WO2001034631A2 - ANALOGUES ET MIMETIQUES PEPTIDIQUES POUVANT ETRE UTILISES IN VIVO POUR TRAITER DES MALADIES ASSOCIEES AU REPLI ANORMAL PROTEIQUE EN DEPOTS AMYLOIDES OU PSEUDO-AMYLOIDES OU LEUR PRECURSEUR PATHOLOGIQUE RICHE EN β-FEUILLE - Google Patents

ANALOGUES ET MIMETIQUES PEPTIDIQUES POUVANT ETRE UTILISES IN VIVO POUR TRAITER DES MALADIES ASSOCIEES AU REPLI ANORMAL PROTEIQUE EN DEPOTS AMYLOIDES OU PSEUDO-AMYLOIDES OU LEUR PRECURSEUR PATHOLOGIQUE RICHE EN β-FEUILLE Download PDF

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Publication number
WO2001034631A2
WO2001034631A2 PCT/US2000/030416 US0030416W WO0134631A2 WO 2001034631 A2 WO2001034631 A2 WO 2001034631A2 US 0030416 W US0030416 W US 0030416W WO 0134631 A2 WO0134631 A2 WO 0134631A2
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WO
WIPO (PCT)
Prior art keywords
ala
pro
proψ
val
asp
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Application number
PCT/US2000/030416
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English (en)
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WO2001034631A3 (fr
Inventor
Claudio Soto-Jara
Original Assignee
Axonyx, 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 Axonyx, Inc. filed Critical Axonyx, Inc.
Priority to CA002389041A priority Critical patent/CA2389041A1/fr
Priority to BR0015513-6A priority patent/BR0015513A/pt
Priority to MXPA02004468A priority patent/MXPA02004468A/es
Priority to IL14939200A priority patent/IL149392A0/xx
Priority to EA200200536A priority patent/EA004739B1/ru
Priority to KR1020027005797A priority patent/KR20020079731A/ko
Priority to EP00976928A priority patent/EP1286590A4/fr
Priority to AU14635/01A priority patent/AU781044B2/en
Priority to JP2001537342A priority patent/JP2004513873A/ja
Publication of WO2001034631A2 publication Critical patent/WO2001034631A2/fr
Publication of WO2001034631A3 publication Critical patent/WO2001034631A3/fr

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Classifications

    • 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
    • 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
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • 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
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
    • 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
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4711—Alzheimer's disease; Amyloid plaque core protein
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C07K5/0207—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)4-C(=0), e.g. 'isosters', replacing two 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated

Definitions

  • the present invention relates to peptide analogs and peptide mimetics of ⁇ -sheet
  • the present invention is a method for treating Alzheimer's and prion diseases. More particularly, the present invention is a method for treating Alzheimer's and prion disease. More particularly, the present invention is a method for treating Alzheimer's and prion disease. More particularly, the present invention is a method for treating Alzheimer's and prion disease. More particularly, the present invention is a method for treating Alzheimer's and prion disease. More particularly, the present invention is a method for treating Alzheimer's and prion disease. More particularly, the present invention is a method for treating Alzheimer's and prion disease. More particularly, the present invention is a method for treating Alzheimer's and prion disease. More particularly, the present invention is a method for treating Alzheimer's and prion disease. More particularly, the present invention is a method for treating Alzheimer's and prion disease. More particularly, the present invention is a method for treating Alzheimer's and prion disease. More particularly, the present invention is a method for treating Alzheimer's and prion disease.
  • amyloid-like deposits or precursors thereof having a pathological beta-sheet structure amyloid-like deposits or precursors thereof having a pathological beta-sheet structure.
  • protein conformational diseases include Alzheimer's disease, prion-related disorders, systemic amyloidosis, serpin-deficiency disorders, Huntington's disease and Amyotrophic
  • the conformationally modified protein may be implicated in the
  • AD Alzheimer's disease
  • AD Alzheimer's AD is the most common dementia in elderly population. It is estimated that more than
  • AD Amyloid
  • AD Alzheimer's disease
  • amyloid aggregates, known as amyloid, in brain parenchyma and cerebral vessel walls.
  • amyloid beta-peptide A ⁇
  • APP precursor protein
  • amyloid plays an important role in
  • Amyloid is a generic term that describes fibrillar aggregates that have a common
  • tinctorial properties including the ability to emit a green birefringent glow after staining
  • Alzheimer's disease involving amyloidosis, it is possible to highlight Alzheimer's disease, prion-related disorders
  • amyloid fibrils are usually composed of proteolytic fragments of normal or mutant
  • amyloid is basically a problem of protein folding, whereby a mainly
  • hydrophobicity appears to be important to induce interaction of the monomers leading to
  • the 5-residue peptide is capable of preventing the neuronal death induced
  • ⁇ -sheet breaker peptide decreased cerebral A ⁇ accumulation and completely blocked the
  • ⁇ -sheet breaker peptides have also been designed to prevent and to revert
  • PrP c PrP sc conversion, but more interestingly to revert the infectious PrP sc conformer to a
  • Short peptides have been utilized extensively as drugs in medicine (Rao et al., C.
  • the present invention is an inhibitory peptide capable of inhibiting ⁇ pleated sheet formation in amyloid ⁇ -peptide, the inhibitory peptide being a ⁇ sheet breaker peptide analog
  • the peptide is altered chemically by: (1) modifications to the N- and C-terminal ends
  • the present invention also includes an inhibitory peptide capable of inhibiting
  • peptide being a ⁇ sheet breaker peptide analog designed by chemical modification of a ⁇ sheet
  • the present invention includes a peptide mimetic with the following
  • the peptide mimetic has the following structure:
  • the peptide mimetic has the following structure:
  • the present invention also includes a method for preventing, treating, or detecting
  • FIG. 1 is a schematic representation of the peptide bond and the potential target sites
  • FIG. 2 is a graph depicting the pharmacokinetics of a 11-residue ⁇ -sheet breaker
  • FIGS. 3A and 3B are representations of the tridimensional structure of Alzheimer's
  • FIG. 4a and 4b are graphs showing the bioavailability and stability of iAB5 and Ac-
  • FIG. 5a provides a graphical comparison of A ⁇ l-40 incubated with various other
  • FIG. 5b is a graph of amyloid formation vs. the Ac-iA ⁇ 5-Am concentration.
  • FIG. 5c is a graph of amyloid formation vs. the iA ⁇ 5 concentration.
  • FIG. 6 shows a model where there is an 83% dissolution of deposits in the ventricle
  • amygdala area and a 30% dissolution of amyloid plaque in the amygdala.
  • the inhibitory peptide is capable of
  • peptide is a ⁇ sheet breaker peptide analog designed by chemical modification of a ⁇ sheet
  • This invention also includes an inhibitory peptide capable of inhibiting conformational changes in prion PrP protein associated with amyloidosis, where the inhibitory peptide is a ⁇ sheet breaker peptide analog designed by chemical modification of a
  • Fig. 1 a generalized peptide backbone is shown, where possible targets for chemical modification are highlighted.
  • the possible targets include the following: (1)
  • Natural peptides are usually degraded by the concerted action of specialized
  • Endopeptidases and unspecific exopeptidases. Endopeptidases are often present in tissues
  • Exopeptidases are generally present in blood and peripheral organs and carry out the
  • exopeptidases recognize the atoms participating in the
  • peptide mimetics are usually completely resistant to proteolytic degradation and often can be
  • ⁇ -sheet breaker analogues designed by chemical modifications of the lead peptides.
  • DAPAAPAGPAVPV also denoted as Asp Ala Pro Ala Ala Pro Ala Gly Pro Ala Val Pro
  • Alzheimer's Inhibitors Prion Inhibitors ac-Leu Pro Phe Phe Asp-am ac-Asp Ala Pro Ala Ala Pro Ala Gly Pro Ala Val Pro Val-a des-Leu Pro Phe Phe Asp-am des-Asp Ala Pro Ala Ala Pro Ala Gly Pro Ala Val Pro Val-am ac-Leu Pro Phe Phe Asp-ale ac-Asp Ala Pro Ala Ala Pro Ala Gly Pro Ala Val Pro Val-alc des-Leu Pro Phe Phe Asp-ale des-Asp Ala Pro Ala Ala Pro Ala Gly Pro Ala Val Pro Val-alc des-Leu Pro Phe Phe Asp-ale des-Asp Ala Pro Ala Ala Pro Ala Gly Pro Ala Val Pro Val-alc
  • methylation of those residues in the inhibitor peptides is expected to enhance stability and potency.
  • the D-form showed virtually no degradation in the plasma after injection for 15 minutes.
  • the peptide was radio-iodinated using standard procedures. Peptide stability was
  • endopeptidase cleavage site is after this residue by an enzyme known as
  • prolylendopepti dase prolylendopepti dase .
  • Alzheimer's Inhibitors Prion Inhibitors leu pro phe phe asp asp ala pro ala ala pro ala gly pro ala val pro val leu Pro Phe Phe asp asp Ala Pro Ala Ala Pro Ala Gly Pro Ala Val Pro val leu Pro phe Phe asp asp Ala Pro ala Ala Pro ala Gly Pro ala Val Pro val
  • Pseudopeptides or amide bond surrogates refers to peptides containing chemical modifications of some (or all) of the peptide bonds. Amide bond
  • Ala ⁇ [CH CH 2 ]Gly refers to the moiety
  • bonds to replace are those located at the end of the peptide to prevent exoprotease
  • endopeptidase cleavage site occurs after this residue by an enzyme known as
  • prolylendopeptidase Additional amide bonds that need to be protected are determined by
  • Alzheimer's Inhibitors Leu ⁇ [CH 2 CH 2 ]Pro ⁇ [CH 2 CH 2 ]Phe Phe ⁇ [CH 2 CH 2 ]Asp Leu ⁇ [CH 2 S]Pro ⁇ [CH 2 S]Phe Phe ⁇ [CH 2 S]Asp Prion inhibitors Asp ⁇ [CH 2 CH 2 ]Ala Pro ⁇ [CH 2 CH 2 ]Ala Ala Pro ⁇ [CH 2 CH 2 ]Ala Gly Pro ⁇ [CH 2 CH 2 ]Ala Val Pro ⁇ [CH 2 CH 2 ]Val
  • peptides successfully stabilized against proteolysis consist of a mixture of several types of
  • Alzheimer's Inhibitors Ac-Leu Pro ⁇ [CH 2 CH 2 ]Phe Phe Asp-Am Ac-Leu Pro ⁇ [CH 2 S]Phe Phe Asp-Am (Me)Leu Pro ⁇ [CH 2 CH 2 ]Phe Phe Asp-Am leu Pro ⁇ [CH 2 CH 2 ]Phe Phe asp leu Pro ⁇ [CH 2 S]Phe Phe asp Ac-Leu Aib Phe Phe Asp- Am (Me)Leu Aib Phe Phe Asp- Am Leu Pro ⁇ [CH 2 CH 2 ]Phe Phe asp
  • a peptide mimetic is a molecule
  • peptide mimetic has been used sometimes to describe molecules that are
  • Peptide mimetics are not derivatives of a parent peptide
  • the objective is to reconstruct the spatial position of
  • the objective is to reconstruct the position of the pharmaco-active groups using
  • the present invention is administered in an effective amount to a subject in need thereof,
  • prevention of a condition, such as Alzheimer's disease or
  • amyloidosis disorders in a subject involves administering the compound according to
  • development of a disorder or disease comprises "treatment" of the disease.
  • the invention is
  • the compound of the present invention may be administered by any means that
  • administration may be by a
  • parenteral routes including, but not limited to, subcutaneous,
  • transdermal, or buccal routes Parenteral administration can be bolus injection or by gradual
  • amyloid or amyloid-like deposits comprises either: (1) administration of an effective amount
  • the dosage administered will be dependent upon the age, sex, health, and weight of the recipient, kind of concurrent treatment, if any, frequency of
  • amyloid or amyloid-like deposits or pathological beta-sheet precursors thereof
  • dosage may be dependent on the stability of the administered compound. A less stable
  • Preparations for parenteral administration include sterile aqueous or non-aqueous
  • solutions, suspensions, and emulsions which may contain auxiliary agents or excipients
  • compositions such as tablets and capsules can be any suitable pharmaceutical compositions which are known in the art.
  • Pharmaceutical compositions such as tablets and capsules can be any suitable pharmaceutical compositions such as tablets and capsules.
  • compositions may contain suitable, unreacted, unreacted, unreacted, unreacted, unreacted, unreacted, unreacted, unreacted, unreacted, unreacted, unreacted, unreacted, unreacted, unreacted, unreacted, unreacted, unreacted, unreacted, unreacted, unreacted, unreacted, unreacted, unreacted
  • pharmaceutically acceptable carriers comprising excipients and auxiliaries which facilitate
  • Suitable pharmaceutically acceptable vehicles are well known in the art and are described for
  • formulations for intravenous administration may include sterile aqueous solutions which
  • buffers may also contain buffers, diluents and other suitable additives.
  • Suitable formulations for parenteral administration include aqueous solutions of the
  • active compounds in water-soluble form for example, water-soluble salts.
  • water-soluble salts for example, water-soluble salts.
  • Suitable lipophilic solvents or vehicles include fatty oils, for example, sesame
  • suspensions that may contain substances which increase the viscosity of the suspension
  • the suspension may also contain stabilizers.
  • amyloid-like deposits or into pathological beta-sheet-rich precursors of such deposits to be
  • Alzheimer's disease includes, but is not limited to, Alzheimer's disease, FAF, Down's syndrome, other
  • amyloidosis disorders human prion diseases, such as kuru, Creutzf el dt- Jakob Disease
  • CJD Gerstmann-Strausslet-Scheinker Syndrome
  • GSS Gerstmann-Strausslet-Scheinker Syndrome
  • neurodegenerative diseases as well as animal prion diseases such as scrapie, spongiform
  • GYLTVAAVFRG GYLTVAAVFRG, CP10: ISEVKMDAEF
  • short A ⁇ fragments such as A ⁇ 18-21, AB1- 16
  • amyloid-like deposit in the place of injection. These lesions have the same tinctorial (congo).
  • AD brain similar to that observed in AD brain, including extensive neuronal shrinkage, astrocytosis
  • peptide were precipitated in cold methanol (mix/MeOH, 4/5, v/v) for one hour at -20°C.
  • the precipitated proteins were pelleted by centrifugation (10 OOOg, 10 min, 4°C). The
  • cannula was slowly withdrawn. Following surgery the animals were placed on a heating pad
  • references cited within the references cited herein are also entirely incorporated by reference.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Neurology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Toxicology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hospice & Palliative Care (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Psychiatry (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne un peptide inhibiteur capable d'inhiber une formation de repli en β-feuille dans un β-peptide amyloïde. Ce peptide inhibiteur est un analogue peptidique de rupture de β-feuille conçu par modification chimique d'un peptide de rupture de β-feuille capable d'inhiber la formation de repli en β-feuille dans un β-peptide amyloïde. Elle concerne également un peptide inhibiteur capable d'inhiber des modifications de conformation dans la protéine PrP de type prion associé à l'amyloïdose. Ce peptide inhibiteur est un analogue peptidique de rupture de β-feuille conçu par modification chimique d'un peptide de rupture de β-feuille capable d'inhiber les modifications de conformation de la protéine PrP de type prion associée à l'amyloïdose. Elle concerne, de plus, un mimétique de peptide représenté par la formule suivante: PMiAβ5. Dans un autre mode de réalisation, ce mimétique de peptide présente la structure suivante:PMiPrP13. Dans encore un autre mode de réalisation, ce mimétique de peptide présente la structure suivante: PMiPrP5.
PCT/US2000/030416 1999-11-05 2000-11-04 ANALOGUES ET MIMETIQUES PEPTIDIQUES POUVANT ETRE UTILISES IN VIVO POUR TRAITER DES MALADIES ASSOCIEES AU REPLI ANORMAL PROTEIQUE EN DEPOTS AMYLOIDES OU PSEUDO-AMYLOIDES OU LEUR PRECURSEUR PATHOLOGIQUE RICHE EN β-FEUILLE WO2001034631A2 (fr)

Priority Applications (9)

Application Number Priority Date Filing Date Title
CA002389041A CA2389041A1 (fr) 1999-11-05 2000-11-04 Analogues et mimetiques peptidiques pouvant etre utilises in vivo pour traiter des maladies associees au repli anormal proteique en depots amyloides ou pseudo-amyloides ou leur precurseur pathologique riche en .beta.-feuille
BR0015513-6A BR0015513A (pt) 1999-11-05 2000-11-04 Análogos e miméticos de peptìdeo adequados para emprego in vivo no tratamento de doenças associadas com dobra de proteìna anormal em depósitos de amilóide, tipo amilóide ou precursor patológico rico em lâmina beta destes
MXPA02004468A MXPA02004468A (es) 1999-11-05 2000-11-04 Peptidos analogos y mimeticos adecuados para uso in vivo en el tratamiento de enfermedades asociadas con el plegamiento anormal de la proteina dentro de amiloide o depositos similares a amiloide o precursores patologicos de los mismos ricos en lamina
IL14939200A IL149392A0 (en) 1999-11-05 2000-11-04 PEPTIDE ANALOGS AND MIMETICS SUITABLE FOR IN VIVO USE IN THE TREATMENT OF DISEASES ASSOCIATED WITH ABNORMAL PROTEIN FOLDING INTO AMYLOID, AMYLOID-LIKE DEPOSITS OR β-SHEET RICH PATHOLOGICAL PRECURSOR THEREOF
EA200200536A EA004739B1 (ru) 1999-11-05 2000-11-04 ПЕПТИДНЫЕ АНАЛОГИ И МИМЕТИКИ, ПОДХОДЯЩИЕ ДЛЯ ПРИМЕНЕНИЯ IN VIVO ПРИ ЛЕЧЕНИИ ЗАБОЛЕВАНИЙ, СВЯЗАННЫХ С АНОМАЛЬНОЙ УКЛАДКОЙ БЕЛКОВ В АМИЛОИДНЫЕ ИЛИ АМИЛОИДПОДОБНЫЕ ОТЛОЖЕНИЯ, ИЛИ ИХ ПАТОЛОГИЧЕСКИЕ ПРЕДШЕСТВЕННИКИ, ОБОГАЩЕННЫЕ b-СКЛАДКАМИ
KR1020027005797A KR20020079731A (ko) 1999-11-05 2000-11-04 아밀로이드, 아밀로이드-유사 침착물, 또는 β-쉬이트가풍부한 그의 병리학적 전구체로의 비정상적 단백질 폴딩과관련된 질환의 치료에 있어서 생체내에서 사용하기에적합한 펩티드 동족체 및 유사체
EP00976928A EP1286590A4 (fr) 1999-11-05 2000-11-04 Analogues et mimetiques peptidiques pouvant etre utilises in vivo pour traiter des maladies associees au repli anormal proteique en depots amyloides ou pseudo-amyloides ou leur precurseur pathologique riche en beta-feuille
AU14635/01A AU781044B2 (en) 1999-11-05 2000-11-04 Peptide analogs and mimetics suitable for in vivo use in the treatment of diseases associated with abnormal protein folding into amyloid, amyloid-like deposits or beta-sheet rich pathological precursor thereof
JP2001537342A JP2004513873A (ja) 1999-11-05 2000-11-04 アミロイド、アミロイド様沈着物またはそれらのβ−シートリッチな病理前駆体への異常タンパク質折り畳みに関係する疾患の治療における生体内使用に適するペプチド類似物および模倣物

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US16391199P 1999-11-05 1999-11-05
US60/163,911 1999-11-05

Publications (2)

Publication Number Publication Date
WO2001034631A2 true WO2001034631A2 (fr) 2001-05-17
WO2001034631A3 WO2001034631A3 (fr) 2002-12-27

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PCT/US2000/030416 WO2001034631A2 (fr) 1999-11-05 2000-11-04 ANALOGUES ET MIMETIQUES PEPTIDIQUES POUVANT ETRE UTILISES IN VIVO POUR TRAITER DES MALADIES ASSOCIEES AU REPLI ANORMAL PROTEIQUE EN DEPOTS AMYLOIDES OU PSEUDO-AMYLOIDES OU LEUR PRECURSEUR PATHOLOGIQUE RICHE EN β-FEUILLE

Country Status (11)

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EP (1) EP1286590A4 (fr)
JP (1) JP2004513873A (fr)
KR (2) KR20020079731A (fr)
CN (1) CN1437442A (fr)
AU (1) AU781044B2 (fr)
BR (1) BR0015513A (fr)
CA (1) CA2389041A1 (fr)
EA (1) EA004739B1 (fr)
IL (1) IL149392A0 (fr)
MX (1) MXPA02004468A (fr)
WO (1) WO2001034631A2 (fr)

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002055552A2 (fr) * 2001-01-13 2002-07-18 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Analogues cycliques solubles
WO2004005336A2 (fr) * 2002-07-08 2004-01-15 Applied Research Systems Ars Holding N.V. Peptides de rupture de feuillets $g(b)
WO2004005920A2 (fr) * 2002-07-04 2004-01-15 Priontype Gmbh & Co. Kg Procede pour enrichir et pour depister des proteines prions pathologiques modifiees (prpsc)
WO2004050689A2 (fr) * 2002-12-02 2004-06-17 Applied Research Systems Ars Holding N.V. Azapeptides
WO2006122408A1 (fr) 2005-05-18 2006-11-23 Aegera Therapeutics Inc. Composes liants de domaine bir
WO2006090289A3 (fr) * 2005-02-28 2006-12-07 Alphabeta Ab Composes destines a reduire l'agregation de beta-peptide amyloide
EP1746422A1 (fr) * 2005-07-19 2007-01-24 Universita'degli Studi Di Milano Procédé d'identification d'inhibiteurs de pliage de protéine
AU2004203461B2 (en) * 2002-01-31 2009-09-03 Tel Aviv University Future Technology Development L.P. Peptides Antibodies Directed Thereagainst and Methods Using Same for Diagnosing and Treating Amyloid-Associated Diseases
US8003612B2 (en) 1997-10-08 2011-08-23 Proteotech Inc. Small peptides for the treatment of Alzheimer's disease and other beta-amyloid protein disorders
WO2013004399A1 (fr) * 2011-07-07 2013-01-10 Agency For Science, Technology And Research Produits thérapeutiques peptidiques ultra petits de rupture d'hélice alpha, anti-amyloïdogènes
US8563273B2 (en) 2002-09-06 2013-10-22 Tel Aviv University Future Technology Development L.P. Method of screening for compounds that disaggregate amyloid aggregates
US8697634B2 (en) 2002-01-31 2014-04-15 Tel Aviv University Future Technology Development L.P. Peptides and methods using same for diagnosis and treatment of amyloid-associated disease
WO2015043566A1 (fr) * 2013-09-26 2015-04-02 Forschungszentrum Jülich GmbH Peptides cycliques se liant aux bêta-amyloïdes et leur utilisation
WO2015043567A1 (fr) * 2013-09-26 2015-04-02 Forschungszentrum Jülich GmbH Peptides se liant aux bêta-amyloïdes et leur utilisation pour le traitement et le diagnostic de la maladie d'alzheimer
US9096645B2 (en) 2010-11-15 2015-08-04 Ramot At Tel-Aviv University Ltd. Dipeptide analogs for treating conditions associated with amyloid fibril formation
US11090303B2 (en) 2018-05-15 2021-08-17 Lloyd Hung Loi Tran Therapeutic agent composition and method of use, for treatment of mild congnitive impairment, depression, and psychological disorders

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WO2002055552A2 (fr) * 2001-01-13 2002-07-18 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Analogues cycliques solubles
WO2002055552A3 (fr) * 2001-01-13 2003-04-24 Fraunhofer Ges Forschung Analogues cycliques solubles
DE10101430B4 (de) * 2001-01-13 2008-10-02 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Lösliche cyclische Analoga zur Modulation der Amyloidogenese
US7342091B2 (en) 2001-01-13 2008-03-11 Fraunhofer-Gesellschaf Zur Forderung Der Angewandten Forschung E.V Soluble cyclic analogues of β amyloid peptide
US8697634B2 (en) 2002-01-31 2014-04-15 Tel Aviv University Future Technology Development L.P. Peptides and methods using same for diagnosis and treatment of amyloid-associated disease
US8993510B2 (en) 2002-01-31 2015-03-31 Tel Aviv University Future Technology Development L.P. Peptides and methods using same for diagnosis and treatment of amyloid-associated disease
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WO2004005920A3 (fr) * 2002-07-04 2004-04-29 Priontype Gmbh Procede pour enrichir et pour depister des proteines prions pathologiques modifiees (prpsc)
WO2004005920A2 (fr) * 2002-07-04 2004-01-15 Priontype Gmbh & Co. Kg Procede pour enrichir et pour depister des proteines prions pathologiques modifiees (prpsc)
WO2004005336A3 (fr) * 2002-07-08 2004-02-26 Applied Research Systems Peptides de rupture de feuillets $g(b)
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US8563273B2 (en) 2002-09-06 2013-10-22 Tel Aviv University Future Technology Development L.P. Method of screening for compounds that disaggregate amyloid aggregates
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EP2719394A1 (fr) * 2003-06-30 2014-04-16 Tel Aviv University Future Technology Development L.P. Anticorps de peptides dirigés contre ceux-ci pour diagnostiquer et traiter des maladies associées aux amyloïdes
WO2006090289A3 (fr) * 2005-02-28 2006-12-07 Alphabeta Ab Composes destines a reduire l'agregation de beta-peptide amyloide
WO2006122408A1 (fr) 2005-05-18 2006-11-23 Aegera Therapeutics Inc. Composes liants de domaine bir
EP1883627A1 (fr) * 2005-05-18 2008-02-06 Aegera Therapeutics Inc. Composes liants de domaine bir
EP1883627B1 (fr) * 2005-05-18 2018-04-18 Pharmascience Inc. Composes liants de domaine bir
WO2007009727A1 (fr) * 2005-07-19 2007-01-25 Universita' Degli Studi Di Milano Methode d'identification d'inhibiteurs de pliage de proteines
EP1746422A1 (fr) * 2005-07-19 2007-01-24 Universita'degli Studi Di Milano Procédé d'identification d'inhibiteurs de pliage de protéine
US9630989B2 (en) 2010-11-15 2017-04-25 Ramot At Tel-Aviv University Ltd. Dipeptide analogs for treating conditions associated with amyloid fibril formation
US9096645B2 (en) 2010-11-15 2015-08-04 Ramot At Tel-Aviv University Ltd. Dipeptide analogs for treating conditions associated with amyloid fibril formation
WO2013004399A1 (fr) * 2011-07-07 2013-01-10 Agency For Science, Technology And Research Produits thérapeutiques peptidiques ultra petits de rupture d'hélice alpha, anti-amyloïdogènes
JP2014524913A (ja) * 2011-07-07 2014-09-25 エージェンシー・フォー・サイエンス・テクノロジー・アンド・リサーチ 抗アミロイド形成性αヘリックス破壊性超小型ペプチド治療薬
CN105745220A (zh) * 2013-09-26 2016-07-06 于利奇研究中心有限公司 结合β淀粉状蛋白的环状肽及其用途
WO2015043567A1 (fr) * 2013-09-26 2015-04-02 Forschungszentrum Jülich GmbH Peptides se liant aux bêta-amyloïdes et leur utilisation pour le traitement et le diagnostic de la maladie d'alzheimer
WO2015043566A1 (fr) * 2013-09-26 2015-04-02 Forschungszentrum Jülich GmbH Peptides cycliques se liant aux bêta-amyloïdes et leur utilisation
US10428127B2 (en) 2013-09-26 2019-10-01 Forschungszentrum Juelich Gmbh Cyclic, amyloid beta-binding peptides and the use thereof
CN105745220B (zh) * 2013-09-26 2020-03-27 于利奇研究中心有限公司 结合β淀粉状蛋白的环状肽及其用途
EP3747454A1 (fr) 2013-09-26 2020-12-09 Forschungszentrum Jülich GmbH Peptides liants amyloïdes-bêta et leur utilisation pour le traitement et le diagnostic de la maladie d'alzheimer
EP3797787A1 (fr) * 2013-09-26 2021-03-31 Priavoid GmbH Peptides cycliques se liants aux bêta-amyloïdes et leur utilisation
US11274125B2 (en) * 2013-09-26 2022-03-15 Priavoid Gmbh Amyloid-beta-binding peptides and the use thereof for the treatment and diagnosis of Alzheimer's disease
US11090303B2 (en) 2018-05-15 2021-08-17 Lloyd Hung Loi Tran Therapeutic agent composition and method of use, for treatment of mild congnitive impairment, depression, and psychological disorders

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KR20060133114A (ko) 2006-12-22
AU781044B2 (en) 2005-05-05
CA2389041A1 (fr) 2001-05-17
AU1463501A (en) 2001-06-06
EA004739B1 (ru) 2004-08-26
EA200200536A1 (ru) 2002-12-26
JP2004513873A (ja) 2004-05-13
BR0015513A (pt) 2004-07-06
EP1286590A2 (fr) 2003-03-05
EP1286590A4 (fr) 2005-05-11
MXPA02004468A (es) 2004-09-10
CN1437442A (zh) 2003-08-20
IL149392A0 (en) 2002-11-10
WO2001034631A3 (fr) 2002-12-27
KR20020079731A (ko) 2002-10-19

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