BR112017021507A2 - métodos para a seleção de inibidores seletivos e não seletivos de fosfatase - Google Patents

métodos para a seleção de inibidores seletivos e não seletivos de fosfatase

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Publication number
BR112017021507A2
BR112017021507A2 BR112017021507-1A BR112017021507A BR112017021507A2 BR 112017021507 A2 BR112017021507 A2 BR 112017021507A2 BR 112017021507 A BR112017021507 A BR 112017021507A BR 112017021507 A2 BR112017021507 A2 BR 112017021507A2
Authority
BR
Brazil
Prior art keywords
holophosphatase
selective
bind
selectively
compound
Prior art date
Application number
BR112017021507-1A
Other languages
English (en)
Other versions
BR112017021507B1 (pt
Inventor
Bertolotti Anne
Das Indrajit
KRZYZOSIAK Agnieszka
Rousseau Adrien
Schneider Kim
Gudny Sigurdardottir Anna
Original Assignee
Medical Research Council
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
Priority claimed from GBGB1505971.0A external-priority patent/GB201505971D0/en
Priority claimed from GBGB1505975.1A external-priority patent/GB201505975D0/en
Application filed by Medical Research Council filed Critical Medical Research Council
Publication of BR112017021507A2 publication Critical patent/BR112017021507A2/pt
Publication of BR112017021507B1 publication Critical patent/BR112017021507B1/pt

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
    • C12Q1/42—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving phosphatase
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • C07C281/00—Derivatives of carbonic acid containing functional groups covered by groups C07C269/00 - C07C279/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
    • C07C281/16—Compounds containing any of the groups, e.g. aminoguanidine
    • C07C281/18—Compounds containing any of the groups, e.g. aminoguanidine the other nitrogen atom being further doubly-bound to a carbon atom, e.g. guanylhydrazones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/61—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/30—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N11/00—Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
    • C12N11/14—Enzymes or microbial cells immobilised on or in an inorganic carrier
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/914—Hydrolases (3)
    • G01N2333/916—Hydrolases (3) acting on ester bonds (3.1), e.g. phosphatases (3.1.3), phospholipases C or phospholipases D (3.1.4)

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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  • Neurosurgery (AREA)
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  • Wood Science & Technology (AREA)
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  • Proteomics, Peptides & Aminoacids (AREA)
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Abstract

a presente invenção descreve um método para descobrir inibidores seletivos de fosfatases. assim, a invenção fornece um método de triagem de um composto teste para determinar se o composto se liga uma holofosfatase de maneira seletiva ou não seletiva, compreendendo as etapas de: i) fornecimento de uma primeira holofosfatase em que a referida holofosfatase é capturada/imobilizada; ii) testar um composto teste quanto à sua capacidade de se ligar à primeira holofosfatase; iii) fornecimento de uma segunda holofosfatase em que a referida segunda holofosfatase é capturada/imobilizada; iv) testar o mesmo composto teste quanto a sua capacidade de se ligar à segunda holofosfatase; v) comparar a ligação do composto de teste à primeira holofosfatase com a ligação à referida segunda fosfatase; em que um composto que se liga a uma holofosfatase de forma seletiva irá se ligar à referida primeira holofosfatase, mas não à referida segunda holofosfatase; ou irá se ligar à referida segunda holofosfatase, mas não a referida primeira; ou em que um composto que se liga a uma holofosfatase de forma não seletiva irá se ligar a primeira holofosfatase e a segunda holofosfatase.
BR112017021507-1A 2015-04-08 2016-04-08 Uso de um inibidor seletivo ppp1r115b e de uma composição farmacêutica compreendendo o mesmo para tratar uma doença associada ao acúmulo de proteínas mal enoveladas BR112017021507B1 (pt)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
GBGB1505971.0A GB201505971D0 (en) 2015-04-08 2015-04-08 Inhibitors and their uses
GB1505975.1 2015-04-08
GB1505971.0 2015-04-08
GBGB1505975.1A GB201505975D0 (en) 2015-04-08 2015-04-08 Inhibitors and their uses
PCT/GB2016/050990 WO2016162688A1 (en) 2015-04-08 2016-04-08 Methods for selecting phosphatase selective and non-selective phosphatase inhibitors

Publications (2)

Publication Number Publication Date
BR112017021507A2 true BR112017021507A2 (pt) 2018-07-03
BR112017021507B1 BR112017021507B1 (pt) 2023-10-31

Family

ID=55759894

Family Applications (2)

Application Number Title Priority Date Filing Date
BR112017021507-1A BR112017021507B1 (pt) 2015-04-08 2016-04-08 Uso de um inibidor seletivo ppp1r115b e de uma composição farmacêutica compreendendo o mesmo para tratar uma doença associada ao acúmulo de proteínas mal enoveladas
BR112017021522-5A BR112017021522B1 (pt) 2015-04-08 2016-04-08 Composto, composição farmacêutica e usos de compostos

Family Applications After (1)

Application Number Title Priority Date Filing Date
BR112017021522-5A BR112017021522B1 (pt) 2015-04-08 2016-04-08 Composto, composição farmacêutica e usos de compostos

Country Status (15)

Country Link
US (5) US11154519B2 (pt)
EP (2) EP3280405B1 (pt)
JP (2) JP6868568B2 (pt)
KR (2) KR102572217B1 (pt)
CN (2) CN107820518B (pt)
AU (2) AU2016246099B2 (pt)
BR (2) BR112017021507B1 (pt)
CA (2) CA2982033C (pt)
DK (2) DK3280405T3 (pt)
ES (2) ES2897712T3 (pt)
HK (2) HK1250926A1 (pt)
IL (2) IL254928B (pt)
MX (2) MX2017012926A (pt)
SG (2) SG11201708249SA (pt)
WO (2) WO2016162689A1 (pt)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016162689A1 (en) 2015-04-08 2016-10-13 Medical Research Council Inhibitors and their uses
GB201709927D0 (en) * 2017-06-21 2017-08-02 Medical Res Council Biochemically defined functional and selective activity and methods for selecting selective inhibitors of holophosphatases targeting their regulatory subunits
WO2024009280A1 (en) * 2022-07-08 2024-01-11 Baylor College Of Medicine Integrated stress response inhibitors and methods of using the same

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1223492A (en) 1967-10-13 1971-02-24 American Home Prod Guanidines
US3592935A (en) * 1969-12-11 1971-07-13 Sandoz Ag Substituted benzylidene hydrazines as anti-inflammatory agents
US3982020A (en) * 1970-03-17 1976-09-21 Sandoz, Inc. Substituted benzylidene hydrazines for treating hyperglycemia, obesity and inflammation
GB1550401A (en) 1976-01-07 1979-08-15 Hexachimie Hydrazine derivatives their preparation and their use
AU7802700A (en) 1999-10-06 2001-05-10 Melacure Therapeutics Ab Guanidine derivatives and their use in the production of a medicament for blocking xanthine oxidase/dehydrogenase
GB0019357D0 (en) * 2000-08-07 2000-09-27 Melacure Therapeutics Ab Novel phenyl guanidines
US20050136444A1 (en) 2003-09-25 2005-06-23 Scully Audra L. Treating neuropathic pain with neuropeptide FF receptor 2 agonists
FR2893844B1 (fr) 2005-11-28 2008-02-01 Centre Nat Rech Scient Utilisation du guanabenz et de ses derives pour la fabrication de medicaments pour le traitement de la mucoviscidose et de maladies liees a un defaut d'adressage des proteines dans les cellules
DE602006006578D1 (de) 2006-10-04 2009-06-10 Agronomique Inst Nat Rech Chlor enthaltende Guanabenz Derivate zur Behandlung von Prionerkrankungen
EP1908464A1 (en) * 2006-10-04 2008-04-09 Centre National De La Recherche Scientifique (Cnrs) Use of chlorine guanabenz derivatives for treating polyglutamine expansion associated diseases
GB201300435D0 (en) * 2013-01-10 2013-02-27 Medical Res Council Benzylideneguanidine Derivatives and Therapeutic Use for the Treatment of Protein Misfolding Diseases
WO2014138298A1 (en) 2013-03-05 2014-09-12 University Of Chicago Treatment of demyelinating disorders
WO2015120446A1 (en) 2014-02-10 2015-08-13 California Institute Of Technology Compositions and methods for modulating sleep and wakefuleness
ES2812800T3 (es) 2014-07-02 2021-03-18 Inflectis Bioscience Nuevos usos terapéuticos de derivados de la bencilidenguanidina para el tratamiento de proteopatías
JP6621815B2 (ja) 2014-07-02 2019-12-18 インフレクティス・バイオサイエンス Ｏ−アルキル−ベンジリデングアニジン誘導体、及びミスフォールドタンパク質の蓄積と関連する障害の処置のための治療的使用
WO2016162689A1 (en) * 2015-04-08 2016-10-13 Medical Research Council Inhibitors and their uses
US20180230105A1 (en) * 2017-01-13 2018-08-16 Regents Of The University Of Minnesota Therapeutic compounds

Also Published As

Publication number Publication date
US11154519B2 (en) 2021-10-26
CN107709291B (zh) 2021-03-12
AU2016246099A1 (en) 2017-10-26
JP6868568B2 (ja) 2021-05-12
BR112017021522A2 (pt) 2018-07-03
US11337941B2 (en) 2022-05-24
IL254928A0 (en) 2017-12-31
KR20180009740A (ko) 2018-01-29
JP6882189B2 (ja) 2021-06-02
DK3280405T3 (da) 2021-09-06
EP3280404B1 (en) 2021-10-06
AU2016246099B2 (en) 2020-09-10
ES2897712T3 (es) 2022-03-02
EP3280405A1 (en) 2018-02-14
JP2018517668A (ja) 2018-07-05
US11364211B2 (en) 2022-06-21
KR20180018491A (ko) 2018-02-21
BR112017021522B1 (pt) 2024-02-06
KR102572217B1 (ko) 2023-08-28
US20200297668A1 (en) 2020-09-24
CA2982040C (en) 2023-10-31
CN107820518A (zh) 2018-03-20
DK3280404T3 (da) 2021-11-08
ES2886571T3 (es) 2021-12-20
SG11201708246TA (en) 2017-11-29
HK1250926A1 (zh) 2019-01-18
EP3280405B1 (en) 2021-07-07
US20180111896A1 (en) 2018-04-26
JP2018517402A (ja) 2018-07-05
MX2017012924A (es) 2018-08-01
US20220313628A1 (en) 2022-10-06
WO2016162689A1 (en) 2016-10-13
WO2016162688A1 (en) 2016-10-13
CA2982033C (en) 2024-01-02
US11331286B2 (en) 2022-05-17
IL254916B (en) 2021-10-31
IL254916A0 (en) 2017-12-31
MX2017012926A (es) 2017-12-20
BR112017021507B1 (pt) 2023-10-31
US20200197337A1 (en) 2020-06-25
CA2982040A1 (en) 2016-10-13
SG11201708249SA (en) 2017-11-29
HK1250929A1 (zh) 2019-01-18
IL254928B (en) 2022-01-01
KR102602998B1 (ko) 2023-11-15
AU2016246098B2 (en) 2020-09-17
US20180125801A1 (en) 2018-05-10
EP3280404A1 (en) 2018-02-14
AU2016246098A1 (en) 2017-10-26
CN107709291A (zh) 2018-02-16
CA2982033A1 (en) 2016-10-13
CN107820518B (zh) 2023-04-21

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Free format text: DE ACORDO COM O ARTIGO 229-C DA LEI NO 10196/2001, QUE MODIFICOU A LEI NO 9279/96, A CONCESSAO DA PATENTE ESTA CONDICIONADA A ANUENCIA PREVIA DA ANVISA. CONSIDERANDO A APROVACAO DOS TERMOS DO PARECER NO 337/PGF/EA/2010, BEM COMO A PORTARIA INTERMINISTERIAL NO 1065 DE 24/05/2012, ENCAMINHA-SE O PRESENTE PEDIDO PARA AS PROVIDENCIAS CABIVEIS.

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Owner name: UNITED KINGDOM RESEARCH AND INNOVATION (GB)

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