CA2706203A1 - Use of mnk inhibitors for the treatment of alzheimer's disease - Google Patents
Use of mnk inhibitors for the treatment of alzheimer's disease Download PDFInfo
- Publication number
- CA2706203A1 CA2706203A1 CA2706203A CA2706203A CA2706203A1 CA 2706203 A1 CA2706203 A1 CA 2706203A1 CA 2706203 A CA2706203 A CA 2706203A CA 2706203 A CA2706203 A CA 2706203A CA 2706203 A1 CA2706203 A1 CA 2706203A1
- Authority
- CA
- Canada
- Prior art keywords
- mnk1
- disease
- mnk2
- kinase
- tau
- 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
- 238000011282 treatment Methods 0.000 title claims abstract description 25
- 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 23
- 239000003112 inhibitor Substances 0.000 title claims description 17
- 101710138999 MAP kinase-interacting serine/threonine-protein kinase 2 Proteins 0.000 claims abstract description 67
- 102100033610 MAP kinase-interacting serine/threonine-protein kinase 2 Human genes 0.000 claims abstract description 66
- 101710139011 MAP kinase-interacting serine/threonine-protein kinase 1 Proteins 0.000 claims abstract description 50
- 102100026299 MAP kinase-interacting serine/threonine-protein kinase 1 Human genes 0.000 claims abstract description 50
- 230000000694 effects Effects 0.000 claims abstract description 30
- 208000034799 Tauopathies Diseases 0.000 claims abstract description 22
- 230000002265 prevention Effects 0.000 claims abstract description 20
- 238000003745 diagnosis Methods 0.000 claims abstract description 17
- 102000013498 tau Proteins Human genes 0.000 claims description 52
- 108010026424 tau Proteins Proteins 0.000 claims description 52
- 230000026731 phosphorylation Effects 0.000 claims description 37
- 238000006366 phosphorylation reaction Methods 0.000 claims description 37
- 150000001875 compounds Chemical class 0.000 claims description 35
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 19
- 101000891579 Homo sapiens Microtubule-associated protein tau Proteins 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 16
- 102000057063 human MAPT Human genes 0.000 claims description 16
- 239000003795 chemical substances by application Substances 0.000 claims description 15
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 11
- 238000012216 screening Methods 0.000 claims description 11
- 210000004027 cell Anatomy 0.000 claims description 10
- 210000002682 neurofibrillary tangle Anatomy 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 210000004556 brain Anatomy 0.000 claims description 6
- -1 pyrrolopyrimidine compound Chemical class 0.000 claims description 6
- OGEBRHQLRGFBNV-RZDIXWSQSA-N chembl2036808 Chemical compound C12=NC(NCCCC)=NC=C2C(C=2C=CC(F)=CC=2)=NN1C[C@H]1CC[C@H](N)CC1 OGEBRHQLRGFBNV-RZDIXWSQSA-N 0.000 claims description 5
- 230000000750 progressive effect Effects 0.000 claims description 5
- RBNBDIMXFJYDLQ-UHFFFAOYSA-N thieno[3,2-d]pyrimidine Chemical group C1=NC=C2SC=CC2=N1 RBNBDIMXFJYDLQ-UHFFFAOYSA-N 0.000 claims description 5
- 206010012289 Dementia Diseases 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 4
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical group O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000008177 pharmaceutical agent Substances 0.000 claims description 4
- 102000053642 Catalytic RNA Human genes 0.000 claims description 3
- 108090000994 Catalytic RNA Proteins 0.000 claims description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 3
- 208000027089 Parkinsonian disease Diseases 0.000 claims description 3
- 206010034010 Parkinsonism Diseases 0.000 claims description 3
- 230000000692 anti-sense effect Effects 0.000 claims description 3
- 239000000544 cholinesterase inhibitor Substances 0.000 claims description 3
- 210000000349 chromosome Anatomy 0.000 claims description 3
- 230000003834 intracellular effect Effects 0.000 claims description 3
- 108091092562 ribozyme Proteins 0.000 claims description 3
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 2
- 208000011990 Corticobasal Degeneration Diseases 0.000 claims description 2
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 claims description 2
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 claims description 2
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 2
- 208000009093 Diffuse Neurofibrillary Tangles with Calcification Diseases 0.000 claims description 2
- 201000010374 Down Syndrome Diseases 0.000 claims description 2
- 206010018341 Gliosis Diseases 0.000 claims description 2
- 208000001089 Multiple system atrophy Diseases 0.000 claims description 2
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 2
- 102000029797 Prion Human genes 0.000 claims description 2
- 108091000054 Prion Proteins 0.000 claims description 2
- 108091030071 RNAI Proteins 0.000 claims description 2
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 claims description 2
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 claims description 2
- 206010044688 Trisomy 21 Diseases 0.000 claims description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
- 238000002648 combination therapy Methods 0.000 claims description 2
- 208000017004 dementia pugilistica Diseases 0.000 claims description 2
- 229960003530 donepezil Drugs 0.000 claims description 2
- 229960003980 galantamine Drugs 0.000 claims description 2
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 claims description 2
- 230000009368 gene silencing by RNA Effects 0.000 claims description 2
- 230000007387 gliosis Effects 0.000 claims description 2
- 201000008319 inclusion body myositis Diseases 0.000 claims description 2
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical group C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 claims description 2
- 229960004640 memantine Drugs 0.000 claims description 2
- 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 2
- 238000009097 single-agent therapy Methods 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 claims 2
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 claims 2
- 208000014060 Niemann-Pick disease Diseases 0.000 claims 1
- 239000000032 diagnostic agent Substances 0.000 claims 1
- 229940039227 diagnostic agent Drugs 0.000 claims 1
- 108091000080 Phosphotransferase Proteins 0.000 abstract description 24
- 102000020233 phosphotransferase Human genes 0.000 abstract description 24
- 125000000217 alkyl group Chemical group 0.000 description 32
- 229910052757 nitrogen Inorganic materials 0.000 description 32
- 229910052717 sulfur Inorganic materials 0.000 description 31
- 125000005842 heteroatom Chemical group 0.000 description 30
- 125000000623 heterocyclic group Chemical group 0.000 description 15
- 229910052739 hydrogen Inorganic materials 0.000 description 14
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 13
- 229910052736 halogen Inorganic materials 0.000 description 13
- 230000004770 neurodegeneration Effects 0.000 description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 12
- 239000001257 hydrogen Substances 0.000 description 11
- 102000029749 Microtubule Human genes 0.000 description 10
- 108091022875 Microtubule Proteins 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 125000001072 heteroaryl group Chemical group 0.000 description 10
- 150000002431 hydrogen Chemical group 0.000 description 10
- 230000001965 increasing effect Effects 0.000 description 10
- 210000004688 microtubule Anatomy 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 125000006584 (C3-C10) heterocycloalkyl group Chemical group 0.000 description 9
- 125000003118 aryl group Chemical group 0.000 description 9
- 230000027455 binding Effects 0.000 description 9
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 8
- 125000000753 cycloalkyl group Chemical group 0.000 description 8
- 125000005843 halogen group Chemical group 0.000 description 8
- 208000015122 neurodegenerative disease Diseases 0.000 description 8
- 102000005233 Eukaryotic Initiation Factor-4E Human genes 0.000 description 7
- 108060002636 Eukaryotic Initiation Factor-4E Proteins 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 150000007523 nucleic acids Chemical group 0.000 description 7
- 101150024075 Mapk1 gene Proteins 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 102000039446 nucleic acids Human genes 0.000 description 6
- 108020004707 nucleic acids Proteins 0.000 description 6
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 4
- 102000001253 Protein Kinase Human genes 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 108060006633 protein kinase Proteins 0.000 description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical group NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 239000004202 carbamide Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000001537 neural effect Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 description 2
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101000573522 Homo sapiens MAP kinase-interacting serine/threonine-protein kinase 1 Proteins 0.000 description 2
- 101001018978 Homo sapiens MAP kinase-interacting serine/threonine-protein kinase 2 Proteins 0.000 description 2
- 108091054455 MAP kinase family Proteins 0.000 description 2
- 102000043136 MAP kinase family Human genes 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000006583 body weight regulation Effects 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000006951 hyperphosphorylation Effects 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 239000011535 reaction buffer Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 230000035924 thermogenesis Effects 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 125000006720 (C1-C6) alkyl (C6-C10) aryl group Chemical group 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- BZPHUKZURKMUCF-UHFFFAOYSA-N 3-ethoxy-4-[(5-methylthieno[2,3-d]pyrimidin-4-yl)amino]benzamide Chemical compound CCOC1=CC(C(N)=O)=CC=C1NC1=NC=NC2=C1C(C)=CS2 BZPHUKZURKMUCF-UHFFFAOYSA-N 0.000 description 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 241000255601 Drosophila melanogaster Species 0.000 description 1
- 241001269524 Dura Species 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 208000030814 Eating disease Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 208000019454 Feeding and Eating disease Diseases 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 239000012741 Laemmli sample buffer Substances 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 101150018665 MAPK3 gene Proteins 0.000 description 1
- 102000044589 Mitogen-Activated Protein Kinase 1 Human genes 0.000 description 1
- 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 description 1
- 102100023482 Mitogen-activated protein kinase 14 Human genes 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
- 208000010577 Niemann-Pick disease type C Diseases 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 241000005308 Orsa Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 208000007930 Type C Niemann-Pick Disease Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000007792 alzheimer disease pathology Effects 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000003376 axonal effect Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 150000001602 bicycloalkyls Chemical group 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 201000001883 cholelithiasis Diseases 0.000 description 1
- 230000006999 cognitive decline Effects 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 235000014632 disordered eating Nutrition 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 238000012252 genetic analysis Methods 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
- 102000057747 human MKNK1 Human genes 0.000 description 1
- 102000056485 human MKNK2 Human genes 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 108091011150 microtubule binding proteins Proteins 0.000 description 1
- 102000021160 microtubule binding proteins Human genes 0.000 description 1
- 230000008880 microtubule cytoskeleton organization Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 230000014511 neuron projection development Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 150000004633 phorbol derivatives Chemical class 0.000 description 1
- 239000002644 phorbol ester Substances 0.000 description 1
- 229920001992 poloxamer 407 Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 150000004944 pyrrolopyrimidines Chemical class 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 201000002859 sleep apnea Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 230000006354 stress signaling Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 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
- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Landscapes
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Physical Education & Sports Medicine (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP07022695 | 2007-11-22 | ||
| EP07022695.6 | 2007-11-22 | ||
| PCT/EP2008/009880 WO2009065596A2 (en) | 2007-11-22 | 2008-11-21 | Use of mnk inhibitors for the treatment of alzheimer's disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2706203A1 true CA2706203A1 (en) | 2009-05-28 |
Family
ID=40404966
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2706203A Abandoned CA2706203A1 (en) | 2007-11-22 | 2008-11-21 | Use of mnk inhibitors for the treatment of alzheimer's disease |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20100247517A1 (https=) |
| EP (1) | EP2219649A2 (https=) |
| JP (1) | JP2011504474A (https=) |
| CA (1) | CA2706203A1 (https=) |
| WO (1) | WO2009065596A2 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102858782A (zh) * | 2010-02-26 | 2013-01-02 | 贝林格尔.英格海姆国际有限公司 | 用于药物组合物的具有Mnk1/Mnk2 抑制活性的4-[环烷基氧基(杂)芳基氨基]噻吩并[2,3-d]嘧啶 |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1899353A1 (en) * | 2005-06-22 | 2008-03-19 | DeveloGen Aktiengesellschaft | Thienopyrimidines for pharmaceutical compositions |
| CA2651898A1 (en) | 2006-04-07 | 2007-10-18 | Develogen Aktiengesellschaft | Thienopyrimidines having mnk1/mnk2 inhibiting activity for pharmaceutical compositions |
| EP1889847A1 (en) * | 2006-07-10 | 2008-02-20 | DeveloGen Aktiengesellschaft | Pyrrolopyrimidines for pharmaceutical compositions |
| WO2008149147A2 (en) * | 2007-06-06 | 2008-12-11 | Domantis Limited | Polypeptides, antibody variable domains and antagonists |
| MX2011001938A (es) | 2008-08-26 | 2011-03-29 | Boehringer Ingelheim Int | Tienopirimidinas para composiciones farmaceuticas. |
| EP2539343B1 (en) * | 2010-02-26 | 2015-12-30 | Evotec International GmbH | Thienopyrimidines containing a substituted alkyl group for pharmaceutical compositions |
| UY33241A (es) * | 2010-02-26 | 2011-09-30 | Boehringer Ingelheim Int | ?Tienopirimidinas que contienen heterocicloalquilo para composiciones farmacéuticas?. |
| EP2734517B1 (en) * | 2011-07-18 | 2017-08-30 | Merck Patent GmbH | Benzamides |
| EP3134405B1 (en) | 2014-04-25 | 2019-08-28 | Pfizer Inc | Heteroaromatic compounds and their use as dopamine d1 ligands |
| GB201520499D0 (en) * | 2015-11-20 | 2016-01-06 | Medical Res Council Technology | Compounds |
| GB201520500D0 (en) * | 2015-11-20 | 2016-01-06 | Medical Res Council Technology | Compounds |
| BR112019016707A2 (pt) | 2017-02-14 | 2020-04-07 | Effector Therapeutics Inc | inibidores de mnk substituídos por piperidina e métodos relacionados aos mesmos |
| TWI857981B (zh) | 2018-10-24 | 2024-10-11 | 美商伊凡克特治療公司 | Ｍｎｋ抑制劑的結晶形式 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW370529B (en) * | 1992-12-17 | 1999-09-21 | Pfizer | Pyrazolopyrimidines |
| EP0729758A3 (en) * | 1995-03-02 | 1997-10-29 | Pfizer | Pyrazolopyrimidines and pyrrolopyrimidines for the treatment of neuronal and other diseases |
| GB9906566D0 (en) * | 1999-03-23 | 1999-05-19 | Zeneca Ltd | Chemical compounds |
| US7419978B2 (en) * | 2003-10-22 | 2008-09-02 | Bristol-Myers Squibb Company | Phenyl-aniline substituted bicyclic compounds useful as kinase inhibitors |
| ATE486592T1 (de) * | 2004-01-05 | 2010-11-15 | Merz Pharma Gmbh & Co Kgaa | Memantin für die behandlung von leichtem bis mittelschwerem morbus alzheimer |
| GB0412467D0 (en) * | 2004-06-04 | 2004-07-07 | Astrazeneca Ab | Chemical compounds |
| EP1746099A1 (en) * | 2004-12-23 | 2007-01-24 | DeveloGen Aktiengesellschaft | Mnk1 or Mnk2 inhibitors |
| EP1899353A1 (en) * | 2005-06-22 | 2008-03-19 | DeveloGen Aktiengesellschaft | Thienopyrimidines for pharmaceutical compositions |
| WO2007059905A2 (en) * | 2005-11-25 | 2007-05-31 | Develogen Aktiengesellschaft | Thienopyrimidines treating inflammatory diseases |
| ES2394348T3 (es) * | 2006-03-29 | 2013-01-30 | Velacor Therapeutics Pty Ltd | Tratamiento de enfermedades neurodegenerativas con selenato |
| FR2899107B1 (fr) * | 2006-03-30 | 2008-06-13 | Neurokin Entpr Unipersonnelle | Utilisation de la (s)-roscovitine pour la fabrication d'un medicament |
| CA2651898A1 (en) * | 2006-04-07 | 2007-10-18 | Develogen Aktiengesellschaft | Thienopyrimidines having mnk1/mnk2 inhibiting activity for pharmaceutical compositions |
| EP2012806A4 (en) * | 2006-04-24 | 2010-07-28 | Alltech Inc | METHOD AND COMPOSITIONS FOR MODIFYING CELL FUNCTIONS |
| CA2654358A1 (en) * | 2006-06-22 | 2007-12-27 | Biovitrum Ab (Publ) | Pyridine and pyrazine derivatives as mnk kinase inhibitors |
-
2008
- 2008-11-21 EP EP08852675A patent/EP2219649A2/en not_active Withdrawn
- 2008-11-21 JP JP2010534409A patent/JP2011504474A/ja active Pending
- 2008-11-21 WO PCT/EP2008/009880 patent/WO2009065596A2/en not_active Ceased
- 2008-11-21 US US12/744,374 patent/US20100247517A1/en not_active Abandoned
- 2008-11-21 CA CA2706203A patent/CA2706203A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102858782A (zh) * | 2010-02-26 | 2013-01-02 | 贝林格尔.英格海姆国际有限公司 | 用于药物组合物的具有Mnk1/Mnk2 抑制活性的4-[环烷基氧基(杂)芳基氨基]噻吩并[2,3-d]嘧啶 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2219649A2 (en) | 2010-08-25 |
| WO2009065596A3 (en) | 2009-08-20 |
| WO2009065596A2 (en) | 2009-05-28 |
| JP2011504474A (ja) | 2011-02-10 |
| US20100247517A1 (en) | 2010-09-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2706203A1 (en) | Use of mnk inhibitors for the treatment of alzheimer's disease | |
| Summer et al. | Activation of the mTORC1/PGC-1 axis promotes mitochondrial biogenesis and induces cellular senescence in the lung epithelium | |
| KR101611824B1 (ko) | 세포 스트레스 반응 조절을 통한 알츠하이머 질환 및 관련 장애의 치료를 위한 신규 치료학적 접근법 | |
| Halliday et al. | Fine‐tuning PERK signaling for neuroprotection | |
| TWI791507B (zh) | 使用ccr3-抑制劑治療老化相關損傷之方法及組合物 | |
| US20050075351A1 (en) | Use | |
| JP2020521734A (ja) | 老化細胞除去化合物 | |
| CN111788186A (zh) | 治疗包括痴呆的神经紊乱的组合物和方法 | |
| WO2013026021A2 (en) | Trka as a target for inhibiting app cleavage and/or progression of alzheimer's disease | |
| EP3193869A1 (en) | Perk activator for the treatment of neurodegenerative diseases | |
| AU2017383127B2 (en) | Caspase-1 inhibition and uses thereof for prevention and treatment of neurological conditions | |
| US20100240647A1 (en) | Treatment of Alzheimer's Disease and Related Conditions | |
| JP2025142087A (ja) | アルファ－シヌクレインの調節因子 | |
| Karati et al. | Unlocking the Therapeutic Potential of the Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A Inhibitors in Alzheimer’s Diseases | |
| US12274703B2 (en) | Compositions and methods of treatment for neurological disorders comprising a dementia | |
| JP2024517653A (ja) | 神経細胞プロテオームを崩壊に対して安定化して血管細胞を保護する方法 | |
| US9289448B2 (en) | Compositions and methods for treating alzheimer's disease and other tauopathies | |
| US20080051403A1 (en) | Treatment For Alzheimer's Disease And Related Conditions | |
| CN104039324B (zh) | 减少β淀粉样蛋白负载的组合物和方法 | |
| CA3111433C (en) | Methods and compositions for treating aging-associated impairments using ccr3-inhibitors | |
| WO2011039394A2 (es) | Utilización de la gimnodimina, análogos y derivados para el tratamiento y/o la prevención de enfermedades neurodegenerativas relacionadas con tau y b-amiloide | |
| WO2017086385A1 (ja) | Ｐａｒ１阻害をメカニズムとする異所性骨化の治療薬剤 | |
| EA041892B1 (ru) | Способы и композиции для лечения ассоциированных со старением нарушений с применением ccr3-ингибиторов | |
| WO2015199503A1 (ko) | Cx-4945를 유효성분으로 함유하는 퇴행성 뇌질환 예방 및 치료용 약학적 조성물 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |
Effective date: 20131121 |