JP2013525330A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2013525330A5 JP2013525330A5 JP2013505466A JP2013505466A JP2013525330A5 JP 2013525330 A5 JP2013525330 A5 JP 2013525330A5 JP 2013505466 A JP2013505466 A JP 2013505466A JP 2013505466 A JP2013505466 A JP 2013505466A JP 2013525330 A5 JP2013525330 A5 JP 2013525330A5
- Authority
- JP
- Japan
- Prior art keywords
- group
- conjugate
- reuptake inhibitor
- serotonin
- norepinephrine
- 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.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 claims description 39
- 239000003795 chemical substances by application Substances 0.000 claims description 35
- 239000000221 dopamine uptake inhibitor Substances 0.000 claims description 33
- 108020004999 messenger RNA Proteins 0.000 claims description 25
- 108091034117 Oligonucleotide Proteins 0.000 claims description 24
- 229940094659 Dopamine reuptake inhibitor Drugs 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 239000001257 hydrogen Substances 0.000 claims description 21
- 229940111055 Serotonin-norepinephrine-dopamine reuptake inhibitor Drugs 0.000 claims description 18
- 239000003174 triple reuptake inhibitor Substances 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 claims description 15
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 14
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 claims description 14
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 102000005665 Neurotransmitter Transport Proteins Human genes 0.000 claims description 10
- 108010084810 Neurotransmitter Transport Proteins Proteins 0.000 claims description 10
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 10
- 238000011282 treatment Methods 0.000 claims description 10
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 claims description 9
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 102000019208 Serotonin Plasma Membrane Transport Proteins Human genes 0.000 claims description 8
- 108010012996 Serotonin Plasma Membrane Transport Proteins Proteins 0.000 claims description 8
- 210000004027 cell Anatomy 0.000 claims description 8
- 125000001188 haloalkyl group Chemical group 0.000 claims description 8
- 150000007523 nucleic acids Chemical class 0.000 claims description 8
- 102000003802 alpha-Synuclein Human genes 0.000 claims description 7
- 108090000185 alpha-Synuclein Proteins 0.000 claims description 7
- 239000002767 noradrenalin uptake inhibitor Substances 0.000 claims description 7
- 125000006239 protecting group Chemical group 0.000 claims description 7
- 108010015720 Dopamine beta-Hydroxylase Proteins 0.000 claims description 6
- 102100033156 Dopamine beta-hydroxylase Human genes 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- 150000002243 furanoses Chemical class 0.000 claims description 6
- 150000002772 monosaccharides Chemical class 0.000 claims description 6
- 108020004707 nucleic acids Proteins 0.000 claims description 6
- 102000039446 nucleic acids Human genes 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 5
- 102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 claims description 5
- 101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 claims description 5
- -1 alkylene glycols Chemical class 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 229940127221 norepinephrine reuptake inhibitor Drugs 0.000 claims description 4
- 230000000295 complement effect Effects 0.000 claims description 3
- 230000008021 deposition Effects 0.000 claims description 3
- 210000004558 lewy body Anatomy 0.000 claims description 3
- 229920001184 polypeptide Polymers 0.000 claims description 3
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 3
- 102000040650 (ribonucleotides)n+m Human genes 0.000 claims description 2
- 108091023037 Aptamer Proteins 0.000 claims description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 2
- 102000053642 Catalytic RNA Human genes 0.000 claims description 2
- 108090000994 Catalytic RNA Proteins 0.000 claims description 2
- YTBSYETUWUMLBZ-UHFFFAOYSA-N D-Erythrose Chemical class OCC(O)C(O)C=O YTBSYETUWUMLBZ-UHFFFAOYSA-N 0.000 claims description 2
- YTBSYETUWUMLBZ-IUYQGCFVSA-N D-erythrose Chemical class OC[C@@H](O)[C@@H](O)C=O YTBSYETUWUMLBZ-IUYQGCFVSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 claims description 2
- 206010056474 Erythrosis Diseases 0.000 claims description 2
- 229930091371 Fructose Natural products 0.000 claims description 2
- 239000005715 Fructose Substances 0.000 claims description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 2
- 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 claims description 2
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 claims description 2
- 108020004459 Small interfering RNA Proteins 0.000 claims description 2
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims description 2
- 150000001408 amides Chemical class 0.000 claims description 2
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 2
- 238000012230 antisense oligonucleotides Methods 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Chemical class CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 claims description 2
- 230000000694 effects Effects 0.000 claims description 2
- 229930182830 galactose Natural products 0.000 claims description 2
- 230000009368 gene silencing by RNA Effects 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-O guanidinium Chemical compound NC(N)=[NH2+] ZRALSGWEFCBTJO-UHFFFAOYSA-O 0.000 claims description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 2
- 230000005764 inhibitory process Effects 0.000 claims description 2
- 230000002452 interceptive effect Effects 0.000 claims description 2
- 125000005647 linker group Chemical group 0.000 claims description 2
- 125000003473 lipid group Chemical group 0.000 claims description 2
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 claims description 2
- 239000000178 monomer Substances 0.000 claims description 2
- 229960002748 norepinephrine Drugs 0.000 claims description 2
- 150000004713 phosphodiesters Chemical class 0.000 claims description 2
- 108091092562 ribozyme Proteins 0.000 claims description 2
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical class CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 claims description 2
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 claims description 2
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 claims description 2
- 150000003457 sulfones Chemical class 0.000 claims description 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 5
- 229940126569 noradrenaline reuptake inhibitor Drugs 0.000 claims 3
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims 2
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 claims 1
- 229930182837 (R)-adrenaline Natural products 0.000 claims 1
- 241000222336 Ganoderma Species 0.000 claims 1
- 239000000556 agonist Substances 0.000 claims 1
- 238000010276 construction Methods 0.000 claims 1
- 230000006806 disease prevention Effects 0.000 claims 1
- 229960005139 epinephrine Drugs 0.000 claims 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 229940076279 serotonin Drugs 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 description 17
- 201000010099 disease Diseases 0.000 description 13
- 238000000034 method Methods 0.000 description 11
- 239000003112 inhibitor Substances 0.000 description 8
- 229940121991 Serotonin and norepinephrine reuptake inhibitor Drugs 0.000 description 7
- 239000003775 serotonin noradrenalin reuptake inhibitor Substances 0.000 description 7
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 6
- 230000002474 noradrenergic effect Effects 0.000 description 5
- 201000011240 Frontotemporal dementia Diseases 0.000 description 4
- 102000008092 Norepinephrine Plasma Membrane Transport Proteins Human genes 0.000 description 4
- 108010049586 Norepinephrine Plasma Membrane Transport Proteins Proteins 0.000 description 4
- 229960003638 dopamine Drugs 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 229940126570 serotonin reuptake inhibitor Drugs 0.000 description 4
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 4
- 229960002073 sertraline Drugs 0.000 description 4
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 4
- 0 Cc1cc(C(C(*)(*)C2(*)**(*N*)C3=O)c4ccccc4C2N3I)ccc1 Chemical compound Cc1cc(C(C(*)(*)C2(*)**(*N*)C3=O)c4ccccc4C2N3I)ccc1 0.000 description 3
- 208000023105 Huntington disease Diseases 0.000 description 3
- 208000018737 Parkinson disease Diseases 0.000 description 3
- 206010034010 Parkinsonism Diseases 0.000 description 3
- 125000006242 amine protecting group Chemical group 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 201000002832 Lewy body dementia Diseases 0.000 description 2
- 208000001089 Multiple system atrophy Diseases 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 2
- 208000012202 Pervasive developmental disease Diseases 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 208000029560 autism spectrum disease Diseases 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 239000002843 gaba uptake inhibitor Substances 0.000 description 2
- 239000012216 imaging agent Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 230000016273 neuron death Effects 0.000 description 2
- 230000009223 neuronal apoptosis Effects 0.000 description 2
- 239000002405 nuclear magnetic resonance imaging agent Substances 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 208000028173 post-traumatic stress disease Diseases 0.000 description 2
- 230000000862 serotonergic effect Effects 0.000 description 2
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 1
- WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 description 1
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
- 101150016096 17 gene Proteins 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 102000034263 Amino acid transporters Human genes 0.000 description 1
- 108050005273 Amino acid transporters Proteins 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- YVVVQVSPNGMJAX-QCDSWUKFSA-N CN([C@@H](CC1)c2ccccc2[C@@H]1c(cc1)cc(Cl)c1Cl)C(CCCCCNC(CCC(NCCCCCCOP(O)(O)=O)=O)=O)=O Chemical compound CN([C@@H](CC1)c2ccccc2[C@@H]1c(cc1)cc(Cl)c1Cl)C(CCCCCNC(CCC(NCCCCCCOP(O)(O)=O)=O)=O)=O YVVVQVSPNGMJAX-QCDSWUKFSA-N 0.000 description 1
- 208000010693 Charcot-Marie-Tooth Disease Diseases 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 206010067889 Dementia with Lewy bodies Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- 208000030814 Eating disease Diseases 0.000 description 1
- 208000019454 Feeding and Eating disease Diseases 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 206010068871 Myotonic dystrophy Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 206010033892 Paraplegia Diseases 0.000 description 1
- 208000027089 Parkinsonian disease Diseases 0.000 description 1
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 1
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
- 208000024777 Prion disease Diseases 0.000 description 1
- 208000032930 Spastic paraplegia Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 102000019355 Synuclein Human genes 0.000 description 1
- 108050006783 Synuclein Proteins 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 229930003827 cannabinoid Natural products 0.000 description 1
- 239000003557 cannabinoid Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 229960001653 citalopram Drugs 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- USRHYDPUVLEVMC-FQEVSTJZSA-N dapoxetine Chemical compound C1([C@H](CCOC=2C3=CC=CC=C3C=CC=2)N(C)C)=CC=CC=C1 USRHYDPUVLEVMC-FQEVSTJZSA-N 0.000 description 1
- 229960005217 dapoxetine Drugs 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 208000017004 dementia pugilistica Diseases 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 235000014632 disordered eating Nutrition 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229960004341 escitalopram Drugs 0.000 description 1
- WSEQXVZVJXJVFP-FQEVSTJZSA-N escitalopram Chemical compound C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-FQEVSTJZSA-N 0.000 description 1
- 230000002461 excitatory amino acid Effects 0.000 description 1
- 239000003257 excitatory amino acid Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 229960002464 fluoxetine Drugs 0.000 description 1
- 229960004038 fluvoxamine Drugs 0.000 description 1
- CJOFXWAVKWHTFT-XSFVSMFZSA-N fluvoxamine Chemical compound COCCCC\C(=N/OCCN)C1=CC=C(C(F)(F)F)C=C1 CJOFXWAVKWHTFT-XSFVSMFZSA-N 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical group [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 230000005891 glutamate uptake involved in synaptic transmission Effects 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000003384 imaging method Methods 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
- 238000007914 intraventricular administration Methods 0.000 description 1
- 201000010901 lateral sclerosis Diseases 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 208000024714 major depressive disease Diseases 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 230000020763 muscle atrophy Effects 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 208000021090 palsy Diseases 0.000 description 1
- 229960002296 paroxetine Drugs 0.000 description 1
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 1
- 210000000211 third ventricle Anatomy 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US32551510P | 2010-04-19 | 2010-04-19 | |
| EP10382087.4 | 2010-04-19 | ||
| EP10382087A EP2380595A1 (en) | 2010-04-19 | 2010-04-19 | Compositions and methods for selective delivery of oligonucleotide molecules to specific neuron types |
| US61/325,515 | 2010-04-19 | ||
| EP11382031.0 | 2011-02-09 | ||
| EP11382031 | 2011-02-09 | ||
| PCT/EP2011/056270 WO2011131693A2 (en) | 2010-04-19 | 2011-04-19 | Compositions and methods for selective delivery of oligonucleotide molecules to specific neuron types |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2013525330A JP2013525330A (ja) | 2013-06-20 |
| JP2013525330A5 true JP2013525330A5 (enExample) | 2014-06-19 |
| JP5819401B2 JP5819401B2 (ja) | 2015-11-24 |
Family
ID=44063382
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013505466A Active JP5819401B2 (ja) | 2010-04-19 | 2011-04-19 | 組成物及びオリゴヌクレオチド分子を特異的なニューロンのタイプに選択的に送達する方法 |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US9193969B2 (enExample) |
| EP (2) | EP3231446A1 (enExample) |
| JP (1) | JP5819401B2 (enExample) |
| KR (1) | KR20130103662A (enExample) |
| AR (1) | AR083715A1 (enExample) |
| AU (4) | AU2011244321A1 (enExample) |
| BR (1) | BR112012026471A2 (enExample) |
| CA (1) | CA2796722C (enExample) |
| DK (1) | DK2560687T3 (enExample) |
| ES (1) | ES2638309T3 (enExample) |
| LT (1) | LT2560687T (enExample) |
| MX (1) | MX342764B (enExample) |
| RU (1) | RU2664452C2 (enExample) |
| WO (1) | WO2011131693A2 (enExample) |
Families Citing this family (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1463512B1 (en) | 2002-01-11 | 2014-05-28 | biOasis Technologies Inc. | Use of p97 as an enzyme delivery system for the delivery of therapeutic lysosomal enzymes |
| DK2560687T3 (en) | 2010-04-19 | 2017-09-18 | Nlife Therapeutics S L | Preparations and Methods for Selective Delivery of Oligonucleotide Molecules to Specific Neuron Types |
| CA2817960C (en) | 2010-11-17 | 2020-06-09 | Isis Pharmaceuticals, Inc. | Modulation of alpha synuclein expression |
| PT2717917T (pt) | 2011-07-05 | 2016-07-27 | Bioasis Technologies Inc | Conjugados de anticorpos p97 |
| ES2632212T3 (es) | 2011-08-04 | 2017-09-11 | Yeda Research And Development Co. Ltd. | miR-135 y composiciones que lo comprenden para el tratamiento de afecciones médicas asociadas con la serotonina |
| CA2858576A1 (en) * | 2011-12-06 | 2013-06-13 | Research Institute At Nationwide Children's Hospital | Non-ionic, low osmolar contrast agents for delivery of antisense oligonucleotides and treatment of disease |
| WO2013148260A1 (en) | 2012-03-30 | 2013-10-03 | Washington University | Methods for modulating tau expression for reducing seizure and modifying a neurodegenerative syndrome |
| AU2013296557B2 (en) | 2012-07-31 | 2019-04-18 | Bioasis Technologies Inc. | Dephosphorylated lysosomal storage disease proteins and methods of use thereof |
| AU2013336582A1 (en) * | 2012-10-26 | 2015-06-11 | Nlife Therapeutics, S.L. | Compositions and methods for selective delivery of oligonucleotide molecules to cell types |
| CA2890112A1 (en) | 2012-10-26 | 2014-05-01 | Nlife Therapeutics, S.L. | Compositions and methods for the treatment of parkinson disease by the selective delivery of oligonucleotide molecules to specific neuron types |
| EP3406718A1 (en) | 2012-11-15 | 2018-11-28 | Roche Innovation Center Copenhagen A/S | Oligonucleotide conjugates |
| EP2743695A1 (en) | 2012-12-12 | 2014-06-18 | Nanogap Sub NM Powder, S.A. | Methods and reagents for the detection of biomolecules using luminescence |
| CN105263958B (zh) | 2013-03-13 | 2019-09-27 | 比奥阿赛斯技术有限公司 | p97片段及其应用 |
| EP3766974A1 (en) | 2013-03-14 | 2021-01-20 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating tau expression |
| JP6262848B2 (ja) * | 2013-05-21 | 2018-01-17 | 成都先導薬物開発有限公司 | 薬物標的の捕獲方法 |
| CN104178515B (zh) * | 2013-05-21 | 2018-08-31 | 成都先导药物开发有限公司 | 一种化合物的细胞透膜的方法 |
| CN104177465B (zh) * | 2013-05-21 | 2017-09-29 | 成都先导药物开发有限公司 | 一种化合物给药前体及药物载体制剂 |
| TW202246503A (zh) | 2013-07-19 | 2022-12-01 | 美商百健Ｍａ公司 | 用於調節τ蛋白表現之組合物 |
| BR112016017933A2 (pt) | 2014-02-03 | 2017-10-10 | Bioasis Technologies Inc | ?proteínas de fusão p97? |
| CA2936158C (en) | 2014-02-05 | 2023-06-13 | Yeda Research And Development Co. Ltd. | Use of mir-135 or precursor thereof for the treatment and diagnosis of a bipolar disease |
| WO2015126729A1 (en) | 2014-02-19 | 2015-08-27 | Bioasis Technologies, Inc. | P97-ids fusion proteins |
| CA2943890A1 (en) * | 2014-05-01 | 2015-11-05 | Bioasis Technologies, Inc. | P97-polynucleotide conjugates |
| GB201410693D0 (en) | 2014-06-16 | 2014-07-30 | Univ Southampton | Splicing modulation |
| JP6867945B2 (ja) | 2014-10-03 | 2021-05-12 | コールド スプリング ハーバー ラボラトリー | 核内遺伝子出力の標的とされた増強 |
| MA43072A (fr) | 2015-07-22 | 2018-05-30 | Wave Life Sciences Ltd | Compositions d'oligonucléotides et procédés associés |
| US10733023B1 (en) * | 2015-08-06 | 2020-08-04 | D2Iq, Inc. | Oversubscription scheduling |
| DK3133166T4 (da) * | 2015-08-21 | 2023-03-20 | 42 Life Sciences Gmbh & Co Kg | Sammensætning og fremgangsmåde til hybridisering |
| WO2017060731A1 (en) | 2015-10-09 | 2017-04-13 | University Of Southampton | Modulation of gene expression and screening for deregulated protein expression |
| US11096956B2 (en) | 2015-12-14 | 2021-08-24 | Stoke Therapeutics, Inc. | Antisense oligomers and uses thereof |
| AU2016370653A1 (en) | 2015-12-14 | 2018-06-21 | Cold Spring Harbor Laboratory | Antisense oligomers for treatment of Autosomal Dominant Mental Retardation-5 and Dravet Syndrome |
| GB2574525B (en) * | 2015-12-21 | 2020-09-02 | Sutura Therapeutics Ltd | Improved drug delivery by conjugating oligonucleotides to stitched/stapled peptides |
| GB2545898B (en) | 2015-12-21 | 2019-10-09 | Sutura Therapeutics Ltd | Improved drug delivery by conjugating oligonucleotides to stitched/stapled peptides |
| KR101916652B1 (ko) * | 2016-06-29 | 2018-11-08 | 올릭스 주식회사 | 작은 간섭 rna의 rna 간섭효과 증진용 화합물 및 이의 용도 |
| US10208098B2 (en) * | 2016-09-15 | 2019-02-19 | Council Of Scientific & Industrial Research | Recombinant protein-based method for the delivery of silencer RNA to target the brain |
| JOP20190065A1 (ar) | 2016-09-29 | 2019-03-28 | Ionis Pharmaceuticals Inc | مركبات وطرق لتقليل التعبير عن tau |
| LT3673080T (lt) | 2017-08-25 | 2023-12-27 | Stoke Therapeutics, Inc. | Priešprasminiai oligomerai, skirti būklėms ir ligoms gydyti |
| CA3076612A1 (en) | 2017-09-22 | 2019-03-28 | John Mansell | Compositions and methods for treatment of sepsis-related disorders |
| EP3461487A1 (en) * | 2017-09-29 | 2019-04-03 | Nlife Therapeutics S.L. | Compositions and methods for the delivery of mrna to hepatic cells |
| US20210268667A1 (en) | 2017-10-23 | 2021-09-02 | Stoke Therapeutics, Inc. | Antisense oligomers for treatment of non-sense mediated rna decay based conditions and diseases |
| IL302108A (en) | 2017-10-25 | 2023-06-01 | Ac Immune Sa | Preparations of phosphorylated tau peptides and uses thereof |
| TWI809004B (zh) | 2017-11-09 | 2023-07-21 | 美商Ionis製藥公司 | 用於降低snca表現之化合物及方法 |
| BR112020014011A2 (pt) | 2018-01-12 | 2020-12-08 | Bristol-Myers Squibb Company | Oligonucleotídeos antissenso dirigidos à alfa-sinucleína e usos dos mesmos |
| IL275902B2 (en) | 2018-01-12 | 2025-10-01 | Bristol Myers Squibb Co | Antisense oligonucleotides directed against alpha-synuclein and their uses |
| BR112020012921A2 (pt) | 2018-01-12 | 2020-12-08 | Roche Innovation Center Copenhagen A/S | Oligonucleotídeos antissenso de alfa-sinucleína e usos dos mesmos |
| CA3099280A1 (en) | 2018-05-04 | 2019-11-07 | Stoke Therapeutics, Inc. | Methods and compositions for treatment of cholesteryl ester storage disease |
| CN112218877B (zh) | 2018-08-27 | 2025-07-25 | 瑞泽恩制药公司 | 拉曼光谱在下游纯化中的应用 |
| ES2698565B2 (es) * | 2018-12-12 | 2019-07-16 | Univ Madrid Complutense | Procedimiento para la elaboración de nanopartículas lipídicas, y nanopartículas lipídicas con los macrófagos cerebrales como células diana |
| CA3129252A1 (en) | 2019-02-08 | 2020-08-13 | Ac Immune S.A. | Method of safe administration of phosphorylated tau peptide vaccine |
| CN114364404A (zh) | 2019-04-11 | 2022-04-15 | 东北大学 | 寡核苷酸-聚合物多手臂偶联物以及使用方法 |
| WO2020257194A1 (en) * | 2019-06-17 | 2020-12-24 | Alnylam Pharmaceuticals, Inc. | Delivery of oligonucleotides to the striatum |
| EP4150092A4 (en) | 2020-05-11 | 2024-11-06 | Stoke Therapeutics, Inc. | OPA1 ANTISENSE OLIGOMERS FOR THE TREATMENT OF DISEASES AND CONDITIONS |
| CA3204415A1 (en) * | 2021-01-18 | 2022-07-21 | Alon Chen | Modified mir-135, conjugated form thereof, and uses of same |
| WO2024069229A2 (en) | 2022-08-03 | 2024-04-04 | Sutura Therapeutics Ltd | Biologically active compounds |
| US12396981B2 (en) | 2023-03-09 | 2025-08-26 | William Shulman | Methods of using DMT |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003042162A1 (en) * | 2001-11-17 | 2003-05-22 | Neurosearch A/S | Prodrugs of antidepressants and their use for treating depressions |
| EP1336406A1 (en) * | 2002-02-14 | 2003-08-20 | Solvay Pharmaceuticals B.V. | Partial dopamine-D2 receptor agonist plus serotonin and/or noradrenaline inhibitory activity |
| EP1711632A4 (en) * | 2004-01-19 | 2009-03-11 | Technion Res & Dev Foundation | DIAGNOSTIC TEST FOR PARKINSON |
| WO2007050789A2 (en) * | 2005-10-25 | 2007-05-03 | Nëdken Corporation | Glycosyl-oligonucleotide conjugates and methods |
| GB0605337D0 (en) | 2006-03-17 | 2006-04-26 | Genomica Sau | Treatment of CNS conditions |
| WO2008033285A2 (en) * | 2006-09-15 | 2008-03-20 | The Trustees Of Culumbia University In The City Of New York | Delivery of double-stranded rna into the central nervous system |
| EP2235175A4 (en) * | 2007-12-20 | 2012-04-25 | Angiochem Inc | POLYPEPTIDE-NUCLEIC ACID CONJUGATES AND USES THEREOF |
| GB0809476D0 (en) | 2008-05-23 | 2008-07-02 | Cambridge Entpr Ltd | Treatment of neurodegenerative disorders |
| DE102009058769A1 (de) * | 2009-12-16 | 2011-06-22 | MagForce Nanotechnologies AG, 10589 | Temperaturabhängige Aktivierung von katalytischen Nukleinsäuren zur kontrollierten Wirkstofffreisetzung |
| DK2560687T3 (en) | 2010-04-19 | 2017-09-18 | Nlife Therapeutics S L | Preparations and Methods for Selective Delivery of Oligonucleotide Molecules to Specific Neuron Types |
| CA2817960C (en) * | 2010-11-17 | 2020-06-09 | Isis Pharmaceuticals, Inc. | Modulation of alpha synuclein expression |
| AU2013336582A1 (en) | 2012-10-26 | 2015-06-11 | Nlife Therapeutics, S.L. | Compositions and methods for selective delivery of oligonucleotide molecules to cell types |
| CA2890112A1 (en) | 2012-10-26 | 2014-05-01 | Nlife Therapeutics, S.L. | Compositions and methods for the treatment of parkinson disease by the selective delivery of oligonucleotide molecules to specific neuron types |
-
2011
- 2011-04-19 DK DK11718678.3T patent/DK2560687T3/en active
- 2011-04-19 WO PCT/EP2011/056270 patent/WO2011131693A2/en not_active Ceased
- 2011-04-19 EP EP17172370.3A patent/EP3231446A1/en active Pending
- 2011-04-19 LT LTEP11718678.3T patent/LT2560687T/lt unknown
- 2011-04-19 EP EP11718678.3A patent/EP2560687B1/en active Active
- 2011-04-19 ES ES11718678.3T patent/ES2638309T3/es active Active
- 2011-04-19 JP JP2013505466A patent/JP5819401B2/ja active Active
- 2011-04-19 KR KR1020127030202A patent/KR20130103662A/ko not_active Ceased
- 2011-04-19 RU RU2012149042A patent/RU2664452C2/ru active
- 2011-04-19 AU AU2011244321A patent/AU2011244321A1/en not_active Abandoned
- 2011-04-19 BR BR112012026471A patent/BR112012026471A2/pt not_active IP Right Cessation
- 2011-04-19 MX MX2012012214A patent/MX342764B/es active IP Right Grant
- 2011-04-19 CA CA2796722A patent/CA2796722C/en active Active
- 2011-04-19 US US13/066,590 patent/US9193969B2/en active Active
- 2011-04-20 AR ARP110101361A patent/AR083715A1/es not_active Application Discontinuation
-
2015
- 2015-11-23 US US14/949,490 patent/US10071163B2/en active Active
-
2017
- 2017-06-30 AU AU2017204529A patent/AU2017204529A1/en not_active Abandoned
-
2019
- 2019-06-04 AU AU2019203887A patent/AU2019203887B2/en active Active
-
2020
- 2020-04-15 AU AU2020202533A patent/AU2020202533B2/en active Active
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2013525330A5 (enExample) | ||
| RU2012149042A (ru) | Конъюгат (варианты), способ лечения заболеваний нервной системы (варианты), способ визуализации клетки, диагностическое средство, амидные соединения (варианты), способ получения конъюгата и способы получения амидных соединений | |
| EP2911695B1 (en) | Compositions and methods for the treatment of parkinson disease by the selective delivery of oligonucleotide molecules to specific neuron types | |
| EP4406541A2 (en) | Compositions and methods for decreasing tau expression | |
| JP2016533717A5 (enExample) | ||
| JP2019500346A (ja) | 腎臓病の処置のための組成物と方法 | |
| JP2019500428A5 (enExample) | ||
| US20250051766A1 (en) | Treatment of neurological diseases using modulators of unc13a gene transcripts | |
| CN116655715B (zh) | 一种GalNAc衍生物、缀合物、组合物以及它们的用途 | |
| AU2022402929A1 (en) | Splice switcher antisense oligonucleotides with modified backbone chemistries | |
| WO2019022196A1 (ja) | 一本鎖オリゴヌクレオチド | |
| IL313205A (en) | Microbial symbiosis between a fungus and an alga | |
| TW202102676A (zh) | 調節atxn2表現之寡核苷酸 | |
| WO2022211129A1 (ja) | Ａｔｎ１のアンチセンスオリゴヌクレオチド誘導体 | |
| US20190345496A1 (en) | Antisense oligonucleotides for modulating relb expression | |
| WO2023102548A1 (en) | Treatment of neurological diseases using modulators of kcnq2 gene transcripts | |
| CN119452086A (zh) | 具有修饰的主链化学的gapmer反义寡核苷酸 | |
| JP2023528435A (ja) | 遺伝子転写物のモジュレーターを使用する神経学的疾患の処置 | |
| US20200216845A1 (en) | Antisense oligonucleotides for modulating rela expression | |
| US20190367920A1 (en) | Antisense oligonucleotides for modulating nfkb1 expression | |
| WO2024249791A2 (en) | Modified unc13a oligonucleotides | |
| CN103025357B (zh) | 选择性递送寡核苷酸分子至特定神经元类的组合物和方法 | |
| IL313204A (en) | Methods for the synthesis of complement factor d inhibitors | |
| HK1254822B (en) | Compositions and methods for decreasing tau expression |