-06 2002-09-10 Shearwater Corporation Heterobifunctional poly(ethylene glycol) derivatives and methods for their preparation
DK1411075T3 (da) 1998-03-12 2008-10-27 Nektar Therapeutics Al Corp Fremgangsmåde til fremstilling af polymerkonjugater
SK19042000A3 (sk) 1998-06-12 2001-11-06 Bionebraska, Inc. Glukagónu podobný peptid-1 zlepšujúci odpoveď beta-bunkiek na glukózu u subjektov so zhoršenou toleranciou glukózy
DE69922043T2 (de) 1998-12-07 2005-11-24 Société de Conseils de Recherches et d'Applications Scientifiques S.A.S. Glp-1 analoge
JP2002538081A (ja) 1998-12-07 2002-11-12 ソシエテ・ドゥ・コンセイユ・ドゥ・ルシェルシュ・エ・ダプリカーション・シャンティフィック・エス・ア・エス Ｇｌｐ−１の類似体
US6569832B1 (en) * 1999-11-12 2003-05-27 Novo Nordisk A/S Inhibition of beta cell degeneration
AU781839B2 (en) 1999-12-22 2005-06-16 Nektar Therapeutics Sterically hindered derivatives of water soluble polymers
US6413507B1 (en) 1999-12-23 2002-07-02 Shearwater Corporation Hydrolytically degradable carbamate derivatives of poly (ethylene glycol)
ATE424413T1 (de) 2000-06-16 2009-03-15 Lilly Co Eli Analoge des glucagon-ähnlichen peptids-1
US6436386B1 (en) 2000-11-14 2002-08-20 Shearwater Corporation Hydroxyapatite-targeting poly (ethylene glycol) and related polymers
BR0116024A (pt) 2000-12-07 2005-12-13 Lilly Co Eli Proteìna de fusão heteróloga e uso da mesma
EP1351984A2 (en) 2000-12-13 2003-10-15 Eli Lilly And Company Amidated glucagon-like peptide-1
EP1411968B1 (en) * 2001-07-31 2008-09-17 THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES Glp-1 exendin-4 peptide analogs and uses thereof
CA2458371A1 (en) 2001-08-23 2003-03-06 Eli Lilly And Company Glucagon-like peptide-1 analogs
US20040235726A1 (en) 2001-10-01 2004-11-25 Jakubowski Joseph Anthony Glucagon-like peptides (glp-1) and treatment of respiratory distress
MXPA04006679A (es) 2002-01-08 2004-11-10 Lilly Co Eli Analogos extendidos de peptido-1 de tipo glucagon.
US20030232761A1 (en) * 2002-03-28 2003-12-18 Hinke Simon A. Novel analogues of glucose-dependent insulinotropic polypeptide
IL164266A0 (en) * 2002-04-10 2005-12-18 Lilly Co Eli Treatment of gastroparesis
AU2003239478A1 (en) 2002-06-04 2003-12-22 Eli Lilly And Company Modified glucagon-like peptide-1 analogs
JP2006501820A (ja) 2002-09-06 2006-01-19 バイエル・フアーマシユーチカルズ・コーポレーシヨン 修飾ｇｌｐ−１受容体アゴニストおよびそれらの薬理学的使用法
EP1567178A4 (en) 2002-11-01 2009-07-15 Amgen Inc MODULATORS OF RECEPTORS FOR NEUTRAL THERAPY HORMONE AND SIDE-HORSE HORMONE-RELATED PROTEINS
US20050059605A1 (en) * 2003-01-31 2005-03-17 Krishna Peri Chemically modified metabolites of regulatory peptides and methods of producing and using same
JP2007524579A (ja) 2003-02-19 2007-08-30 ソシエテ・ドゥ・コンセイユ・ドゥ・ルシェルシュ・エ・ダプリカーション・シャンティフィック・エス・ア・エス Ｇｌｐ−１の類似体
EP1605897B1 (en) * 2003-03-19 2012-07-25 Eli Lilly And Company Polyethelene glycol link glp-1 compounds
MXPA05013565A (es) 2003-06-12 2006-03-09 Lilly Co Eli Proteinas de fusion analogas al glp-1.
US20070253966A1 (en) 2003-06-12 2007-11-01 Eli Lilly And Company Fusion Proteins
JP2007537981A (ja) * 2003-09-19 2007-12-27 ノボ　ノルディスク　アクティーゼルスカブ 新規の血漿タンパク質親和性タグ
KR101241862B1 (ko) * 2003-09-19 2013-03-13 노보 노르디스크 에이/에스 신규 ｇｌｐ-1 유도체
WO2005035761A1 (en) * 2003-10-16 2005-04-21 Compugen Ltd. Splice variants of preproglucagon, glucagon-like peptide-1 and oxyntomodulin
US7605120B2 (en) 2003-10-22 2009-10-20 Amgen Inc. Antagonists of the brandykinin B1 receptor
MXPA06006745A (es) * 2003-12-18 2006-08-18 Novo Nordisk As Compuestos glp-1 novedosos.

Also Published As

Publication number Publication date
CA2648936A1 (en) 2007-11-01
US20130203659A1 (en) 2013-08-08
AU2007240313B2 (en) 2012-02-02
JP2012116864A (ja) 2012-06-21
EP2573111A1 (en) 2013-03-27
WO2007124461A2 (en) 2007-11-01
US8288339B2 (en) 2012-10-16
US20100048468A1 (en) 2010-02-25
MX2008013304A (es) 2008-10-27
JP2009534423A (ja) 2009-09-24
EP2007804A2 (en) 2008-12-31
CA2648936C (en) 2013-07-09
EP2574624A1 (en) 2013-04-03
WO2007124461A8 (en) 2013-12-05
EP2007804B1 (en) 2014-06-18
WO2007124461A3 (en) 2008-06-05
AU2007240313A1 (en) 2007-11-01
CA2800389A1 (en) 2007-11-01

Similar Documents

Publication Publication Date Title
ES2495741T3 (es) Compuestos de GLP-1
JP6862493B2 (ja) 新規なオキシントモジュリン誘導体及びそれを含む肥満治療用組成物
KR102544419B1 (ko) 글루카곤 및 glp-1 공-효능제 화합물
EP3368061B1 (en) Glucagon receptor agonists
ES2444622T3 (es) Derivado peptídico insulinotrópico en el que se ha modificado su aminoácido N-terminal
US20090036364A1 (en) Gip analog and hybrid polypeptides with selectable properties
RS53505B1 (sr) Peptidni analog oksintomodulina
AU2010341650A1 (en) Oxyntomodulin peptide analogue
CN102105159A (zh) 基于gip的混合激动剂用于治疗代谢紊乱和肥胖症
WO2021163972A1 (zh) Glp-1激动多肽化合物及其盐与合成方法及用途
ES2973986T3 (es) Análogo peptídico acilado de oxintomodulina
KR20230120134A (ko) 폴리펩티드 및 이의 용도
RU2673179C2 (ru) Производное инсулинотропного пептида с модифицированным N-концевым зарядом
US20150299287A1 (en) O-linked carbohydrate-modified insulin analogues
US10118954B2 (en) Apelin analogues
KR20160075825A (ko) 중증 저혈당증의 치료를 위한 신규 화합물
CA3162245C (en) Incretin analogs and uses thereof
RU2011131714A (ru) Аналоги glp-1 и их использования
HK1192261B (zh) 新型泌酸调节肽衍生物和包含该泌酸调节肽衍生物的用於治疗肥胖的药物组合物
HK1192261A (en) Novel oxyntomodulin derivatives and pharmaceutical composition for treating obesity comprising the same