ES2847293T3 - Regímenes de tratamiento para el tratamiento de enfermedades neurológicas - Google Patents
Regímenes de tratamiento para el tratamiento de enfermedades neurológicas Download PDFInfo
- Publication number
- ES2847293T3 ES2847293T3 ES10786859T ES10786859T ES2847293T3 ES 2847293 T3 ES2847293 T3 ES 2847293T3 ES 10786859 T ES10786859 T ES 10786859T ES 10786859 T ES10786859 T ES 10786859T ES 2847293 T3 ES2847293 T3 ES 2847293T3
- Authority
- ES
- Spain
- Prior art keywords
- agent
- peptide
- dose
- seq
- use according
- 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.)
- Active
Links
- 238000011282 treatment Methods 0.000 title description 27
- 208000012902 Nervous system disease Diseases 0.000 title description 5
- 208000025966 Neurological disease Diseases 0.000 title description 5
- 238000011269 treatment regimen Methods 0.000 title description 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 145
- 238000001356 surgical procedure Methods 0.000 claims abstract description 40
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims abstract description 34
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims abstract description 34
- 210000004556 brain Anatomy 0.000 claims abstract description 34
- 206010002329 Aneurysm Diseases 0.000 claims abstract description 32
- 230000027455 binding Effects 0.000 claims abstract description 21
- 230000000302 ischemic effect Effects 0.000 claims abstract description 13
- 230000006378 damage Effects 0.000 claims abstract description 12
- 238000002583 angiography Methods 0.000 claims abstract description 9
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 9
- 108700019745 Disks Large Homolog 4 Proteins 0.000 claims abstract description 7
- 102000047174 Disks Large Homolog 4 Human genes 0.000 claims abstract description 7
- 210000004899 c-terminal region Anatomy 0.000 claims abstract description 7
- 210000004027 cell Anatomy 0.000 claims abstract description 7
- AJXONGJARXYRDO-YVNDNENWSA-N (4s)-4-amino-5-[[(2s)-1-[[(2s)-3-carboxy-1-[[(1s)-1-carboxy-2-methylpropyl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CCC(O)=O AJXONGJARXYRDO-YVNDNENWSA-N 0.000 claims abstract description 4
- 230000008499 blood brain barrier function Effects 0.000 claims abstract description 3
- 210000001218 blood-brain barrier Anatomy 0.000 claims abstract description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 109
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 claims description 38
- XWQVQFBTSBCKLI-FKXNDIMNSA-N dnc008987 Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)CNC(=O)[C@@H](N)CC1=CC=C(O)C=C1 XWQVQFBTSBCKLI-FKXNDIMNSA-N 0.000 claims description 38
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 37
- 150000001413 amino acids Chemical group 0.000 claims description 34
- 201000010099 disease Diseases 0.000 claims description 27
- 108010046423 Tat-NR2B9c Proteins 0.000 claims description 25
- 238000001802 infusion Methods 0.000 claims description 25
- 229960001340 histamine Drugs 0.000 claims description 19
- 238000001990 intravenous administration Methods 0.000 claims description 10
- 239000003112 inhibitor Substances 0.000 claims description 9
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 8
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 8
- 238000011260 co-administration Methods 0.000 claims description 6
- 210000003630 histaminocyte Anatomy 0.000 claims description 3
- 230000002311 subsequent effect Effects 0.000 claims description 2
- 238000000034 method Methods 0.000 description 65
- 208000006011 Stroke Diseases 0.000 description 60
- 102000004196 processed proteins & peptides Human genes 0.000 description 51
- 239000002831 pharmacologic agent Substances 0.000 description 47
- 206010061216 Infarction Diseases 0.000 description 37
- 230000007574 infarction Effects 0.000 description 37
- 229940024606 amino acid Drugs 0.000 description 31
- 241000288906 Primates Species 0.000 description 27
- 241001465754 Metazoa Species 0.000 description 24
- 125000003275 alpha amino acid group Chemical group 0.000 description 22
- 210000004204 blood vessel Anatomy 0.000 description 22
- 230000000694 effects Effects 0.000 description 21
- 239000002245 particle Substances 0.000 description 19
- 239000000816 peptidomimetic Substances 0.000 description 18
- 101710149951 Protein Tat Proteins 0.000 description 17
- 208000032382 Ischaemic stroke Diseases 0.000 description 16
- 238000010171 animal model Methods 0.000 description 16
- 230000003993 interaction Effects 0.000 description 15
- 238000002595 magnetic resonance imaging Methods 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 230000003492 excitotoxic effect Effects 0.000 description 14
- 235000018102 proteins Nutrition 0.000 description 14
- 108090000623 proteins and genes Proteins 0.000 description 14
- 102000004169 proteins and genes Human genes 0.000 description 14
- 241000894007 species Species 0.000 description 14
- 102000000470 PDZ domains Human genes 0.000 description 13
- 108050008994 PDZ domains Proteins 0.000 description 13
- 239000003814 drug Substances 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- 231100000063 excitotoxicity Toxicity 0.000 description 12
- 239000000902 placebo Substances 0.000 description 12
- 229940068196 placebo Drugs 0.000 description 12
- 241000700159 Rattus Species 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 206010008118 cerebral infarction Diseases 0.000 description 10
- 208000035475 disorder Diseases 0.000 description 10
- 230000008439 repair process Effects 0.000 description 10
- 210000003169 central nervous system Anatomy 0.000 description 9
- 230000002490 cerebral effect Effects 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 239000008194 pharmaceutical composition Substances 0.000 description 9
- 208000024891 symptom Diseases 0.000 description 9
- 208000032843 Hemorrhage Diseases 0.000 description 8
- 208000016988 Hemorrhagic Stroke Diseases 0.000 description 8
- 230000036772 blood pressure Effects 0.000 description 8
- 230000003902 lesion Effects 0.000 description 8
- 230000001404 mediated effect Effects 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 102100022397 Nitric oxide synthase, brain Human genes 0.000 description 7
- 101710111444 Nitric oxide synthase, brain Proteins 0.000 description 7
- 208000007536 Thrombosis Diseases 0.000 description 7
- 238000009792 diffusion process Methods 0.000 description 7
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 7
- 208000010125 myocardial infarction Diseases 0.000 description 7
- 206010015150 Erythema Diseases 0.000 description 6
- 201000008450 Intracranial aneurysm Diseases 0.000 description 6
- 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 6
- -1 NMDA receptors Chemical compound 0.000 description 6
- 230000001154 acute effect Effects 0.000 description 6
- 230000000254 damaging effect Effects 0.000 description 6
- 238000011161 development Methods 0.000 description 6
- 238000002597 diffusion-weighted imaging Methods 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- 229920001184 polypeptide Polymers 0.000 description 6
- 238000011321 prophylaxis Methods 0.000 description 6
- 201000006474 Brain Ischemia Diseases 0.000 description 5
- 206010008120 Cerebral ischaemia Diseases 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 230000002411 adverse Effects 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 5
- 230000000740 bleeding effect Effects 0.000 description 5
- 108091006116 chimeric peptides Proteins 0.000 description 5
- 238000012544 monitoring process Methods 0.000 description 5
- 230000000926 neurological effect Effects 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 208000022211 Arteriovenous Malformations Diseases 0.000 description 4
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 4
- 150000008574 D-amino acids Chemical class 0.000 description 4
- 208000005189 Embolism Diseases 0.000 description 4
- 102000018899 Glutamate Receptors Human genes 0.000 description 4
- 108010027915 Glutamate Receptors Proteins 0.000 description 4
- 102100022630 Glutamate receptor ionotropic, NMDA 2B Human genes 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 4
- 239000004793 Polystyrene Substances 0.000 description 4
- 208000003251 Pruritus Diseases 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 230000005744 arteriovenous malformation Effects 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 239000011324 bead Substances 0.000 description 4
- 208000021138 brain aneurysm Diseases 0.000 description 4
- 238000007675 cardiac surgery Methods 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 238000001647 drug administration Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 125000005647 linker group Chemical group 0.000 description 4
- 210000002569 neuron Anatomy 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 229920002223 polystyrene Polymers 0.000 description 4
- 238000011809 primate model Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 230000001052 transient effect Effects 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 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 3
- 208000014644 Brain disease Diseases 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- 206010016334 Feeling hot Diseases 0.000 description 3
- 101710195187 Glutamate receptor ionotropic, NMDA 2B Proteins 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- 108700000788 Human immunodeficiency virus 1 tat peptide (47-57) Proteins 0.000 description 3
- 208000004044 Hypesthesia Diseases 0.000 description 3
- 241000282553 Macaca Species 0.000 description 3
- 208000032109 Transient ischaemic attack Diseases 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 210000001367 artery Anatomy 0.000 description 3
- 230000017531 blood circulation Effects 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 230000002612 cardiopulmonary effect Effects 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 230000006866 deterioration Effects 0.000 description 3
- 206010013781 dry mouth Diseases 0.000 description 3
- 230000009540 excitatory neurotransmission Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 208000034783 hypoesthesia Diseases 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 239000004005 microsphere Substances 0.000 description 3
- 230000016273 neuron death Effects 0.000 description 3
- 208000035824 paresthesia Diseases 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 125000006850 spacer group Chemical group 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 201000010875 transient cerebral ischemia Diseases 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- RAVVEEJGALCVIN-AGVBWZICSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-2-[[(2s)-2-[[(2s)-6-amino-2-[[(2s)-6-amino-2-[[(2s)-2-[[2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]hexanoyl]amino]-5-(diamino Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCN=C(N)N)NC(=O)CNC(=O)[C@@H](N)CC1=CC=C(O)C=C1 RAVVEEJGALCVIN-AGVBWZICSA-N 0.000 description 2
- IJJWOSAXNHWBPR-HUBLWGQQSA-N 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-n-(6-hydrazinyl-6-oxohexyl)pentanamide Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)NCCCCCC(=O)NN)SC[C@@H]21 IJJWOSAXNHWBPR-HUBLWGQQSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 108091006146 Channels Proteins 0.000 description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- 208000010201 Exanthema Diseases 0.000 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 description 2
- 208000032984 Intraoperative Complications Diseases 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical group OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 102000004129 N-Type Calcium Channels Human genes 0.000 description 2
- 108090000699 N-Type Calcium Channels Proteins 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 210000002376 aorta thoracic Anatomy 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 230000006931 brain damage Effects 0.000 description 2
- 231100000874 brain damage Toxicity 0.000 description 2
- 208000029028 brain injury Diseases 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 210000001715 carotid artery Anatomy 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 238000002585 cerebral angiography Methods 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000003920 cognitive function Effects 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 238000002591 computed tomography Methods 0.000 description 2
- 210000004351 coronary vessel Anatomy 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- ZSWFCLXCOIISFI-UHFFFAOYSA-N cyclopentadiene Chemical compound C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000002939 deleterious effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- JXSJBGJIGXNWCI-UHFFFAOYSA-N diethyl 2-[(dimethoxyphosphorothioyl)thio]succinate Chemical group CCOC(=O)CC(SP(=S)(OC)OC)C(=O)OCC JXSJBGJIGXNWCI-UHFFFAOYSA-N 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 230000003073 embolic effect Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 201000005884 exanthem Diseases 0.000 description 2
- 231100000318 excitotoxic Toxicity 0.000 description 2
- 210000003414 extremity Anatomy 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 238000011010 flushing procedure Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 230000000642 iatrogenic effect Effects 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- 230000007803 itching Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 230000036244 malformation Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 231100000862 numbness Toxicity 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 206010037844 rash Diseases 0.000 description 2
- 238000011552 rat model Methods 0.000 description 2
- 210000001525 retina Anatomy 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- 230000005945 translocation Effects 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Chemical group OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 210000001364 upper extremity Anatomy 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- VILFTWLXLYIEMV-UHFFFAOYSA-N 1,5-difluoro-2,4-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC([N+]([O-])=O)=C(F)C=C1F VILFTWLXLYIEMV-UHFFFAOYSA-N 0.000 description 1
- VZZPYUKWXDLMGI-UHFFFAOYSA-N 1,6-diisothiocyanatohexane Chemical compound S=C=NCCCCCCN=C=S VZZPYUKWXDLMGI-UHFFFAOYSA-N 0.000 description 1
- IPJGAEWUPXWFPL-UHFFFAOYSA-N 1-[3-(2,5-dioxopyrrol-1-yl)phenyl]pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1C1=CC=CC(N2C(C=CC2=O)=O)=C1 IPJGAEWUPXWFPL-UHFFFAOYSA-N 0.000 description 1
- FXYZDFSNBBOHTA-UHFFFAOYSA-N 2-[amino(morpholin-4-ium-4-ylidene)methyl]guanidine;chloride Chemical compound Cl.NC(N)=NC(=N)N1CCOCC1 FXYZDFSNBBOHTA-UHFFFAOYSA-N 0.000 description 1
- RLFPCLMBTQOMLI-UHFFFAOYSA-N 2-iodo-n-[2-[(2-iodoacetyl)amino]ethyl]acetamide Chemical compound ICC(=O)NCCNC(=O)CI RLFPCLMBTQOMLI-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- 102000003678 AMPA Receptors Human genes 0.000 description 1
- 108090000078 AMPA Receptors Proteins 0.000 description 1
- 208000035657 Abasia Diseases 0.000 description 1
- 108010066676 Abrin Proteins 0.000 description 1
- 108700031308 Antennapedia Homeodomain Proteins 0.000 description 1
- 101100243025 Arabidopsis thaliana PCO2 gene Proteins 0.000 description 1
- 200000000007 Arterial disease Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- 241000193738 Bacillus anthracis Species 0.000 description 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 208000014882 Carotid artery disease Diseases 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010051109 Cell-Penetrating Peptides Proteins 0.000 description 1
- 102000020313 Cell-Penetrating Peptides Human genes 0.000 description 1
- 206010008088 Cerebral artery embolism Diseases 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 206010008132 Cerebral thrombosis Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102000009016 Cholera Toxin Human genes 0.000 description 1
- 108010049048 Cholera Toxin Proteins 0.000 description 1
- 208000002330 Congenital Heart Defects Diseases 0.000 description 1
- 206010056370 Congestive cardiomyopathy Diseases 0.000 description 1
- 101100248440 Danio rerio ric8b gene Proteins 0.000 description 1
- 201000010046 Dilated cardiomyopathy Diseases 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 206010014498 Embolic stroke Diseases 0.000 description 1
- 238000012276 Endovascular treatment Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 101710082714 Exotoxin A Proteins 0.000 description 1
- 238000000729 Fisher's exact test Methods 0.000 description 1
- 229940122459 Glutamate antagonist Drugs 0.000 description 1
- 102100022758 Glutamate receptor ionotropic, kainate 2 Human genes 0.000 description 1
- 101710112360 Glutamate receptor ionotropic, kainate 2 Proteins 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 239000005057 Hexamethylene diisocyanate Substances 0.000 description 1
- 108010070875 Human Immunodeficiency Virus tat Gene Products Proteins 0.000 description 1
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010021639 Incontinence Diseases 0.000 description 1
- 201000001429 Intracranial Thrombosis Diseases 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- 241000282567 Macaca fascicularis Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101000805948 Mus musculus Harmonin Proteins 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 241001504519 Papio ursinus Species 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108010064851 Plant Proteins Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 108010038912 Retinoid X Receptors Proteins 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- 101710192266 Tegument protein VP22 Proteins 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 101150066971 UL49 gene Proteins 0.000 description 1
- 208000009443 Vascular Malformations Diseases 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 208000013404 behavioral symptom Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 206010061592 cardiac fibrillation Diseases 0.000 description 1
- 230000002802 cardiorespiratory effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000000546 chi-square test Methods 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 208000028831 congenital heart disease Diseases 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 210000003618 cortical neuron Anatomy 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 229960000265 cromoglicic acid Drugs 0.000 description 1
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- ZLFRJHOBQVVTOJ-UHFFFAOYSA-N dimethyl hexanediimidate Chemical compound COC(=N)CCCCC(=N)OC ZLFRJHOBQVVTOJ-UHFFFAOYSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 230000002600 fibrillogenic effect Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000003825 glutamate receptor antagonist Substances 0.000 description 1
- 230000009206 glutamatergic signaling Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 208000018578 heart valve disease Diseases 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- RRAMGCGOFNQTLD-UHFFFAOYSA-N hexamethylene diisocyanate Chemical compound O=C=NCCCCCCN=C=O RRAMGCGOFNQTLD-UHFFFAOYSA-N 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000013152 interventional procedure Methods 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 201000010849 intracranial embolism Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000007654 ischemic lesion Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 241001515942 marmosets Species 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 210000003657 middle cerebral artery Anatomy 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- PNQCMZHRTCNQMO-UHFFFAOYSA-N n'-iodooxamide Chemical compound NC(=O)C(=O)NI PNQCMZHRTCNQMO-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000010807 negative regulation of binding Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000007971 neurological deficit Effects 0.000 description 1
- 238000010984 neurological examination Methods 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100001079 no serious adverse effect Toxicity 0.000 description 1
- 238000001208 nuclear magnetic resonance pulse sequence Methods 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 108010043655 penetratin Proteins 0.000 description 1
- MCYTYTUNNNZWOK-LCLOTLQISA-N penetratin Chemical compound C([C@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCCNC(N)=N)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CC=CC=C1 MCYTYTUNNNZWOK-LCLOTLQISA-N 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 238000009520 phase I clinical trial Methods 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 235000021118 plant-derived protein Nutrition 0.000 description 1
- 230000001242 postsynaptic effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 231100000654 protein toxin Toxicity 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 210000005245 right atrium Anatomy 0.000 description 1
- 235000021003 saturated fats Nutrition 0.000 description 1
- 235000021080 saturated-trans fats Nutrition 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 231100000046 skin rash Toxicity 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 230000003977 synaptic function Effects 0.000 description 1
- 230000008625 synaptic signaling Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- PBKWZFANFUTEPS-CWUSWOHSSA-N transportan Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(N)=O)[C@@H](C)CC)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CN)[C@@H](C)O)C1=CC=C(O)C=C1 PBKWZFANFUTEPS-CWUSWOHSSA-N 0.000 description 1
- 108010062760 transportan Proteins 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 230000008736 traumatic injury Effects 0.000 description 1
- 208000037820 vascular cognitive impairment Diseases 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 230000003519 ventilatory effect Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/162—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/10—Fusion polypeptide containing a localisation/targetting motif containing a tag for extracellular membrane crossing, e.g. TAT or VP22
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Virology (AREA)
- Vascular Medicine (AREA)
- Toxicology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Magnetic Resonance Imaging Apparatus (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Management, Administration, Business Operations System, And Electronic Commerce (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US18598909P | 2009-06-10 | 2009-06-10 | |
| PCT/US2010/038200 WO2010144721A2 (en) | 2009-06-10 | 2010-06-10 | Model systems and treatment regimes for treatment of neurological disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2847293T3 true ES2847293T3 (es) | 2021-08-02 |
Family
ID=43309469
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10786859T Active ES2847293T3 (es) | 2009-06-10 | 2010-06-10 | Regímenes de tratamiento para el tratamiento de enfermedades neurológicas |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US8940699B2 (https=) |
| EP (2) | EP2440230B1 (https=) |
| JP (2) | JP6005514B2 (https=) |
| CN (1) | CN102458441A (https=) |
| AU (1) | AU2010258664B2 (https=) |
| BR (1) | BRPI1010718A2 (https=) |
| CA (1) | CA2765169C (https=) |
| DK (1) | DK2440230T3 (https=) |
| ES (1) | ES2847293T3 (https=) |
| HR (1) | HRP20210112T1 (https=) |
| HU (1) | HUE053131T2 (https=) |
| PL (1) | PL2440230T3 (https=) |
| PT (1) | PT2440230T (https=) |
| WO (1) | WO2010144721A2 (https=) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7510824B2 (en) * | 1999-06-02 | 2009-03-31 | Nono Inc. | Method of screening peptides useful in treating traumatic injury to the brain or spinal cord |
| WO2010144721A2 (en) | 2009-06-10 | 2010-12-16 | Arbor Vita Corporation | Model systems and treatment regimes for treatment of neurological disease |
| EP2616094B1 (en) | 2010-08-12 | 2017-11-08 | NoNO Inc. | Treatment of penetrative injury to the brain |
| ES2912042T3 (es) | 2011-06-24 | 2022-05-24 | Nono Inc | Terapia de combinación para isquemia |
| MX364562B (es) * | 2011-12-13 | 2019-04-30 | Nono Inc | Terapia para hemorragia subaracnoidea e isquemia. |
| US9241970B2 (en) | 2011-12-13 | 2016-01-26 | Nono Inc. | Therapy for subarachnoid hemorrhage and ischemia |
| AU2013204309A1 (en) * | 2012-11-13 | 2014-05-29 | Biodiem Limited | Therapeutic Compounds and Uses Thereof |
| US10251935B2 (en) | 2012-11-28 | 2019-04-09 | Nono Inc. | Lyophilized formulation comprising tat-NR2B9C, histidine and trehalose |
| CA2892965C (en) * | 2012-11-28 | 2021-06-01 | Nono Inc. | Lyophilized formulation of tat-nr2b9c |
| WO2015181756A1 (en) | 2014-05-28 | 2015-12-03 | Nono Inc. | Chloride salt of tat-nr2b9c |
| KR102253900B1 (ko) * | 2016-04-27 | 2021-05-18 | 바이오셀즈(베이징) 바이오테크 코., 엘티디. | 흥분성 신경독성 관련 손상 치료용 펩타이드 |
| EP3450446A1 (en) * | 2016-04-27 | 2019-03-06 | Biocells (Beijing) Biotech Co., Ltd. | Treatment method for excitatory neurotoxicity-related injury |
| CN110049994B (zh) * | 2016-12-08 | 2023-05-02 | 拜西欧斯（北京）生物技术有限公司 | 一种缀合物及其应用 |
| WO2019006692A1 (zh) * | 2017-07-05 | 2019-01-10 | 拜西欧斯（北京）生物技术有限公司 | 用于治疗、改善或预防神经系统相关病症的化合物及其用途 |
| KR102403089B1 (ko) * | 2017-07-05 | 2022-06-02 | 바이오셀즈(베이징) 바이오테크 코., 엘티디. | 폴리펩타이드의 약학적으로 허용 가능한 염 및 이의 용도 |
| KR102545825B1 (ko) | 2017-09-30 | 2023-06-22 | 바이오셀즈(베이징) 바이오테크 코., 엘티디. | 흥분성 신경 독성 관련 손상 치료를 위한 펩타이드 조성물 |
| CN113121641B (zh) | 2021-03-11 | 2022-11-01 | 武汉英纳氏药业有限公司 | 一类多功能多肽及其在医药领域的应用 |
| CN113150065B (zh) | 2021-03-11 | 2022-07-08 | 武汉英纳氏药业有限公司 | 一种合成肽及其应用 |
| CN113735938B (zh) | 2021-07-30 | 2024-11-08 | 英纳氏(珠海)药业有限公司 | 一种神经保护多肽化合物及其应用 |
| CN114642402A (zh) * | 2022-03-07 | 2022-06-21 | 翰博瑞强(上海)医药科技有限公司 | 一种用于预测药物对心脏毒性影响的方法及心电图设备 |
| CN114469084B (zh) * | 2022-04-02 | 2022-06-24 | 剑博微电子(深圳)有限公司 | 一种基于高精度adc的血氧监测系统 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060148711A1 (en) | 1999-05-14 | 2006-07-06 | Arbor Vita Corporation | Molecular interactions in neurons |
| US7510824B2 (en) | 1999-06-02 | 2009-03-31 | Nono Inc. | Method of screening peptides useful in treating traumatic injury to the brain or spinal cord |
| GB0025473D0 (en) | 2000-10-17 | 2000-11-29 | Pfizer Ltd | Pharmaceutical combinations |
| WO2004045535A2 (en) * | 2002-11-14 | 2004-06-03 | Arbor Vita Corporation | Molecular interactions in neurons |
| EP1601380A1 (en) | 2003-02-13 | 2005-12-07 | Licentia OY | Use of a mast cell activation or degranulation blocking agent in the manufacture of a medicament for the treatment of cerebral ischemia |
| CA2524573A1 (en) | 2003-05-02 | 2004-11-11 | Paion Deutschland Gmbh | Intravenous injection of non-neurotoxic plasminogen activators for the treatment of stroke |
| DK2043671T3 (da) * | 2006-07-11 | 2020-06-15 | Nono Inc | Peptid og sammensætning deraf til anvendelse ved behandling af slagtilfælde med feber |
| EP1884521A1 (en) * | 2006-07-31 | 2008-02-06 | Xigen S.A. | Fusion peptide for inhibiting interaction of neuronal NMDA receptor (NMDAR) and NMDAR interacting proteins |
| ES2446292T3 (es) * | 2007-03-02 | 2014-03-07 | Nono Inc. | Tratamiento del accidente cerebrovascular y otras enfermedades sin inhibir los canales de calcio de tipo N |
| WO2009006611A1 (en) | 2007-07-03 | 2009-01-08 | Arbor Vita Corporation | Small molecule inhibitors of pdz interactions |
| US8080518B2 (en) | 2007-12-05 | 2011-12-20 | Arbor Vita Corporation | Co-administration of an agent linked to an internalization peptide with an anti-inflammatory |
| DK2320927T3 (en) | 2008-07-09 | 2015-09-14 | Univ Copenhagen | Modified peptides as potent inhibitors of the PSD-95 / NMDA receptor interaction |
| WO2010144721A2 (en) | 2009-06-10 | 2010-12-16 | Arbor Vita Corporation | Model systems and treatment regimes for treatment of neurological disease |
| ES2912042T3 (es) | 2011-06-24 | 2022-05-24 | Nono Inc | Terapia de combinación para isquemia |
| US9241970B2 (en) | 2011-12-13 | 2016-01-26 | Nono Inc. | Therapy for subarachnoid hemorrhage and ischemia |
| MX364562B (es) | 2011-12-13 | 2019-04-30 | Nono Inc | Terapia para hemorragia subaracnoidea e isquemia. |
-
2010
- 2010-06-10 WO PCT/US2010/038200 patent/WO2010144721A2/en not_active Ceased
- 2010-06-10 ES ES10786859T patent/ES2847293T3/es active Active
- 2010-06-10 EP EP10786859.8A patent/EP2440230B1/en active Active
- 2010-06-10 AU AU2010258664A patent/AU2010258664B2/en not_active Ceased
- 2010-06-10 BR BRPI1010718A patent/BRPI1010718A2/pt not_active Application Discontinuation
- 2010-06-10 DK DK10786859.8T patent/DK2440230T3/da active
- 2010-06-10 HR HRP20210112TT patent/HRP20210112T1/hr unknown
- 2010-06-10 CA CA2765169A patent/CA2765169C/en active Active
- 2010-06-10 PL PL10786859T patent/PL2440230T3/pl unknown
- 2010-06-10 JP JP2012515147A patent/JP6005514B2/ja not_active Expired - Fee Related
- 2010-06-10 HU HUE10786859A patent/HUE053131T2/hu unknown
- 2010-06-10 EP EP20200385.1A patent/EP3808366A1/en not_active Withdrawn
- 2010-06-10 US US13/377,523 patent/US8940699B2/en active Active
- 2010-06-10 CN CN2010800352462A patent/CN102458441A/zh active Pending
- 2010-06-10 PT PT107868598T patent/PT2440230T/pt unknown
-
2015
- 2015-01-14 US US14/597,166 patent/US9610323B2/en not_active Expired - Fee Related
- 2015-10-30 JP JP2015214926A patent/JP6220371B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| AU2010258664B2 (en) | 2015-05-28 |
| BRPI1010718A2 (pt) | 2016-03-15 |
| HUE053131T2 (hu) | 2021-06-28 |
| EP2440230B1 (en) | 2020-11-11 |
| PL2440230T3 (pl) | 2021-06-14 |
| JP6005514B2 (ja) | 2016-10-12 |
| JP2012530057A (ja) | 2012-11-29 |
| JP6220371B2 (ja) | 2017-10-25 |
| US20120269733A1 (en) | 2012-10-25 |
| US8940699B2 (en) | 2015-01-27 |
| US20150202253A1 (en) | 2015-07-23 |
| JP2016041731A (ja) | 2016-03-31 |
| HRP20210112T1 (hr) | 2021-04-16 |
| AU2010258664A1 (en) | 2012-01-12 |
| CA2765169A1 (en) | 2010-12-16 |
| PT2440230T (pt) | 2021-02-03 |
| US9610323B2 (en) | 2017-04-04 |
| WO2010144721A2 (en) | 2010-12-16 |
| EP2440230A2 (en) | 2012-04-18 |
| CN102458441A (zh) | 2012-05-16 |
| EP2440230A4 (en) | 2014-05-28 |
| EP3808366A1 (en) | 2021-04-21 |
| WO2010144721A3 (en) | 2011-04-21 |
| CA2765169C (en) | 2019-06-18 |
| DK2440230T3 (da) | 2021-01-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2847293T3 (es) | Regímenes de tratamiento para el tratamiento de enfermedades neurológicas | |
| JP7143374B2 (ja) | 虚血のための組み合わせ療法 | |
| JP6427104B2 (ja) | Ｔａｔ−ＮＲ２Ｂ９ｃの凍結乾燥製剤 | |
| CN104053448B (zh) | 一种蛛网膜下腔出血及局部缺血的治疗方法 | |
| KR20230141958A (ko) | 개선된 치료 지수를 위한 플라스민-내성 펩티드 | |
| AU2021206472A1 (en) | Plasmin-resistant peptides for treating stroke and related conditions | |
| HK40050639A (en) | Treatment regimes for treatment of neurological disease | |
| HK40003366A (en) | Combination therapy for ischemia |