CA2294764A1 - Inhibitors of nf-kappab as activators of hsf and inducers of heat shock proteins - Google Patents
Inhibitors of nf-kappab as activators of hsf and inducers of heat shock proteins Download PDFInfo
- Publication number
- CA2294764A1 CA2294764A1 CA002294764A CA2294764A CA2294764A1 CA 2294764 A1 CA2294764 A1 CA 2294764A1 CA 002294764 A CA002294764 A CA 002294764A CA 2294764 A CA2294764 A CA 2294764A CA 2294764 A1 CA2294764 A1 CA 2294764A1
- Authority
- CA
- Canada
- Prior art keywords
- hsf
- pharmaceutically acceptable
- mixtures
- acceptable derivatives
- corresponding pharmaceutically
- 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.)
- Abandoned
Links
- 239000003112 inhibitor Substances 0.000 title claims abstract description 28
- 239000012190 activator Substances 0.000 title claims abstract description 7
- 239000000411 inducer Substances 0.000 title claims description 15
- 102000002812 Heat-Shock Proteins Human genes 0.000 title description 9
- 108010004889 Heat-Shock Proteins Proteins 0.000 title description 9
- 108010057466 NF-kappa B Proteins 0.000 claims abstract description 44
- 102000003945 NF-kappa B Human genes 0.000 claims abstract description 44
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 23
- 238000013518 transcription Methods 0.000 claims abstract description 18
- 230000035897 transcription Effects 0.000 claims abstract description 18
- 150000001875 compounds Chemical class 0.000 claims abstract description 17
- 101150031823 HSP70 gene Proteins 0.000 claims abstract description 16
- 230000000840 anti-viral effect Effects 0.000 claims abstract description 16
- 101100125027 Dictyostelium discoideum mhsp70 gene Proteins 0.000 claims abstract description 14
- 101150052825 dnaK gene Proteins 0.000 claims abstract description 14
- 230000035939 shock Effects 0.000 claims abstract description 13
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- 238000004519 manufacturing process Methods 0.000 claims abstract description 9
- 230000003110 anti-inflammatory effect Effects 0.000 claims abstract description 7
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- 238000013519 translation Methods 0.000 claims abstract description 7
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- 230000004913 activation Effects 0.000 claims description 32
- MTCFGRXMJLQNBG-UHFFFAOYSA-N serine Chemical compound OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 20
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- MQUQNUAYKLCRME-INIZCTEOSA-N N-tosyl-L-phenylalanyl chloromethyl ketone Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N[C@H](C(=O)CCl)CC1=CC=CC=C1 MQUQNUAYKLCRME-INIZCTEOSA-N 0.000 claims description 10
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims 13
- 239000003443 antiviral agent Substances 0.000 claims 4
- 102000035195 Peptidases Human genes 0.000 claims 1
- 108050008339 Heat Shock Transcription Factor Proteins 0.000 description 40
- 102000000039 Heat Shock Transcription Factor Human genes 0.000 description 40
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- 230000015572 biosynthetic process Effects 0.000 description 13
- 238000003786 synthesis reaction Methods 0.000 description 13
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- 101710178376 Heat shock 70 kDa protein Proteins 0.000 description 12
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- 230000005764 inhibitory process Effects 0.000 description 11
- 208000015181 infectious disease Diseases 0.000 description 10
- RDFCSSHDJSZMTQ-ZDUSSCGKSA-N Tos-Lys-CH2Cl Chemical compound CC1=CC=C(S(=O)(=O)N[C@@H](CCCCN)C(=O)CCl)C=C1 RDFCSSHDJSZMTQ-ZDUSSCGKSA-N 0.000 description 9
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- 101100016370 Danio rerio hsp90a.1 gene Proteins 0.000 description 2
- 101100285708 Dictyostelium discoideum hspD gene Proteins 0.000 description 2
- 102100039337 NF-kappa-B inhibitor alpha Human genes 0.000 description 2
- 101710083073 NF-kappa-B inhibitor alpha Proteins 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 101100071627 Schizosaccharomyces pombe (strain 972 / ATCC 24843) swo1 gene Proteins 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
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- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- BZKFMUIJRXWWQK-UHFFFAOYSA-N Cyclopentenone Chemical compound O=C1CCC=C1 BZKFMUIJRXWWQK-UHFFFAOYSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 101100451497 Dictyostelium discoideum hspB gene Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241001197893 Glyptemys herpesvirus Species 0.000 description 1
- 102000012215 HSC70 Heat-Shock Proteins Human genes 0.000 description 1
- 108010036652 HSC70 Heat-Shock Proteins Proteins 0.000 description 1
- 101150022862 HSC70 gene Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 1
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
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- 230000007960 cellular response to stress Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000000120 cytopathologic effect Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000006353 environmental stress Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 238000001613 nuclear run-on assay Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000031070 response to heat Effects 0.000 description 1
- PTLRDCMBXHILCL-UHFFFAOYSA-M sodium arsenite Chemical compound [Na+].[O-][As]=O PTLRDCMBXHILCL-UHFFFAOYSA-M 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 230000006656 viral protein synthesis Effects 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Transplantation (AREA)
- Virology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
- Semiconductor Integrated Circuits (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrane Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITRM97A000392 | 1997-07-01 | ||
| IT97RM000392A IT1293069B1 (it) | 1997-07-01 | 1997-07-01 | Inibitori di nf-kb come attivatori di hsf e induttori di proteine da shock termico |
| PCT/EP1998/004066 WO1999001117A2 (en) | 1997-07-01 | 1998-07-01 | Inhibitors of nf-kappab as activators of hsf and inducers of heat shock proteins |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2294764A1 true CA2294764A1 (en) | 1999-01-14 |
Family
ID=11405151
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002294764A Abandoned CA2294764A1 (en) | 1997-07-01 | 1998-07-01 | Inhibitors of nf-kappab as activators of hsf and inducers of heat shock proteins |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP1003492A2 (enrdf_load_stackoverflow) |
| JP (1) | JP2002507981A (enrdf_load_stackoverflow) |
| AU (1) | AU8854598A (enrdf_load_stackoverflow) |
| CA (1) | CA2294764A1 (enrdf_load_stackoverflow) |
| IT (1) | IT1293069B1 (enrdf_load_stackoverflow) |
| WO (1) | WO1999001117A2 (enrdf_load_stackoverflow) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1289250B1 (it) | 1996-12-13 | 1998-09-29 | Consiglio Nazionale Ricerche | Impiego di 2 ciclopenten 1-one e suoi derivati come inibitori del fattore nf-kb |
| JP2003089636A (ja) * | 2001-07-12 | 2003-03-28 | Hirofumi Kai | 熱ショック蛋白質の合成抑制及び機能抑制剤 |
| JP5697879B2 (ja) * | 2010-03-12 | 2015-04-08 | 株式会社再春館製薬所 | 熱ショックタンパク質の発現誘導剤 |
| JP2015042675A (ja) * | 2014-11-13 | 2015-03-05 | 株式会社再春館製薬所 | 熱ショックタンパク質の発現誘導剤 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4954519A (en) * | 1987-04-28 | 1990-09-04 | Georgia Tech Research Corporation | Isocoumarins with basic substituents as serine proteases inhibitors, anticoagulants and anti-inflammatory agents |
| DE4311835A1 (de) * | 1993-04-07 | 1994-10-13 | Boehringer Ingelheim Int | Verfahren zur Inhibierung der Transkription von Genen |
-
1997
- 1997-07-01 IT IT97RM000392A patent/IT1293069B1/it active IP Right Grant
-
1998
- 1998-07-01 EP EP98940106A patent/EP1003492A2/en not_active Withdrawn
- 1998-07-01 WO PCT/EP1998/004066 patent/WO1999001117A2/en active Search and Examination
- 1998-07-01 JP JP50633999A patent/JP2002507981A/ja active Pending
- 1998-07-01 AU AU88545/98A patent/AU8854598A/en not_active Abandoned
- 1998-07-01 CA CA002294764A patent/CA2294764A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO1999001117A3 (en) | 1999-04-01 |
| EP1003492A2 (en) | 2000-05-31 |
| ITRM970392A0 (enrdf_load_stackoverflow) | 1997-07-01 |
| AU8854598A (en) | 1999-01-25 |
| WO1999001117A2 (en) | 1999-01-14 |
| IT1293069B1 (it) | 1999-02-11 |
| ITRM970392A1 (it) | 1999-01-01 |
| JP2002507981A (ja) | 2002-03-12 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |