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AR096927A1 - INHIBIDORES POTENTES Y SELECTIVOS DE NaV1.7 - Google Patents

INHIBIDORES POTENTES Y SELECTIVOS DE NaV1.7

Info

Publication number
AR096927A1
AR096927A1 ARP140100912A ARP140100912A AR096927A1 AR 096927 A1 AR096927 A1 AR 096927A1 AR P140100912 A ARP140100912 A AR P140100912A AR P140100912 A ARP140100912 A AR P140100912A AR 096927 A1 AR096927 A1 AR 096927A1
Authority
AR
Argentina
Prior art keywords
residue
amino acid
nal
secys
cys
Prior art date
Application number
ARP140100912A
Other languages
English (en)
Inventor
Wanska Malgorzata
M Tegley Christopher
R Falsey James
M Doherty Elizabeth
P Miranda Leslie
Biswas Kaustav
C Long Jason
K Murray Justin
Ryan Holder Jerry
Sham Kelvin
Wu Bin
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
Publication of AR096927A1 publication Critical patent/AR096927A1/es

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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
    • C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
    • C07K14/43513—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from arachnidae
    • C07K14/43518—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from arachnidae from spiders
    • 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
    • A61K47/56—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • 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
    • A61K47/68—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 an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • 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
    • A61K47/68—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 an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • A61K47/6817—Toxins
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/44—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, 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

Landscapes

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

Abstract

Se describe una composición de la materia, la cual comprende un polipéptido aislado, el cual es un inhibidor de NaV1.7 restringido periféricamente. En algunas realizaciones que se dan a conocer, el polipéptido aislado es un inhibidor de NaV1.7. Otras realizaciones son realizaciones conjugadas de la composición de la materia de la solicitud y composiciones farmacéuticas que contienen la composición de la materia de la solicitud. Se dan a conocer ácidos nucleicos aislados que codifican algunas realizaciones de polipéptidos y vectores de expresión de la solicitud, así como células huésped recombinantes que los contienen. También se da a conocer un método para tratar o prevenir el dolor. Reivindicación 1: Una composición de Ia materia, la cual comprende un polipéptido aislado que comprende la secuencia de aminoácidos de fórmula: Xaa¹Xaa²Xaa³Xaa⁴Xaa⁵Xaa⁶Xaa⁷Xaa⁸Xaa⁹Xaa¹⁰Xaa¹¹Asp¹²Xaa¹³Xaa¹⁴Xaa¹⁵Xaa¹⁶Xaa¹⁷Xaa¹⁸Xaa¹⁹Xaa²⁰Leu²¹Xaa²²Xaa²³Xaa²⁴Xaa²⁵Xaa²⁶Xaa²⁷Xaa²⁸Xaa²⁹Xaa³⁰Xaa³¹Xaa³²Xaa³³Xaa³⁴ // SEQ. ID Nº 590 o una sal farmacéuticamente aceptable del mismo, en donde: Xaa¹Xaa² está ausente; o Xaa¹ es cualquier residuo aminoacídico y Xaa² es cualquier residuo aminoacídico; o Xaa¹ está ausente y Xaa² es cualquier residuo aminoacídico; o Xaa¹ está ausente y Xaa² está ausente; Xaa³ es cualquier residuo aminoacídico; Xaa⁴ es Cys, si Xaa¹⁸ es Cys; o Xaa⁴ es SeCys, si Xaa¹⁸ es SeCys; Xaa⁵ es cualquier residuo aminoacídico hidrofílico neutro o básico; Xaa⁶ es cualquier residuo aminoacídico básico o hidrofílico neutro; Xaa⁷ es un residuo Trp, 5-bromoTrp, 6-bromoTrp, 5-cloroTrp, 6-cloroTrp, 1-Nal, 2-Nal, tioTrp, BhPhe, 2-BrhF, 2-ClhF, 2-FhF, 2-MehF, 2-MeOhF, 3-BrhF, 3-ClhF, 3-FhF, 3-MehF, 3-MeOhF, 4-BrhF, 4-ClhF, 4-FhF, 4-Me-F, 4-MehF, 4-MeOhF; Xaa⁸ es un residuo Met, Nle, Nva, Leu, Ile, Val, o Phe; Xaa⁹ es un residuo Trp, 5-bromoTrp, 6-bromoTrp, 5-cloroTrp, 6-cloroTrp, 1-Nal, 2-Nal, o tioTrp; Xaa¹⁰ es un residuo aminoacídico básico o hidrofílico neutro, o un residuo Ala; Xaa¹¹ es Cys si Xaa²³ es Cys; o Xaa¹¹ es SeCys si Xaa²³ es SeCys; Xaa¹³ es cualquier residuo aminoacídico; Xaa¹⁴ es un residuo básico o ácido o un residuo Ala; Xaa¹⁵ es un residuo Arg o Cit; Xaa¹⁶ es cualquier residuo aminoacídico; Xaa¹⁷ es Cys si Xaa²⁷ es Cys; o Xaa¹⁷ es SeCys si Xaa²⁷ es SeCys; Xaa¹⁸ es Cys o SeCys; Xaa¹⁹ es cualquier residuo aminoacídico; Xaa²⁰ es un residuo Gly, Asp o Ala; Xaa²² es un residuo aminoacídico ácido, básico o neutro hidrofílico, o un residuo Ala o Val; Xaa²³ es un residuo Cys o SeCys; Xaa²⁴ es un residuo aminoacídico básico o neutro hidrofílico o un residuo Ala; Xaa²⁵ es un residuo hidrofóbico alifático; Xaa²⁶ es un residuo Trp, 5-bromoTrp, 6-bromoTrp, 5-cloroTrp, 6-cloroTrp, 1-Nal, 2-Nal, tioTrp, 5-fenilTrp, 5-iPrTrp, 5-etilTrp, o 5-MeTrp; Xaa²⁷ es un residuo Cys o SeCys; Xaa²⁸ es un residuo aminoacídico básico o neutro hidrofílico; Xaa²⁹ es un residuo aminoacídico básico, o un residuo Tyr o Leu; Xaa³⁰ es un residuo Ile, Trp, Tyr, 5-bromoTrp, 6-bromoTrp, 5-cloroTrp, 6-cloroTrp, 1-Nal, 2-Nal, tioTrp, 1-Nal, o 2-Nal, si Xaa²² es un residuo aminoacídico ácido; o Xaa³⁰ es un residuo aminoacídico ácido o un residuo Pro, si Xaa²² es un residuo aminoacídico básico o neutro hidrofílico o un residuo Ala o Val; Xaa³¹ es un residuo Ile, Trp, Phe, Cha, Tyr, 5-bromoTrp, 6-bromoTrp, 5-cloroTrp, 6-cloroTrp, 1-Nal, 2-Nal, tioTrp, o 4-tBu-F; cada uno de Xaa³², Xaa³³, y Xaa³⁴ esté independientemente ausente o es en forma independiente un residuo aminoacídico ácido o hidrofóbico o un residuo Ser o Gly; y en donde: si Xaa⁴ y Xaa¹⁸ son ambos residuos Cys, existe un enlace disulfuro entre el residuo Xaa⁴ y el residuo Xaa¹⁸; o si Xaa⁴ y Xaa¹⁸ son ambos residuos SeCys, existe un enlace diseleniuro entre el residuo Xaa⁴ y el residuo Xaa¹⁸; si Xaa¹¹ y Xaa²³ son ambos residuos Cys, existe un enlace disulfuro entre el residuo Xaa¹¹ y el residuo Xaa²³; o si Xaa¹¹ y Xaa²³ son ambos residuos SeCys, existe un enlace diseleniuro entre el residuo Xaa¹¹ y el residuo Xaa²³; si Xaa¹⁷ y Xaa²⁷ son ambos residuos Cys, existe un enlace disulfuro entre el residuo Xaa¹⁷ y el residuo Xaa²⁷; o si Xaa¹⁷ y Xaa²⁷ son ambos residuos SeCys, existe un enlace diseleniuro entre el residuo Xaa¹⁷ y el residuo Xaa²⁷; el residuo amino terminal está opcionalmente acetilado, biotinilado o 4-pentinoilado, o PEGilado; y el residuo carboxi terminal está opcionalmente amidado.
ARP140100912A 2013-03-12 2014-03-12 INHIBIDORES POTENTES Y SELECTIVOS DE NaV1.7 AR096927A1 (es)

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US201361778331P 2013-03-12 2013-03-12

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AR096927A1 (es) 2013-03-12 2016-02-10 Amgen Inc INHIBIDORES POTENTES Y SELECTIVOS DE NaV1.7
WO2014165277A2 (en) * 2013-03-12 2014-10-09 Amgen Inc. POTENT AND SELECTIVE INHIBITORS OF Nav1.7
CN110713530B (zh) * 2018-07-12 2023-03-24 湖南师范大学 钠通道阻断剂μ-TRTX-Ca1a作为镇痛药物的应用
US20220089663A1 (en) * 2019-01-18 2022-03-24 Memorial Sloan Kettering Cancer Center PROTEINS AND FLUOROPHORE-CONTAINING COMPOUNDS SELECTIVE FOR NaV1.7
CN111471092B (zh) * 2020-04-11 2022-10-28 湖南师范大学 一种具有Nav1.9特异激活作用的蜘蛛多肽毒素及其应用
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CN113214362B (zh) * 2021-05-18 2022-06-21 湖南百尔泰克化妆品有限公司 一种对钠通道有抑制作用的多肽及其应用
CN114805492B (zh) * 2022-03-15 2025-07-22 上海元炘执药科技有限公司 一种用于抑制电压门控钠离子通道1.4的芋螺毒素kiiia突变体及其制备方法和应用
CN114805491B (zh) * 2022-03-15 2025-10-03 青岛海洋生物医药研究院 一种芋螺毒素kiiia突变体及其制备方法和应用
CN114917324B (zh) * 2022-04-22 2025-05-30 江苏好上医生物医药有限公司 一种含虎纹毒素-iv的药物组合物及其应用
CN114957431B (zh) * 2022-06-27 2023-06-20 四川丽妍工坊生物科技有限公司 一种皮肤抗皱多肽Cj2a2、制备方法及应用
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