Title:
VALPROIC ACID AND DERIVATIVES THEREOF AS HISTONE DEACETYLASE INHIBITORS
Document Type and Number:
WIPO Patent Application WO2002007722
Kind Code:
A3
Abstract:
The present invention relates to the use of the drug valproic acid and derivatives thereof as inhibitors of enzymes having histone deacetylase activity. The invention also relates to the use of those compounds for the manufacture of a medicament for the treatment of diseases which are associated with hypoacetylation of histones or in which induction of hyperacetylation has a beneficial effect for example by induction of differentiation and/or apoptosis in transformed cells.
Inventors:
GOETTLICHER MARTIN (DE)
HEINZEL THORSTEN (DE)
GRONER BERND (DE)
HERRLICH PETER (DE)
HEINZEL THORSTEN (DE)
GRONER BERND (DE)
HERRLICH PETER (DE)
Application Number:
PCT/EP2001/007704
Publication Date:
July 18, 2002
Filing Date:
July 05, 2001
Export Citation:
Assignee:
GEORG SPEYER HAUS (DE)
GOETTLICHER MARTIN (DE)
HEINZEL THORSTEN (DE)
GRONER BERND (DE)
HERRLICH PETER (DE)
GOETTLICHER MARTIN (DE)
HEINZEL THORSTEN (DE)
GRONER BERND (DE)
HERRLICH PETER (DE)
International Classes:
A61K31/19; A61P5/02; A61P35/00; G01N33/50; A61P35/02; A61P43/00; G01N33/15; G01N33/566; G01N33/574; (IPC1-7): A61K31/19; A61P35/00; A61P5/02
Domestic Patent References:
| WO1998029114A1 | 1998-07-09 | |||
| WO1996006821A1 | 1996-03-07 | |||
| WO1997011366A1 | 1997-03-27 | |||
| WO1997035990A2 | 1997-10-02 | |||
| WO1999023885A1 | 1999-05-20 |
Other References:
DATABASE BIOSIS [online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 2000, NIEDER CARSTEN ET AL: "A review of current and future treatment strategies for malignant astrocytomas in adults.", XP002188064, Database accession no. PREV200000333383
LETIZIA C ET AL: "REDUCTION OF AN ACTH SECRETING ADENOMA IN A PATIENT WITH NELSON'S SYNDROME CHRONICALLY TREATED WITH SODIUM VALPROATE", EUROPEAN JOURNAL OF INTERNAL MEDICINE, ELSEVIER, AMSTERDAM,, NL, vol. 5, no. 4, October 1994 (1994-10-01), pages 325 - 328, XP000997468, ISSN: 0953-6205
TITTLE T V ET AL: "EFFECT OF ANTIEPILEPTIC DRUGS ON GROWTH OF MURINE LYMPHOID TUMOR CELLS IN SINGLE-CELL CULTURE", EPILEPSIA, RAVEN PRESS LTD., NEW YORK, US, vol. 33, no. 4, July 1992 (1992-07-01), pages 729 - 735, XP000997403, ISSN: 0013-9580
DATABASE MEDLINE 1 January 1900 (1900-01-01), MORI H, SAIKI I, KODA A: "EFFECT OF ALPHA-MERCAPTOPROPIONYLGLYCINE (ALPHA-MPG) AND SODIUM DIPROPYLACETATE (DPA) ON ANTIBODY FORMATION (IV)", XP002166105, Database accession no. 79170906
NORDENBERG J. ET AL: "Effects of Psychotropic Drugs on Cell Proliferation and Differentiation", BIOCHEMICAL PHARMACOLOGY, vol. 58, 1999, pages 1229 - 1236, XP001027786
SKLADCHIKOVA G ET AL: "VALPROIC ACID, BUT NOT ITS NON-TERATOGENIC ANALOGUE 2-ISOPROPYLPENTANOIC ACID, AFFECTS PROLIFERATION, VIABILITY AND NEURONAL DIFFERENTIATION OF THE HUMAN TERATOCARCINOMA CELL LINE NTERA-2", NEUROTOXICOLOGY, TOX PRESS, RADFIELD, AR, IN, vol. 19, no. 3, June 1998 (1998-06-01), pages 357 - 370, XP000997593, ISSN: 0161-813X
FISCHKOFF S A ET AL: "INDUCTION OF NEUTROPHILIC DIFFERENTIATION OF HUMAN PROMYELOCYTIC LEUKEMIC CELLS BY BRANCHED-CHAIN CARBOXYLIC ACID ANTICONVULSANT DRUGS", JOURNAL OF BIOLOGICAL RESPONSE MODIFIERS, RAVEN PRESS, NEW YORK, NY, US, vol. 3, no. 2, April 1984 (1984-04-01), pages 132 - 137, XP000997488, ISSN: 0732-6580
GOETTLICHER M ET AL: "Cellular actions of valproic acid and its teratogenic derivatives: activation of peroxisome proliferator activated recpetors (PPARs) and differentiation of teratocaarcinoma cells", NAUNYN-SCHMIEDEBERGS ARCHIV FUER PHAMAKOLOGIE, SUPPLEMENT, SPRINGER VERLAG, BERLIN,, DE, vol. 358, no. 4 suppl3, October 1998 (1998-10-01), pages r775, XP002166104, ISSN: 0944-5250
YOSHIDA M ET AL: "POTENT AND SPECIFIC INHIBITION OF MAMMALIAN HISTONE DEACETYLASE BOTH IN VIVO AND IN VITRO BY TRICHOSTATIN A", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY OF BIOLOGICAL CHEMISTS, BALTIMORE, MD, US, vol. 265, no. 28, 5 October 1990 (1990-10-05), pages 17174 - 17179, XP000616087, ISSN: 0021-9258
DATABASE MEDLINE [online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; WANG J F ET AL: "Differential display PCR reveals novel targets for the mood-stabilizing drug valproate including the molecular chaperone GRP78.", XP002196053, retrieved from STN Database accession no. 1999162490
DATABASE MEDLINE [online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; WLODARCZYK B C ET AL: "Valproic acid-induced changes in gene expression during neurulation in a mouse model.", XP002196054, retrieved from STN Database accession no. 97253481
DATABASE MEDLINE [online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; MANJI H K ET AL: "Modulation of CNS signal transduction pathways and gene expression by mood-stabilizing agents: therapeutic implications.", XP002196055, retrieved from STN Database accession no. 1999171393
DATABASE MEDLINE [online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; ROGIERS V ET AL: "Effects of the anticonvulsant, valproate, on the expression of components of the cytochrome-P-450-mediated monooxygenase system and glutathione S-transferases.", XP002196056, retrieved from STN Database accession no. 95361856
DATABASE MEDLINE [online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; CHEN G ET AL: "The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein bcl-2 in the CNS.", XP002196057, retrieved from STN Database accession no. 1999127956
DATABASE MEDLINE [online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; SANDS S A ET AL: "Changes in tyrosine hydroxylase mRNA expression in the rat locus coeruleus following acute or chronic treatment with valproic acid.", XP002196058, retrieved from STN Database accession no. 2000099305
LETIZIA C ET AL: "REDUCTION OF AN ACTH SECRETING ADENOMA IN A PATIENT WITH NELSON'S SYNDROME CHRONICALLY TREATED WITH SODIUM VALPROATE", EUROPEAN JOURNAL OF INTERNAL MEDICINE, ELSEVIER, AMSTERDAM,, NL, vol. 5, no. 4, October 1994 (1994-10-01), pages 325 - 328, XP000997468, ISSN: 0953-6205
TITTLE T V ET AL: "EFFECT OF ANTIEPILEPTIC DRUGS ON GROWTH OF MURINE LYMPHOID TUMOR CELLS IN SINGLE-CELL CULTURE", EPILEPSIA, RAVEN PRESS LTD., NEW YORK, US, vol. 33, no. 4, July 1992 (1992-07-01), pages 729 - 735, XP000997403, ISSN: 0013-9580
DATABASE MEDLINE 1 January 1900 (1900-01-01), MORI H, SAIKI I, KODA A: "EFFECT OF ALPHA-MERCAPTOPROPIONYLGLYCINE (ALPHA-MPG) AND SODIUM DIPROPYLACETATE (DPA) ON ANTIBODY FORMATION (IV)", XP002166105, Database accession no. 79170906
NORDENBERG J. ET AL: "Effects of Psychotropic Drugs on Cell Proliferation and Differentiation", BIOCHEMICAL PHARMACOLOGY, vol. 58, 1999, pages 1229 - 1236, XP001027786
SKLADCHIKOVA G ET AL: "VALPROIC ACID, BUT NOT ITS NON-TERATOGENIC ANALOGUE 2-ISOPROPYLPENTANOIC ACID, AFFECTS PROLIFERATION, VIABILITY AND NEURONAL DIFFERENTIATION OF THE HUMAN TERATOCARCINOMA CELL LINE NTERA-2", NEUROTOXICOLOGY, TOX PRESS, RADFIELD, AR, IN, vol. 19, no. 3, June 1998 (1998-06-01), pages 357 - 370, XP000997593, ISSN: 0161-813X
FISCHKOFF S A ET AL: "INDUCTION OF NEUTROPHILIC DIFFERENTIATION OF HUMAN PROMYELOCYTIC LEUKEMIC CELLS BY BRANCHED-CHAIN CARBOXYLIC ACID ANTICONVULSANT DRUGS", JOURNAL OF BIOLOGICAL RESPONSE MODIFIERS, RAVEN PRESS, NEW YORK, NY, US, vol. 3, no. 2, April 1984 (1984-04-01), pages 132 - 137, XP000997488, ISSN: 0732-6580
GOETTLICHER M ET AL: "Cellular actions of valproic acid and its teratogenic derivatives: activation of peroxisome proliferator activated recpetors (PPARs) and differentiation of teratocaarcinoma cells", NAUNYN-SCHMIEDEBERGS ARCHIV FUER PHAMAKOLOGIE, SUPPLEMENT, SPRINGER VERLAG, BERLIN,, DE, vol. 358, no. 4 suppl3, October 1998 (1998-10-01), pages r775, XP002166104, ISSN: 0944-5250
YOSHIDA M ET AL: "POTENT AND SPECIFIC INHIBITION OF MAMMALIAN HISTONE DEACETYLASE BOTH IN VIVO AND IN VITRO BY TRICHOSTATIN A", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY OF BIOLOGICAL CHEMISTS, BALTIMORE, MD, US, vol. 265, no. 28, 5 October 1990 (1990-10-05), pages 17174 - 17179, XP000616087, ISSN: 0021-9258
DATABASE MEDLINE [online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; WANG J F ET AL: "Differential display PCR reveals novel targets for the mood-stabilizing drug valproate including the molecular chaperone GRP78.", XP002196053, retrieved from STN Database accession no. 1999162490
DATABASE MEDLINE [online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; WLODARCZYK B C ET AL: "Valproic acid-induced changes in gene expression during neurulation in a mouse model.", XP002196054, retrieved from STN Database accession no. 97253481
DATABASE MEDLINE [online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; MANJI H K ET AL: "Modulation of CNS signal transduction pathways and gene expression by mood-stabilizing agents: therapeutic implications.", XP002196055, retrieved from STN Database accession no. 1999171393
DATABASE MEDLINE [online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; ROGIERS V ET AL: "Effects of the anticonvulsant, valproate, on the expression of components of the cytochrome-P-450-mediated monooxygenase system and glutathione S-transferases.", XP002196056, retrieved from STN Database accession no. 95361856
DATABASE MEDLINE [online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; CHEN G ET AL: "The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein bcl-2 in the CNS.", XP002196057, retrieved from STN Database accession no. 1999127956
DATABASE MEDLINE [online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; SANDS S A ET AL: "Changes in tyrosine hydroxylase mRNA expression in the rat locus coeruleus following acute or chronic treatment with valproic acid.", XP002196058, retrieved from STN Database accession no. 2000099305
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