BRPI0710099A2 - uso de inibidores de quìnases jun n-terminais para tratar glaucoma - Google Patents
uso de inibidores de quìnases jun n-terminais para tratar glaucoma Download PDFInfo
- Publication number
- BRPI0710099A2 BRPI0710099A2 BRPI0710099-0A BRPI0710099A BRPI0710099A2 BR PI0710099 A2 BRPI0710099 A2 BR PI0710099A2 BR PI0710099 A BRPI0710099 A BR PI0710099A BR PI0710099 A2 BRPI0710099 A2 BR PI0710099A2
- Authority
- BR
- Brazil
- Prior art keywords
- composition
- jnk
- formula
- cells
- glaucoma
- Prior art date
Links
- 208000010412 Glaucoma Diseases 0.000 title claims abstract description 25
- 229940043355 kinase inhibitor Drugs 0.000 title abstract description 5
- 239000003757 phosphotransferase inhibitor Substances 0.000 title abstract description 5
- 239000000203 mixture Substances 0.000 claims abstract description 43
- 238000000034 method Methods 0.000 claims abstract description 31
- 239000012825 JNK inhibitor Substances 0.000 claims description 30
- 101000950669 Homo sapiens Mitogen-activated protein kinase 9 Proteins 0.000 claims description 22
- 102100037809 Mitogen-activated protein kinase 9 Human genes 0.000 claims description 22
- 230000004410 intraocular pressure Effects 0.000 claims description 18
- 238000009472 formulation Methods 0.000 claims description 16
- 229940118135 JNK inhibitor Drugs 0.000 claims description 12
- 239000003112 inhibitor Substances 0.000 claims description 9
- 230000003247 decreasing effect Effects 0.000 claims description 8
- 206010030043 Ocular hypertension Diseases 0.000 claims description 5
- 230000000699 topical effect Effects 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000009467 reduction Effects 0.000 claims description 4
- 239000003981 vehicle Substances 0.000 claims description 4
- 229940113601 irrigation solution Drugs 0.000 claims 3
- 230000007423 decrease Effects 0.000 abstract description 14
- 230000004112 neuroprotection Effects 0.000 abstract description 13
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 abstract description 4
- 102100037808 Mitogen-activated protein kinase 8 Human genes 0.000 abstract description 4
- 210000004027 cell Anatomy 0.000 description 50
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 18
- 230000000694 effects Effects 0.000 description 18
- 229930195712 glutamate Natural products 0.000 description 18
- 239000000243 solution Substances 0.000 description 14
- 230000004083 survival effect Effects 0.000 description 11
- 241000700159 Rattus Species 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 210000001328 optic nerve Anatomy 0.000 description 10
- 230000002207 retinal effect Effects 0.000 description 10
- 108010067306 Fibronectins Proteins 0.000 description 9
- 102000016359 Fibronectins Human genes 0.000 description 9
- 108010025020 Nerve Growth Factor Proteins 0.000 description 9
- 230000006907 apoptotic process Effects 0.000 description 9
- 208000028867 ischemia Diseases 0.000 description 9
- 102000007072 Nerve Growth Factors Human genes 0.000 description 8
- 108090000765 processed proteins & peptides Proteins 0.000 description 8
- 230000006378 damage Effects 0.000 description 7
- 239000001963 growth medium Substances 0.000 description 7
- 239000003900 neurotrophic factor Substances 0.000 description 7
- 230000001228 trophic effect Effects 0.000 description 7
- 208000028389 Nerve injury Diseases 0.000 description 6
- 206010038848 Retinal detachment Diseases 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 6
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 6
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 6
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 230000008764 nerve damage Effects 0.000 description 6
- 230000001681 protective effect Effects 0.000 description 6
- 230000010410 reperfusion Effects 0.000 description 6
- 230000004264 retinal detachment Effects 0.000 description 6
- 231100000419 toxicity Toxicity 0.000 description 6
- 230000001988 toxicity Effects 0.000 description 6
- 230000032258 transport Effects 0.000 description 6
- 101000628949 Homo sapiens Mitogen-activated protein kinase 10 Proteins 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 231100000673 dose–response relationship Toxicity 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- SCMLRESZJCKCTC-KMYQRJGFSA-N gtpl8173 Chemical compound C12=CC=C(CSCC)C=C2C2=C(CNC3=O)C3=C3C4=CC(CSCC)=CC=C4N4C3=C2N1[C@]1(C)[C@@](O)(C(=O)OC)C[C@H]4O1 SCMLRESZJCKCTC-KMYQRJGFSA-N 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 208000020911 optic nerve disease Diseases 0.000 description 5
- 210000001525 retina Anatomy 0.000 description 5
- 102100026931 Mitogen-activated protein kinase 10 Human genes 0.000 description 4
- 206010061323 Optic neuropathy Diseases 0.000 description 4
- 101150052863 THY1 gene Proteins 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 208000002780 macular degeneration Diseases 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 3
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 3
- 102000015225 Connective Tissue Growth Factor Human genes 0.000 description 3
- 108010039419 Connective Tissue Growth Factor Proteins 0.000 description 3
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 3
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 3
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 208000010038 Ischemic Optic Neuropathy Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 208000008589 Obesity Diseases 0.000 description 3
- 206010030348 Open-Angle Glaucoma Diseases 0.000 description 3
- 108090000526 Papain Proteins 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- 208000007014 Retinitis pigmentosa Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 210000002744 extracellular matrix Anatomy 0.000 description 3
- 208000030533 eye disease Diseases 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000000302 ischemic effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 210000005036 nerve Anatomy 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 235000020824 obesity Nutrition 0.000 description 3
- 229940055729 papain Drugs 0.000 description 3
- 235000019834 papain Nutrition 0.000 description 3
- 201000006366 primary open angle glaucoma Diseases 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 206010003497 Asphyxia Diseases 0.000 description 2
- 201000004569 Blindness Diseases 0.000 description 2
- 208000014644 Brain disease Diseases 0.000 description 2
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 2
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N Cysteine Chemical compound SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 2
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 2
- 208000003098 Ganglion Cysts Diseases 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 206010030924 Optic ischaemic neuropathy Diseases 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 208000002367 Retinal Perforations Diseases 0.000 description 2
- 206010057430 Retinal injury Diseases 0.000 description 2
- 206010038910 Retinitis Diseases 0.000 description 2
- 206010038923 Retinopathy Diseases 0.000 description 2
- 208000005400 Synovial Cyst Diseases 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 201000007058 anterior ischemic optic neuropathy Diseases 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 229960000686 benzalkonium chloride Drugs 0.000 description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 230000003412 degenerative effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000001627 detrimental effect Effects 0.000 description 2
- 230000004406 elevated intraocular pressure Effects 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 2
- 229910052753 mercury Inorganic materials 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 201000001119 neuropathy Diseases 0.000 description 2
- 230000007823 neuropathy Effects 0.000 description 2
- 231100000915 pathological change Toxicity 0.000 description 2
- 230000036285 pathological change Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 108091008695 photoreceptors Proteins 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 208000032253 retinal ischemia Diseases 0.000 description 2
- 210000001116 retinal neuron Anatomy 0.000 description 2
- 235000020046 sherry Nutrition 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000002889 sympathetic effect Effects 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- CBCKQZAAMUWICA-UHFFFAOYSA-N 1,4-phenylenediamine Chemical compound NC1=CC=C(N)C=C1 CBCKQZAAMUWICA-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- -1 BcI- Xl Proteins 0.000 description 1
- 101150017888 Bcl2 gene Proteins 0.000 description 1
- 102100030497 Cytochrome c Human genes 0.000 description 1
- 108010075031 Cytochromes c Proteins 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102100031758 Extracellular matrix protein 1 Human genes 0.000 description 1
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 101000866526 Homo sapiens Extracellular matrix protein 1 Proteins 0.000 description 1
- 101000950695 Homo sapiens Mitogen-activated protein kinase 8 Proteins 0.000 description 1
- 101000763314 Homo sapiens Thrombomodulin Proteins 0.000 description 1
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 1
- 101000938391 Homo sapiens Transmembrane protein Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 206010023644 Lacrimation increased Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 102100025207 Mitogen-activated protein kinase kinase kinase 11 Human genes 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 102000015336 Nerve Growth Factor Human genes 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 102100023132 Transcription factor Jun Human genes 0.000 description 1
- 102000011117 Transforming Growth Factor beta2 Human genes 0.000 description 1
- 101800000304 Transforming growth factor beta-2 Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- VLSMHEGGTFMBBZ-UHFFFAOYSA-N alpha-Kainic acid Natural products CC(=C)C1CNC(C(O)=O)C1CC(O)=O VLSMHEGGTFMBBZ-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000002159 anterior chamber Anatomy 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 230000005978 brain dysfunction Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000001886 ciliary effect Effects 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- OGGXGZAMXPVRFZ-UHFFFAOYSA-M dimethylarsinate Chemical compound C[As](C)([O-])=O OGGXGZAMXPVRFZ-UHFFFAOYSA-M 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940078469 dl- cysteine Drugs 0.000 description 1
- 230000003028 elevating effect Effects 0.000 description 1
- IDLVQOMJOKNXSL-UHFFFAOYSA-N ethyl 3,5-diaminobenzoate Chemical class CCOC(=O)C1=CC(N)=CC(N)=C1 IDLVQOMJOKNXSL-UHFFFAOYSA-N 0.000 description 1
- 230000003492 excitotoxic effect Effects 0.000 description 1
- 231100000063 excitotoxicity Toxicity 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 238000009650 gentamicin protection assay Methods 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 230000009390 immune abnormality Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 239000005414 inactive ingredient Substances 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- VLSMHEGGTFMBBZ-OOZYFLPDSA-N kainic acid Chemical compound CC(=C)[C@H]1CN[C@H](C(O)=O)[C@H]1CC(O)=O VLSMHEGGTFMBBZ-OOZYFLPDSA-N 0.000 description 1
- 229950006874 kainic acid Drugs 0.000 description 1
- 230000004317 lacrimation Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 1
- 108010041596 mitogen-activated protein kinase kinase kinase 11 Proteins 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000010300 motor neuron apoptotic process Effects 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 229940053128 nerve growth factor Drugs 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 230000009223 neuronal apoptosis Effects 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000004386 ocular blood flow Effects 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 238000004091 panning Methods 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 229940124606 potential therapeutic agent Drugs 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 230000001012 protector Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000003994 retinal ganglion cell Anatomy 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 230000009834 selective interaction Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000007447 staining method Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 210000001585 trabecular meshwork Anatomy 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 229940072041 transforming growth factor beta 2 Drugs 0.000 description 1
- 230000006496 vascular abnormality Effects 0.000 description 1
- 230000004382 visual function Effects 0.000 description 1
- 230000004393 visual impairment Effects 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
- 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
- A61K31/407—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 other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- 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)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Ophthalmology & Optometry (AREA)
- Bioinformatics & Cheminformatics (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)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/394,893 US7803824B2 (en) | 2004-10-29 | 2006-03-31 | Use of inhibitors of Jun N-terminal kinases to treat glaucoma |
| US11/394,893 | 2006-03-31 | ||
| PCT/US2007/063961 WO2007117849A2 (en) | 2006-03-31 | 2007-03-14 | Use of inhibitors of jun n-terminal kinases to treat glaucoma |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BRPI0710099A2 true BRPI0710099A2 (pt) | 2011-08-02 |
Family
ID=38523463
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BRPI0710099-0A BRPI0710099A2 (pt) | 2006-03-31 | 2007-03-14 | uso de inibidores de quìnases jun n-terminais para tratar glaucoma |
Country Status (13)
| Country | Link |
|---|---|
| US (3) | US7803824B2 (enExample) |
| EP (1) | EP2004158A2 (enExample) |
| JP (1) | JP5241033B2 (enExample) |
| KR (1) | KR20080108503A (enExample) |
| CN (1) | CN101415407B (enExample) |
| AR (1) | AR060222A1 (enExample) |
| AU (1) | AU2007235111B2 (enExample) |
| BR (1) | BRPI0710099A2 (enExample) |
| CA (1) | CA2644721A1 (enExample) |
| MX (1) | MX2008011319A (enExample) |
| TW (1) | TWI419694B (enExample) |
| WO (1) | WO2007117849A2 (enExample) |
| ZA (1) | ZA200807667B (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7803824B2 (en) * | 2004-10-29 | 2010-09-28 | Alcon, Inc. | Use of inhibitors of Jun N-terminal kinases to treat glaucoma |
| US20060094753A1 (en) * | 2004-10-29 | 2006-05-04 | Alcon, Inc. | Use of inhibitors of Jun N-terminal kinases for the treatment of glaucomatous retinopathy and ocular diseases |
| US20090202524A1 (en) * | 2007-10-31 | 2009-08-13 | Alcon Research, Ltd. | Pai-1 expression and activity inhibitors for the treatment of ocular disorders |
| US20100056609A1 (en) * | 2008-08-26 | 2010-03-04 | Washington University | Methods and compositions for inhibition of axonal degeneration by modulation of the dlk/jnk pathway |
| WO2010151638A1 (en) * | 2009-06-25 | 2010-12-29 | Medical College Of Georgia Research Institute, Inc. | Jnk inhibitors for use in treating spinal muscular atrophy |
| JP2014511391A (ja) * | 2011-03-07 | 2014-05-15 | フォンダッツィオーネ・テレソン | Ｔｆｅｂリン酸化阻害剤およびその使用 |
| AU2014301631A1 (en) * | 2013-06-26 | 2015-08-27 | Xigen Inflammation Ltd. | New use of cell-permeable peptide inhibitors of the JNK signal transduction pathway for the treatment of various diseases |
| AU2015281361A1 (en) * | 2014-06-26 | 2016-11-17 | Xigen Inflammation Ltd. | New use of cell-permeable peptide inhibitors of the JNK signal transduction pathway for the treatment of various diseases |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997040847A1 (en) * | 1996-04-26 | 1997-11-06 | University Of Ottawa | Therapeutic and drug screening methods for the treatment and prevention of neuronal disease |
| KR20010083884A (ko) | 1998-10-13 | 2001-09-03 | 세파론, 인코포레이티드 | 눈 질환 치료제 |
| ATE253062T1 (de) | 1998-12-17 | 2003-11-15 | Hoffmann La Roche | 4- und 5-alkynyloxindole sowie 4- und 5- alkenyloxindole |
| EP1175399B1 (en) | 1999-04-23 | 2009-03-11 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-jun n-terminal kinases (jnk) |
| CZ2002534A3 (cs) | 1999-08-13 | 2002-07-17 | Vertex Pharmaceuticals Incorporated | Inhibitory protein-kináz, farmaceutické prostředky, které je obsahují, a jejich pouľití |
| US20040072888A1 (en) * | 1999-08-19 | 2004-04-15 | Bennett Brydon L. | Methods for treating inflammatory conditions or inhibiting JNK |
| CN1304375C (zh) | 1999-08-19 | 2007-03-14 | 信号药品公司 | 用作jnk抑制剂的吡唑并蒽酮及其衍生物和它们的组合物 |
| EP1088815A1 (en) | 1999-09-28 | 2001-04-04 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active sulfonyl amino acid derivatives |
| EP1088822A1 (en) | 1999-09-28 | 2001-04-04 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active sulfonyl hydrazide derivatives |
| EP1088821A1 (en) | 1999-09-28 | 2001-04-04 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active sulfonamide derivatives |
| EP1110957A1 (en) | 1999-12-24 | 2001-06-27 | Applied Research Systems ARS Holding N.V. | Benzazole derivatives and their use as JNK modulators |
| EP1289523A1 (en) | 2000-06-01 | 2003-03-12 | Merck & Co., Inc. | Use of (di-substituted-phenyl)-pyrimidinyl-imidazole derivatives as jnk-inhibitors |
| EP1193256A1 (en) | 2000-09-27 | 2002-04-03 | Applied Research Systems ARS Holding N.V. | Pharmaceutically active benzsulfonamide derivatives as inhibitors of JNK proteins |
| US7129242B2 (en) | 2000-12-06 | 2006-10-31 | Signal Pharmaceuticals, Llc | Anilinopyrimidine derivatives as JNK pathway inhibitors and compositions and methods related thereto |
| CA2437248A1 (en) | 2001-02-02 | 2002-08-15 | Takeda Chemical Industries, Ltd. | Jnk inhibitor |
| GB0108770D0 (en) | 2001-04-06 | 2001-05-30 | Eisai London Res Lab Ltd | Inhibitors |
| CN1300116C (zh) | 2001-04-16 | 2007-02-14 | 卫材株式会社 | 1h－吲唑化合物 |
| WO2003018020A1 (en) | 2001-08-23 | 2003-03-06 | Takeda Chemical Industries, Ltd. | Jnk inhibitors |
| WO2003024967A2 (en) | 2001-09-19 | 2003-03-27 | Aventis Pharma S.A. | Indolizines as kinase protein inhibitors |
| JP2003129190A (ja) | 2001-10-19 | 2003-05-08 | Sumitomo Metal Ind Ltd | マルテンサイト系ステンレス鋼およびその製造方法 |
| US20030138819A1 (en) | 2001-10-26 | 2003-07-24 | Haiqing Gong | Method for detecting disease |
| ATE465153T1 (de) * | 2002-02-28 | 2010-05-15 | Eisai R&D Man Co Ltd | Neue indazolverbindungen mit kondensiertem ring |
| KR20040104566A (ko) * | 2002-04-30 | 2004-12-10 | 알콘, 인코퍼레이티드 | 안압 저하 및 녹내장성 망막병증/시신경병증 치료를 위한특유의 수단으로서의 결합 조직 성장 인자 (ｃｔｇｆ)의활성 및/또는 발현 조절, 저해, 또는 변조제 |
| US7465736B2 (en) | 2002-06-14 | 2008-12-16 | Laboratoires Serono S.A. | Azole methylidene cyanide derivatives and their use as protein kinase modulators |
| CA2497977A1 (en) * | 2002-09-20 | 2004-04-01 | Alcon, Inc. | Use of cytokine synthesis inhibitors for the treatment of dry eye disorders |
| US20040092568A1 (en) * | 2002-10-31 | 2004-05-13 | Zeldis Jerome B. | Methods for the treatment, prevention and management of macular degeneration |
| US20060094753A1 (en) * | 2004-10-29 | 2006-05-04 | Alcon, Inc. | Use of inhibitors of Jun N-terminal kinases for the treatment of glaucomatous retinopathy and ocular diseases |
| US7803824B2 (en) * | 2004-10-29 | 2010-09-28 | Alcon, Inc. | Use of inhibitors of Jun N-terminal kinases to treat glaucoma |
| US20060275797A1 (en) * | 2005-03-21 | 2006-12-07 | Alcon Manufacturing, Ltd. | Use of agents which inhibit connective tissue growth factor (CTGF) binding and signaling via the TrkA/p75NTR receptor complex for the prevention and treatment of CTGF-mediated ocular disorders |
-
2006
- 2006-03-31 US US11/394,893 patent/US7803824B2/en not_active Expired - Fee Related
-
2007
- 2007-03-14 EP EP07758510A patent/EP2004158A2/en not_active Withdrawn
- 2007-03-14 BR BRPI0710099-0A patent/BRPI0710099A2/pt not_active IP Right Cessation
- 2007-03-14 MX MX2008011319A patent/MX2008011319A/es active IP Right Grant
- 2007-03-14 KR KR1020087023895A patent/KR20080108503A/ko not_active Ceased
- 2007-03-14 JP JP2009503137A patent/JP5241033B2/ja not_active Expired - Fee Related
- 2007-03-14 CN CN2007800116928A patent/CN101415407B/zh not_active Expired - Fee Related
- 2007-03-14 ZA ZA200807667A patent/ZA200807667B/xx unknown
- 2007-03-14 AU AU2007235111A patent/AU2007235111B2/en not_active Ceased
- 2007-03-14 WO PCT/US2007/063961 patent/WO2007117849A2/en not_active Ceased
- 2007-03-14 CA CA002644721A patent/CA2644721A1/en not_active Abandoned
- 2007-03-19 TW TW096109322A patent/TWI419694B/zh not_active IP Right Cessation
- 2007-03-29 AR ARP070101334A patent/AR060222A1/es not_active Application Discontinuation
-
2010
- 2010-08-18 US US12/858,739 patent/US20100311716A1/en not_active Abandoned
-
2011
- 2011-09-14 US US13/232,410 patent/US20120004274A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20120004274A1 (en) | 2012-01-05 |
| US20100311716A1 (en) | 2010-12-09 |
| TWI419694B (zh) | 2013-12-21 |
| ZA200807667B (en) | 2010-07-28 |
| EP2004158A2 (en) | 2008-12-24 |
| WO2007117849A2 (en) | 2007-10-18 |
| TW200744601A (en) | 2007-12-16 |
| KR20080108503A (ko) | 2008-12-15 |
| AR060222A1 (es) | 2008-06-04 |
| AU2007235111A1 (en) | 2007-10-18 |
| JP2009532373A (ja) | 2009-09-10 |
| AU2007235111B2 (en) | 2012-03-22 |
| US20060172991A1 (en) | 2006-08-03 |
| CN101415407A (zh) | 2009-04-22 |
| JP5241033B2 (ja) | 2013-07-17 |
| CA2644721A1 (en) | 2007-10-18 |
| CN101415407B (zh) | 2011-05-11 |
| US7803824B2 (en) | 2010-09-28 |
| MX2008011319A (es) | 2008-09-19 |
| WO2007117849A3 (en) | 2008-04-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20100280089A1 (en) | Use of inhibitors of jun n-terminal kinases for the treatment of glaucomatous retinopathy and ocular diseases | |
| BRPI0710099A2 (pt) | uso de inibidores de quìnases jun n-terminais para tratar glaucoma | |
| CA2353527C (en) | Use of neurotrophic factor stimulators for the treatment of ophthalmic neurodegenerative diseases | |
| JP2009227671A (ja) | 視神経障害を伴う眼疾患の予防又は治療剤 | |
| US6906077B1 (en) | Use of neurotrophic factor stimulators for the treatment of ophthalmic neurodegenerative diseases | |
| AU2011205120A1 (en) | Use of inhibitors of Jun N-terminal kinases for the treatment of glaucomatous retinopathy and ocular diseases | |
| MXPA01002895A (en) | Use of neurotrophic factor stimulators for the treatment of ophthalmic neurodegenerative diseases | |
| KR20070019001A (ko) | 안구 신경퇴행성 질환의 치료를 위한 신경성 인자 자극제 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B08F | Application dismissed because of non-payment of annual fees [chapter 8.6 patent gazette] |
Free format text: REFERENTE A 9A ANUIDADE. |
|
| B08K | Patent lapsed as no evidence of payment of the annual fee has been furnished to inpi [chapter 8.11 patent gazette] |
Free format text: EM VIRTUDE DO ARQUIVAMENTO PUBLICADO NA RPI 2368 DE 24-05-2016 E CONSIDERANDO AUSENCIA DE MANIFESTACAO DENTRO DOS PRAZOS LEGAIS, INFORMO QUE CABE SER MANTIDO O ARQUIVAMENTO DO PEDIDO DE PATENTE, CONFORME O DISPOSTO NO ARTIGO 12, DA RESOLUCAO 113/2013. |