GB2389365A - Methods for specifically inhibiting histone deacetylase-4 - Google Patents

Methods for specifically inhibiting histone deacetylase-4 Download PDF

Info

Publication number
GB2389365A
GB2389365A GB0316313A GB0316313A GB2389365A GB 2389365 A GB2389365 A GB 2389365A GB 0316313 A GB0316313 A GB 0316313A GB 0316313 A GB0316313 A GB 0316313A GB 2389365 A GB2389365 A GB 2389365A
Authority
GB
United Kingdom
Prior art keywords
hdac
histone deacetylase
methods
inhibiting
specifically inhibiting
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.)
Withdrawn
Application number
GB0316313A
Other versions
GB0316313D0 (en
Inventor
Jeffrey M Besterman
Claire Bonfils
Soon Hyung Woo
Arkadii Vaisburg
Daniel Delorme
Marielle Fournel
Rico Lavoie
Zuomei Li
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.)
Methylgene Inc
Original Assignee
Methylgene 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 Methylgene Inc filed Critical Methylgene Inc
Publication of GB0316313D0 publication Critical patent/GB0316313D0/en
Publication of GB2389365A publication Critical patent/GB2389365A/en
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1137—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/4035—Isoindoles, e.g. phthalimide
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/711—Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
    • 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
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C07K14/4702—Regulators; Modulating activity
    • 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
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62—DNA sequences coding for fusion proteins
    • 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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y305/00—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5)
    • C12Y305/01—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5) in linear amides (3.5.1)
    • C12Y305/01098—Histone deacetylase (3.5.1.98), i.e. sirtuin deacetylase
    • 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
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
    • C07K2319/23—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a GST-tag
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/341—Gapmers, i.e. of the type ===---===
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Wood Science & Technology (AREA)
  • Biomedical Technology (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Plant Pathology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physics & Mathematics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Virology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pyridine Compounds (AREA)
  • Indole Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

This invention relates to the inhibition of histone deacetylase (HDAC) expression and enzymatic activity. The invention provides methods and reagents for inhibiting HDAC-4 and HDAC-1 by inhibiting expression at the nucleic acid level or inhibiting enzymatic activity at the protein level. Specific inhibitors are antisense oligonucleotides against HDAC-4 and HDAC-1 and trichostatin analoques.

Description

GB 2389365 A continuation (72) Inventor(s): Jeffrey M Besterman Claire
Bonfils
Soon Hyung Woo Arkadii Vaisburg Daniel Delorme Marielle Fournel Rico Lavole Zuamei Li (74) Agent and/or Address for Service: Edward Evans Barker Clifford's Inn, Fetter Lane, LONDON, EC4A 1 BZ, United Kingdom
GB0316313A 2001-01-12 2002-01-14 Methods for specifically inhibiting histone deacetylase-4 Withdrawn GB2389365A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US26152201P 2001-01-12 2001-01-12
US26167401P 2001-01-12 2001-01-12
PCT/IB2002/002002 WO2002069947A2 (en) 2001-01-12 2002-01-14 Antisense oligonucleotides and trichostatin analogue histone deacetylase-4 inhibitors against cancer

Publications (2)

Publication Number Publication Date
GB0316313D0 GB0316313D0 (en) 2003-08-13
GB2389365A true GB2389365A (en) 2003-12-10

Family

ID=26948670

Family Applications (1)

Application Number Title Priority Date Filing Date
GB0316313A Withdrawn GB2389365A (en) 2001-01-12 2002-01-14 Methods for specifically inhibiting histone deacetylase-4

Country Status (6)

Country Link
JP (1) JP2004520421A (en)
KR (1) KR20040018328A (en)
CA (1) CA2434601A1 (en)
DE (1) DE10295684T9 (en)
GB (1) GB2389365A (en)
WO (1) WO2002069947A2 (en)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6897220B2 (en) 2001-09-14 2005-05-24 Methylgene, Inc. Inhibitors of histone deacetylase
US7868204B2 (en) 2001-09-14 2011-01-11 Methylgene Inc. Inhibitors of histone deacetylase
CN1578663B (en) 2001-09-14 2011-05-25 梅特希尔基因公司 Inhibitors of histone deacetylase
GB0226855D0 (en) 2002-11-18 2002-12-24 Queen Mary & Westfield College Histone deacetylase inhibitors
WO2004110418A2 (en) * 2003-06-10 2004-12-23 Kalypsys, Inc. Carbonyl compounds as inhibitors of histone deacetylase for the treatment of disease
US7271195B2 (en) 2003-06-10 2007-09-18 Kalypsys, Inc. Carbonyl compounds as inhibitors of histone deacetylase for the treatment of disease
AU2004276337B2 (en) 2003-09-24 2009-11-12 Methylgene Inc. Inhibitors of histone deacetylase
EP1574213B1 (en) * 2004-03-11 2008-07-09 Asan Laboratories Company (Cayman), Limited Use of histone deacetylase inhibitors for increasing therapeutic gain in radiotherapy and chemotherapy
US7253204B2 (en) 2004-03-26 2007-08-07 Methylgene Inc. Inhibitors of histone deacetylase
EP1819669A2 (en) * 2004-12-09 2007-08-22 Kalypsys, Inc. Novel inhibitors of histone deacetylase for the treatment of disease
GB0509225D0 (en) 2005-05-05 2005-06-15 Chroma Therapeutics Ltd Inhibitors of enzymatic activity
GB0509223D0 (en) 2005-05-05 2005-06-15 Chroma Therapeutics Ltd Enzyme inhibitors
WO2007011626A2 (en) 2005-07-14 2007-01-25 Takeda San Diego, Inc. Histone deacetylase inhibitors
GB0518237D0 (en) 2005-09-07 2005-10-19 Angeletti P Ist Richerche Bio Therapeutic compounds
ES2452820T3 (en) 2006-04-07 2014-04-02 Methylgene, Inc. Benzamide derivatives as histone deacetylase inhibitors
GB0619753D0 (en) 2006-10-06 2006-11-15 Chroma Therapeutics Ltd Enzyme inhibitors
GB0620823D0 (en) 2006-10-19 2006-11-29 Univ London Histone deacetylase inhibitors
ES2509342T3 (en) 2006-10-30 2014-10-17 Chroma Therapeutics Limited Hydroxamates as histone deacetylase inhibitors
US8030344B2 (en) 2007-03-13 2011-10-04 Methylgene Inc. Inhibitors of histone deacetylase
GB0903480D0 (en) 2009-02-27 2009-04-08 Chroma Therapeutics Ltd Enzyme Inhibitors
US9636298B2 (en) 2014-01-17 2017-05-02 Methylgene Inc. Prodrugs of compounds that enhance antifungal activity and compositions of said prodrugs

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6777217B1 (en) * 1996-03-26 2004-08-17 President And Fellows Of Harvard College Histone deacetylases, and uses related thereto
JP2002528391A (en) * 1998-10-19 2002-09-03 メチルジェン，インク． Modification of gene expression by combination therapy
KR20020007398A (en) * 1999-05-03 2002-01-26 추후제출 Inhibition of histone deacetylase

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
NOT YET ADVISED *

Also Published As

Publication number Publication date
WO2002069947A3 (en) 2003-10-09
GB0316313D0 (en) 2003-08-13
CA2434601A1 (en) 2002-09-12
WO2002069947A2 (en) 2002-09-12
KR20040018328A (en) 2004-03-03
DE10295684T1 (en) 2003-11-20
JP2004520421A (en) 2004-07-08
DE10295684T9 (en) 2004-10-14

Similar Documents

Publication Publication Date Title
GB2389365A (en) Methods for specifically inhibiting histone deacetylase-4
WO2003006652A3 (en) Inhibition of specific histone deacetylase isoforms
WO2004005513A3 (en) Methods for specifically inhibiting histone deacetylase-7 and 8
BR9908280A (en) Phospholipase enzyme inhibitors
BR9909242A (en) A2 phospholipase inhibitors
HK1044528A1 (en) Monoamine reuptake inhibitors for treatment of cnsdisorders.
WO2002042459A3 (en) Position dependent recognition of gnn nucleotide triplets by zinc fingers
WO2001070675A3 (en) Inhibitors of histone deacetylase
PL331598A1 (en) Derivatives of hydroxamic and carboxylic acids of mmp activity and tnf inhibiting action
GB2400219A (en) Method and apparatus for clinical trials
WO2000071703A3 (en) Inhibition of histone deacetylase
ZA9811112B (en) Hydroxamic acid derivatives as matrix metalloprotease (MMP) inhibitors.
EP1748046A3 (en) Inhibitors of histone deacetylase
MXPA04002397A (en) Inhibitors of histone deacetylase.
WO2006060382A3 (en) Use of hdac and/or dnmt inhibitors for treatment of ischemic injury
EP1389127A4 (en) Compositions and methods for reestablishing gene transcription through inhibition of dna methylation and histone deacetylase
EP1173614A4 (en) Antisense oligonucleotides comprising universal and/or degenerate bases
WO2000023567A3 (en) Promotion of self-renewal and improved gene transduction of hematopoietic stem cells by histone deacetylase inhibitors
NO20006023L (en) Cell adhesion inhibitor as well as pharmaceutical compositions containing it
WO2002053104A3 (en) Use of catecholamine reuptake inhibitors to enhance memory
WO2002050285A3 (en) Histone deacetylase-related gene and protein
WO2001009341A3 (en) Method of determining the activity of 1-deoxy-d-xylulose-5-phosphate reductoisomerase and 1-deoxy-d-xylulose-5-phosphate synthase
WO2001088124A3 (en) Method and reagent for the inhibition of erg
CY1107776T1 (en) NEW Oligo-Nucleotide Derivatives for Targeted Inhibition of Gene Expression
IL163875A0 (en) Methods, compositions, and kits for enhancing oli gonucleotide mediated nucleic acid sequence alteration using compositions comprising a histone de

Legal Events

Date Code Title Description
WAP Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1)