WO2014085471A1 - Compositions activées à l'acide pour le traitement des cancers, procédés d'utilisation et procédés de préparation - Google Patents

Compositions activées à l'acide pour le traitement des cancers, procédés d'utilisation et procédés de préparation Download PDF

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Publication number
WO2014085471A1
WO2014085471A1 PCT/US2013/072034 US2013072034W WO2014085471A1 WO 2014085471 A1 WO2014085471 A1 WO 2014085471A1 US 2013072034 W US2013072034 W US 2013072034W WO 2014085471 A1 WO2014085471 A1 WO 2014085471A1
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WO
WIPO (PCT)
Prior art keywords
compound
cancer
inhibitors
agent
certain embodiments
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US2013/072034
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English (en)
Inventor
Babak N. ALIZADEH
Kamran Tahamtanzadeh
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
PROGNOSDX HEALTH Inc
Original Assignee
PROGNOSDX HEALTH 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 PROGNOSDX HEALTH Inc filed Critical PROGNOSDX HEALTH Inc
Publication of WO2014085471A1 publication Critical patent/WO2014085471A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • 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
    • A61K47/54—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 compound
    • 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
    • A61K47/54—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 compound
    • A61K47/549—Sugars, nucleosides, nucleotides or nucleic 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
    • A61K47/645—Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the protecting group can be any protecting group recognized by those of skill.
  • the protecting group is capable of protecting the anti-cancer agent in a low pH microenvironment.
  • the protecting group is capable of protecting the anti-cancer agent below pH 7.
  • the protecting group is capable of protecting the anti-cancer agent at a pH between 6 and 7.
  • PD and/or L are capable of degrading at low pH to release the active anti-cancer agent A.
  • PD is not linked to A and can be administered prior to or simultaneously with A or another therapy to improve therapeutic effect by first neutralizing the tumor intracellular or extracellular pH.
  • anti-cancer agent A is selected from the group consisting of histone deacetylase inhibitors and histone demethylase inhibitors. In certain embodiments, anti-cancer agent A is selected from inhibitors of deacetylation at H4K16Ac, H3K18Ac, H4K12Ac or H3K9Ac, H4 5Ac, or combinations thereof.
  • the anti-cancer agent inhibits histone deacetylase activity at H4K16Ac, H3K18Ac, H4K12Ac, H4K5Ac and/or H3K9Ac. In certain embodiments, the anti-cancer agent inhibits histone demethylase activity at H3K4mel, H3K4me2, H3 4me3, H4K20me3, H3K27me2, H3K27mel, H3K27me2, H3K27me3, H3K9me3, H3K9me2, H3K9mel, H4R3me2, H3K36me2 and/or H3K79mel, or H3K79me2, or H3 79me3.
  • compositions can comprise substances other than diluents, for example a lubricant, such as magnesium stearate, or a coating intended for controlled release.
  • a lubricant such as magnesium stearate
  • Use may be made, as liquid compositions for oral administration, of solutions which are pharmaceutically acceptable, suspensions, emulsions, syrups and elixirs containing inert diluents, such as water or liquid paraffin.
  • These compositions can also comprise substances other than diluents, for example wetting, sweetening or flavoring products.
  • compositions and single unit dosage forms can take the form of solutions, suspensions, emulsion, tablets, pills, capsules, powders, sustained-release formulations and the like.
  • Oral formulation can include standard carriers such as
  • composition, shape, and type of dosage forms provided herein will typically vary depending on their use.
  • a dosage form used in the initial treatment of cancer may contain larger amounts of one or more of the active ingredients it comprises than a dosage form used in the maintenance treatment of the same cancer.
  • a parenteral dosage form may contain smaller amounts of one or more of the active ingredients it comprises than an oral dosage form used to treat the same disease or disorder.
  • the dosage of the composition or a composition provided herein administered to prevent, treat, manage, or ameliorate a disorder, or one or more symptoms thereof in a subject is a unit dose of 0.1 mg to 200 mg, 0.1 mg to 100 mg, 0.1 mg to 50 mg, 0.1 mg to 25 mg, 0.1 mg to 20 mg, 0.1 mg to 15 mg, 0.1 mg to 10 mg, 0.1 mg to 7.5 mg, 0.1 mg to 5 mg, 0.1 to 2.5 mg, 0.25 mg to 20 mg, 0.25 to 15 mg, 0.25 to 12 mg, 0.25 to 10 mg, 0.25 mg to 7.5 mg, 0.25 mg to 5 mg, 0.5 mg to 2.5 mg, 1 mg to 20 mg, 1 mg to 15 mg, 1 mg to 12 mg, 1 mg to 10 mg, 1 mg to 7.5 mg, 1 mg to 5 mg, or 1 mg to 2.5 mg.
  • the compounds and compositions provided herein are useful in methods of treatment of a cancer, that comprise further administration of a second agent effective for the treatment of the cancer in a subject in need thereof.
  • the second agent can be any agent known to those of skill in the art to be effective for the treatment of the cancer, including those currently approved by the FDA.
  • a protecting agent in combination with one or more second anti-cancer agents.
  • the protecting agent can be any PD described herein, or a derivative thereof.
  • the second anti-cancer agent can be any anti-cancer agent known to those of skill. Examples are described herein. It is believed that the protecting agent can neutralize or reduce the acidity of a tumor
  • the methods comprise the step of selecting for cells with modulated levels of histone methylation. In certain embodiments, the methods comprise the step of selecting for cells with modulated levels of proton excretion. In certain embodiments, the methods comprise the step of selecting for cells with modulated levels of acetate excretion. In certain embodiments, the methods comprise the step of selecting for cells with modulated extracellular pH. In certain embodiments, the methods comprise selecting for a combination of two or more of the above features.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention porte sur des composés, des compositions et des procédés destinés au traitement du cancer. Dans certains modes de réalisation, les composés peuvent comprendre un groupe protecteur d'acide lié à un agent anticancéreux par un lieur facultatif.
PCT/US2013/072034 2012-11-28 2013-11-26 Compositions activées à l'acide pour le traitement des cancers, procédés d'utilisation et procédés de préparation Ceased WO2014085471A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201261730876P 2012-11-28 2012-11-28
US61/730,876 2012-11-28

Publications (1)

Publication Number Publication Date
WO2014085471A1 true WO2014085471A1 (fr) 2014-06-05

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2013/072034 Ceased WO2014085471A1 (fr) 2012-11-28 2013-11-26 Compositions activées à l'acide pour le traitement des cancers, procédés d'utilisation et procédés de préparation

Country Status (1)

Country Link
WO (1) WO2014085471A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016043874A3 (fr) * 2014-09-17 2016-07-21 Epizyme, Inc. Polythérapie pour le traitement du cancer
WO2016025635A3 (fr) * 2014-08-13 2016-08-11 Epizyme, Inc. Polythérapie pour le traitement du cancer
US10525074B2 (en) 2013-03-14 2020-01-07 Epizyme, Inc. Combination therapy for treating cancer

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EA001926B1 (ru) * 1997-06-16 2001-10-22 Мерк Энд Ко., Инк. Стабилизированные карбапенемовые полупродукты и их синтетическое применение
EA003091B1 (ru) * 1997-08-13 2002-12-26 Авеция Лимитед Синтез олигонуклеотидов в жидкой фазе
WO2007067417A1 (fr) * 2005-12-05 2007-06-14 Nitto Denko Corporation Conjugues acides amino-polyglutamate et procedes
US20080213813A1 (en) * 2002-05-15 2008-09-04 Osamu Nakanishi Histone deacetylase inhibitor and use thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EA001926B1 (ru) * 1997-06-16 2001-10-22 Мерк Энд Ко., Инк. Стабилизированные карбапенемовые полупродукты и их синтетическое применение
EA003091B1 (ru) * 1997-08-13 2002-12-26 Авеция Лимитед Синтез олигонуклеотидов в жидкой фазе
US20080213813A1 (en) * 2002-05-15 2008-09-04 Osamu Nakanishi Histone deacetylase inhibitor and use thereof
WO2007067417A1 (fr) * 2005-12-05 2007-06-14 Nitto Denko Corporation Conjugues acides amino-polyglutamate et procedes

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KANWAL RAJNEE ET AL.: "Epigenetics and cancer.", J APPL PHYSIOL, vol. 109, 4 March 2010 (2010-03-04), pages 598 - 605 *
MARKS P.A. ET AL.: "Histone Deacetylase Inhibitors: Potential in Cancer Therapy.", J CELL BIOCHEM, vol. 107, no. 4, 1 July 2009 (2009-07-01), pages 600 - 608 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10525074B2 (en) 2013-03-14 2020-01-07 Epizyme, Inc. Combination therapy for treating cancer
WO2016025635A3 (fr) * 2014-08-13 2016-08-11 Epizyme, Inc. Polythérapie pour le traitement du cancer
WO2016043874A3 (fr) * 2014-09-17 2016-07-21 Epizyme, Inc. Polythérapie pour le traitement du cancer

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