AR095986A1 - MODIFIED PROTEINS THAT REGULATE GLUCOSE IN BLOOD WITH ALTERED PROFILE OF PHARMACOLOGICAL ACTIVITY AND PREPARATION OF THE SAME - Google Patents
MODIFIED PROTEINS THAT REGULATE GLUCOSE IN BLOOD WITH ALTERED PROFILE OF PHARMACOLOGICAL ACTIVITY AND PREPARATION OF THE SAMEInfo
- Publication number
- AR095986A1 AR095986A1 ARP140101464A ARP140101464A AR095986A1 AR 095986 A1 AR095986 A1 AR 095986A1 AR P140101464 A ARP140101464 A AR P140101464A AR P140101464 A ARP140101464 A AR P140101464A AR 095986 A1 AR095986 A1 AR 095986A1
- Authority
- AR
- Argentina
- Prior art keywords
- amino acid
- arg
- absent
- seq
- chain
- Prior art date
Links
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 title 1
- 239000008280 blood Substances 0.000 title 1
- 210000004369 blood Anatomy 0.000 title 1
- 239000008103 glucose Substances 0.000 title 1
- 102000035118 modified proteins Human genes 0.000 title 1
- 108091005573 modified proteins Proteins 0.000 title 1
- 230000000144 pharmacologic effect Effects 0.000 title 1
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical class N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 abstract 13
- 102000004877 Insulin Human genes 0.000 abstract 6
- 108090001061 Insulin Proteins 0.000 abstract 6
- 241001465754 Metazoa Species 0.000 abstract 6
- 125000000539 amino acid group Chemical group 0.000 abstract 6
- 229940125396 insulin Drugs 0.000 abstract 6
- -1 D-Hyl Chemical compound 0.000 abstract 2
- 150000008574 D-amino acids Chemical class 0.000 abstract 2
- ODKSFYDXXFIFQN-SCSAIBSYSA-N D-arginine Chemical compound OC(=O)[C@H](N)CCCNC(N)=N ODKSFYDXXFIFQN-SCSAIBSYSA-N 0.000 abstract 2
- 238000000034 method Methods 0.000 abstract 2
- 210000002966 serum Anatomy 0.000 abstract 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 abstract 1
- AHLPHDHHMVZTML-SCSAIBSYSA-N D-Ornithine Chemical compound NCCC[C@@H](N)C(O)=O AHLPHDHHMVZTML-SCSAIBSYSA-N 0.000 abstract 1
- RHGKLRLOHDJJDR-SCSAIBSYSA-N D-citrulline Chemical compound OC(=O)[C@H](N)CCCNC(N)=O RHGKLRLOHDJJDR-SCSAIBSYSA-N 0.000 abstract 1
- HNDVDQJCIGZPNO-RXMQYKEDSA-N D-histidine Chemical compound OC(=O)[C@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-RXMQYKEDSA-N 0.000 abstract 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 abstract 1
- 102000035195 Peptidases Human genes 0.000 abstract 1
- 108091005804 Peptidases Proteins 0.000 abstract 1
- 239000004365 Protease Substances 0.000 abstract 1
- 230000015556 catabolic process Effects 0.000 abstract 1
- 238000006731 degradation reaction Methods 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 102000004169 proteins and genes Human genes 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
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
- C07K14/62—Insulins
- C07K14/622—Insulins at least 1 amino acid in D-form
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Diabetes (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Endocrinology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Obesity (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Emergency Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
Métodos para preparar estas moléculas, formulaciones farmacéuticas de las mismas, así como su uso en terapia. Además, la solicitud se refiere a métodos para inhibir la degradación de proteasas en suero y/o el aumento de la estabilidad en suero de una proteína. Reivindicación 1: Un análogo de insulina modificada o una sal del mismo de fórmula (1) en donde (a) A0 está ausente o es Arg, (b) (A1 - A5) son restos de aminoácidos en las posiciones A1 a A5 en la cadena A del ser humano (SEC ID Nº 1) o insulina animal, (c) (A8 - A10) son restos de aminoácidos en las posiciones A8 a A10 en la cadena A del ser humano (SEC ID Nº 1) o insulina animal, (d) (A12 - A19) son restos de aminoácidos en las posiciones A12 a A19 en la cadena A del ser humano (SEC ID Nº 1) o insulina animal, (e) A21 es Asn o Gly, (f) B1 es Phe o His, (g) B3 es Asn o His, (h) B2 y (B4 - B6) son restos de aminoácidos en las posiciones B2 y B4 a B6 en la cadena B del ser humano (SEC ID Nº 2) o insulina animal, (i) (B8 - B18) son restos de aminoácidos en las posiciones B8 a B18 en la cadena B del ser humano (SEC ID Nº 2) o insulina animal, (j) (B20 - B27) son restos de aminoácidos en las posiciones B20 a B27 en la cadena B del ser humano (SEC ID Nº 2) o insulina animal, (k) B28 es Pro o Lys, (l) B29 es Lys o está ausente, (m) B30 es Thr o está ausente, (n) B31 está ausente, es Arg o un D-aminoácido básico, particularmente D-Arg, D-His, D-Lys, D-Hyl, D-Ornitina, o D-Citrulina, (o) B32 es un D-aminoácido básico, particularmente D-Arg, con la condición de que si B31 es Arg, entonces A21 es Gly, o si B31 está ausente, entonces A0 es Arg, y con la condición de que si B28 es Lys y B29, B30 y B31 están ausentes, entonces A0 es Arg.Methods to prepare these molecules, pharmaceutical formulations thereof, as well as their use in therapy. In addition, the application relates to methods for inhibiting the degradation of serum proteases and / or increasing the stability in serum of a protein. Claim 1: A modified insulin analogue or a salt thereof of formula (1) wherein (a) A0 is absent or is Arg, (b) (A1-A5) are amino acid residues at positions A1 to A5 in the human A chain (SEQ ID No. 1) or animal insulin, (c) (A8 - A10) are amino acid residues at positions A8 to A10 in human A chain (SEQ ID No. 1) or animal insulin, (d) (A12 - A19) are amino acid residues at positions A12 to A19 in the human chain A (SEQ ID No. 1) or animal insulin, (e) A21 is Asn or Gly, (f) B1 is Phe or His, (g) B3 is Asn or His, (h) B2 and (B4-B6) are amino acid residues at positions B2 and B4 through B6 in the human B chain (SEQ ID NO: 2) or animal insulin , (i) (B8 - B18) are amino acid residues at positions B8 to B18 in the human B chain (SEQ ID No. 2) or animal insulin, (j) (B20 - B27) are amino acid residues in positions B20 to B27 in the human B chain (SEQ ID No. 2) or animal insulin , (k) B28 is Pro or Lys, (l) B29 is Lys or is absent, (m) B30 is Thr or is absent, (n) B31 is absent, is Arg or a basic D-amino acid, particularly D-Arg , D-His, D-Lys, D-Hyl, D-Ornithine, or D-Citrulline, (o) B32 is a basic D-amino acid, particularly D-Arg, with the proviso that if B31 is Arg, then A21 is Gly, or if B31 is absent, then A0 is Arg, and with the proviso that if B28 is Lys and B29, B30 and B31 are absent, then A0 is Arg.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13305431 | 2013-04-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR095986A1 true AR095986A1 (en) | 2015-11-25 |
Family
ID=48083085
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP140101464A AR095986A1 (en) | 2013-04-03 | 2014-04-01 | MODIFIED PROTEINS THAT REGULATE GLUCOSE IN BLOOD WITH ALTERED PROFILE OF PHARMACOLOGICAL ACTIVITY AND PREPARATION OF THE SAME |
Country Status (2)
| Country | Link |
|---|---|
| AR (1) | AR095986A1 (en) |
| WO (1) | WO2014161835A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3270949B1 (en) * | 2015-03-13 | 2025-01-29 | Case Western Reserve University | Insulin analogues containing a glucose-regulated conformational switch |
| JP2020097531A (en) * | 2018-12-17 | 2020-06-25 | 協同乳業株式会社 | GLP-1 secretagogue |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3327709A1 (en) * | 1983-07-29 | 1985-02-07 | Hoechst Ag, 6230 Frankfurt | INSULIN DERIVATIVE CRYSTAL SUSPENSIONS, METHOD FOR THE PRODUCTION AND USE THEREOF |
| US5514646A (en) * | 1989-02-09 | 1996-05-07 | Chance; Ronald E. | Insulin analogs modified at position 29 of the B chain |
| IL93282A (en) * | 1989-02-09 | 1995-08-31 | Lilly Co Eli | Insulin analogs |
| EP1180121B9 (en) * | 1999-05-17 | 2004-09-08 | Conjuchem, Inc. | Long lasting insulinotropic peptides |
| KR101135244B1 (en) * | 2007-11-29 | 2012-04-24 | 한미사이언스 주식회사 | A pharmaceutical composition for treating obesity-related disease comprising insulinotropic peptide conjugate |
| TWI428346B (en) | 2006-12-13 | 2014-03-01 | Imp Innovations Ltd | Novel compounds and their effects on feeding behaviour |
| JP6017754B2 (en) | 2007-02-15 | 2016-11-02 | インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションＩｎｄｉａｎａ Ｕｎｉｖｅｒｓｉｔｙ Ｒｅｓｅａｒｃｈ Ａｎｄ Ｔｅｃｈｎｏｌｏｇｙ Ｃｏｒｐｏｒａｔｉｏｎ | Glucagon / GLP-1 receptor co-agonist |
| DK2158214T3 (en) | 2007-06-15 | 2011-12-05 | Zealand Pharma As | Glucagon analogues |
| BRPI0915282A2 (en) | 2008-06-17 | 2017-02-07 | Univ Indiana Res & Tech Corp | gip-based mixed agonists for the treatment of metabolic disorders and obesity |
| AU2009260302B2 (en) | 2008-06-17 | 2014-10-23 | Indiana University Research And Technology Corporation | Glucagon/GLP-1 receptor co-agonists |
| WO2010070252A1 (en) | 2008-12-15 | 2010-06-24 | Zealand Pharma A/S | Glucagon analogues |
| JP5635531B2 (en) | 2008-12-15 | 2014-12-03 | ジーランド ファーマ アクティーゼルスカブ | Glucagon analog |
| JP5635529B2 (en) | 2008-12-15 | 2014-12-03 | ジーランド ファーマ アクティーゼルスカブ | Glucagon analog |
| NZ593813A (en) | 2008-12-15 | 2013-02-22 | Zealand Pharma As | Glucagon analogues |
| WO2010096052A1 (en) | 2009-02-19 | 2010-08-26 | Merck Sharp & Dohme Corp. | Oxyntomodulin analogs |
| US9150632B2 (en) | 2009-06-16 | 2015-10-06 | Indiana University Research And Technology Corporation | GIP receptor-active glucagon compounds |
| ME02220B (en) | 2009-07-13 | 2016-02-20 | Zealand Pharma As | Acylated glucagon analogues |
| WO2011075393A2 (en) | 2009-12-18 | 2011-06-23 | Indiana University Research And Technology Corporation | Glucagon/glp-1 receptor co-agonists |
| RU2012136450A (en) | 2010-01-27 | 2014-03-10 | Индиана Юниверсити Рисерч Энд Текнолоджи Корпорейшн | CONJUGATES GLUCAGON ANTAGONIST - GIP AGONIST AND COMPOSITIONS FOR TREATMENT OF METABOLIC DISORDERS AND OBESITY |
| AR080592A1 (en) | 2010-03-26 | 2012-04-18 | Lilly Co Eli | PEPTIDE WITH ACTIVITY FOR GIP-R AND GLP-1-R, FAMILY FORMULATION THAT UNDERSTANDS IT, ITS USE TO PREPARE A USEFUL MEDICINAL PRODUCT FOR THE TREATMENT OF MELLITUS DIABETES AND TO INDICATE WEIGHT LOSS |
| US20130143798A1 (en) | 2010-03-26 | 2013-06-06 | Novo Nordisk A/S | Novel glucagon analogues |
| JPWO2011152182A1 (en) | 2010-05-31 | 2013-07-25 | 株式会社ジェイテクト | Manufacturing method of covering member |
| CN102906981B (en) | 2010-06-01 | 2016-03-16 | 本田技研工业株式会社 | The control device of DC/DC transducer |
| AR081975A1 (en) | 2010-06-23 | 2012-10-31 | Zealand Pharma As | GLUCAGON ANALOGS |
| CA2821766A1 (en) | 2010-12-22 | 2012-06-28 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting gip receptor activity |
| DK2694095T3 (en) | 2011-04-05 | 2018-05-28 | Longevity Biotech Inc | COMPOSITIONS COMPREHENSIVE GLUCAGON ANALOGS AND METHODS FOR PREPARING AND USING THE SAME |
-
2014
- 2014-04-01 AR ARP140101464A patent/AR095986A1/en unknown
- 2014-04-01 WO PCT/EP2014/056496 patent/WO2014161835A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| WO2014161835A1 (en) | 2014-10-09 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FB | Suspension of granting procedure |