DK2320927T3 - Modificerede peptider som potente inhibitorer af PSD-95/NMDA-receptorinteraktionen - Google Patents

Modificerede peptider som potente inhibitorer af PSD-95/NMDA-receptorinteraktionen Download PDF

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Publication number
DK2320927T3
DK2320927T3 DK09780378.7T DK09780378T DK2320927T3 DK 2320927 T3 DK2320927 T3 DK 2320927T3 DK 09780378 T DK09780378 T DK 09780378T DK 2320927 T3 DK2320927 T3 DK 2320927T3
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Denmark
Prior art keywords
peptide
psd
pdz1
affinity
pdz2
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DK09780378.7T
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English (en)
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Anders Bach
Kristian Strømgaard
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Univ Copenhagen
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Publication of DK2320927T3 publication Critical patent/DK2320927T3/da

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/07—Tetrapeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/08—Peptides having 5 to 11 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • 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
    • 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
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70571—Receptors; Cell surface antigens; Cell surface determinants for neuromediators, e.g. serotonin receptor, dopamine receptor
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
    • C07K5/1008—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
    • C07K5/1013—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing O or S as heteroatoms, e.g. Cys, Ser
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1021—Tetrapeptides with the first amino acid being acidic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Cell Biology (AREA)
  • Toxicology (AREA)
  • Zoology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurosurgery (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Claims (16)

1. Forbindelse, som omfatter et første peptid eller peptidanalog bundet til et andet peptid eller peptidanalog ved hjælp af en linker, hvor det første og det andet peptid eller peptidanalog omfatter mindst fire amidbundne rester, som har en sekvens YTXV eller YSXV, hvor a. Y er valgt blandt E, Q og A, og b. X er valgt blandt A, Q, D, N, N-Me-A, N-Me-Q, N-Me-D og N-Me-N.
2. Forbindelse ifølge krav 1, hvor peptidet eller peptidanalogen er N-alkyleret i position P'3 i sekvensen.
3. Forbindelse ifølge krav 1-2, hvor linkeren er en PEG-linker, som omfatter 1 til 28 grupper (N=1-28) af ethylenglycol.
4. Forbindelse ifølge krav 3, hvor PEG-linkeren omfatter fra 1 til 12 grupper (N=1-12) af ethylenglycol.
5. Forbindelse ifølge et hvilket som helst af kravene 1-4, hvor peptidet eller peptidanalogen har en længde på fra 4 til 10 amidbundne rester.
6. Forbindelse ifølge et hvilket som helst af kravene 1-5, hvor peptidet er omfattet af mindst 4 L-aminosyrerester.
7. Forbindelse ifølge et hvilket som helst af kravene 1-6, hvor X er valgt blandt A, Q og D.
8. Forbindelse ifølge et hvilket som helst af kravene 2-7, hvor peptidet eller peptidanalogen er N-alkyleret med en cyclohexansubstituent og desuden omfatter en spacer-gruppe mellem substituenten og den terminale aminogruppe af peptidet eller peptidanalogen, hvor spaceren er en alkylgruppe, der fortrinsvis er valgt blandt methylen, ethylen, propylen og butylen.
9. Forbindelse ifølge et hvilket som helst af kravene 2-7, hvor peptidet eller peptidana-logen er N-alkyleret med en aromatisk substituent og desuden omfatter en spacer-gruppe mellem substituenten og den terminale aminogruppe af peptidet, hvor spaceren er en alkylgruppe, der fortrinsvis er valgt blandt methylen, ethylen, propylen og butylen.
10. Forbindelse ifølge krav 9, hvor den aromatiske substituent er en naphthalen-2-yl-gruppe.
11. Forbindelse ifølge krav 9 eller 10, hvor den aromatiske substituent er en aromatisk ring, der er substitueret med én eller to halogen- og/eller alkylgrupper.
12. Forbindelse ifølge et hvilket som helst af kravene1-11, hvor peptidet eller peptid-analogen er kovalent bundet til en polyamin eller en diamin.
13. Forbindelse ifølge et hvilket som helst af kravene 1-12, hvor forbindelsen er valgt fra gruppen bestående af:
(83) (78) (77)
(76) (74)
(79) (80) (88)
(90) (75)
14. Farmaceutisk præparat, som omfatter en forbindelse ifølge et hvilket som helst af kravene 1-13 til anvendelse som lægemiddel.
15. Farmaceutisk præparat, som omfatter en forbindelse ifølge et hvilket som helst af kravene 1-14 til anvendelse til profylakse og/eller behandling afen excitotoxisk relateret sygdom i et individ, hvor den excitotoxiske lidelse er valgt fra gruppen bestående af slagtilfælde, traumatisk hjerneskade, iskæmisk eller traumatisk skade på centralnervesystemet (CNS), rygmarvsskade, epilepsi og neurodegenerative sygdomme i CNS.
16. Kit, som omfatter et farmaceutisk præparat ifølge et hvilket som helst af kravene 14 til 15, og som desuden omfatter midler til afgivelse af præparatet til et individ.
DK09780378.7T 2008-07-09 2009-07-09 Modificerede peptider som potente inhibitorer af PSD-95/NMDA-receptorinteraktionen DK2320927T3 (da)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US7929008P 2008-07-09 2008-07-09
EP08160017 2008-07-09
US10793308P 2008-10-23 2008-10-23
PCT/EP2009/058752 WO2010004003A2 (en) 2008-07-09 2009-07-09 Modified peptides as potent inhibitors of the psd-95/nmda receptor interaction

Publications (1)

Publication Number Publication Date
DK2320927T3 true DK2320927T3 (da) 2015-09-14

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Country Status (6)

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US (2) US9241967B2 (da)
EP (1) EP2320927B1 (da)
DK (1) DK2320927T3 (da)
ES (1) ES2542522T3 (da)
PL (1) PL2320927T3 (da)
WO (1) WO2010004003A2 (da)

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US8933013B2 (en) 2007-12-05 2015-01-13 Nono Inc. Co-administration of an agent linked to an internalization peptide with an anti-inflammatory
PL2440230T3 (pl) 2009-06-10 2021-06-14 Nono Inc. Schematy leczenia do leczenia choroby neurologicznej
US9139615B2 (en) 2011-05-13 2015-09-22 University Of Copenhagen High-affinity, dimeric inhibitors of PSD-95 as efficient neuroprotectants against ischemic brain damage and for treatment of pain
AU2012257774C1 (en) * 2011-05-13 2016-11-03 Kobenhavns Universitet (University Of Copenhagen) High-affinity, dimeric inhibitors of PSD-95 as efficient neuroprotectants against ischemic brain damage and for treatment of pain
PL2723363T3 (pl) 2011-06-24 2018-12-31 Nono Inc. Leczenie skojarzone niedokrwienia
WO2015078477A1 (en) * 2013-12-01 2015-06-04 University Of Copenhagen Fatty acid derivatives of dimeric inhibitors of psd-95
CN106661126B (zh) 2014-05-28 2021-12-10 诺诺公司 TAT-NR2B9c的氯盐
US11229675B2 (en) 2016-04-27 2022-01-25 Biocells (Beijing) Biotech Co., Ltd. Therapeutic peptides for excitatory neurotoxicity-related injuries
CN108640974B (zh) * 2018-05-19 2021-07-06 上海市第一妇婴保健院 一种靶向作用Syntenin蛋白PDZ结构域的多肽及其二聚体
CA3170425A1 (en) * 2020-02-19 2021-08-26 Nono Inc. Inhibition of reperfusion injury with a psd-95 inhibitor
EP4000598A1 (en) * 2020-11-17 2022-05-25 The Boots Company plc Tetrapeptide and compositions comprising tetrapeptides
TW202306965A (zh) 2021-05-12 2023-02-16 哥本哈根大學 Ｐｓｄ－９５抑制劑及其用途
CN117126252B (zh) * 2023-09-07 2024-05-07 湖南中晟全肽生物科技股份有限公司 一种psd-95抑制剂及其用途

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US20060148711A1 (en) * 1999-05-14 2006-07-06 Arbor Vita Corporation Molecular interactions in neurons
US7510824B2 (en) * 1999-06-02 2009-03-31 Nono Inc. Method of screening peptides useful in treating traumatic injury to the brain or spinal cord
EP1443951A4 (en) * 2001-08-03 2006-05-03 Arbor Vita Corp MOLECULAR INTERACTIONS IN CELLS
WO2007140282A1 (en) 2006-05-24 2007-12-06 Peg Biosciences Peg linker compounds and biologically active conjugates thereof
JP5746468B2 (ja) 2006-07-11 2015-07-08 ノノ インコーポレイテッド 発熱を伴う脳卒中を処置する方法および組成物
US8933013B2 (en) * 2007-12-05 2015-01-13 Nono Inc. Co-administration of an agent linked to an internalization peptide with an anti-inflammatory
US9241970B2 (en) * 2011-12-13 2016-01-26 Nono Inc. Therapy for subarachnoid hemorrhage and ischemia

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Publication number Publication date
US9241967B2 (en) 2016-01-26
WO2010004003A3 (en) 2010-05-14
ES2542522T3 (es) 2015-08-06
US9902754B2 (en) 2018-02-27
PL2320927T3 (pl) 2016-02-29
US20110178022A1 (en) 2011-07-21
EP2320927B1 (en) 2015-06-10
WO2010004003A2 (en) 2010-01-14
US20160176924A1 (en) 2016-06-23
EP2320927A2 (en) 2011-05-18

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