JP7383297B2 - デンドリマー送達システムおよびそれを使用する方法 - Google Patents
デンドリマー送達システムおよびそれを使用する方法 Download PDFInfo
- Publication number
- JP7383297B2 JP7383297B2 JP2020525944A JP2020525944A JP7383297B2 JP 7383297 B2 JP7383297 B2 JP 7383297B2 JP 2020525944 A JP2020525944 A JP 2020525944A JP 2020525944 A JP2020525944 A JP 2020525944A JP 7383297 B2 JP7383297 B2 JP 7383297B2
- Authority
- JP
- Japan
- Prior art keywords
- dendrimer
- groups
- composition
- hydroxymethyl
- agents
- 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
- 239000000412 dendrimer Substances 0.000 title claims description 378
- 229920000736 dendritic polymer Polymers 0.000 title claims description 374
- 238000000034 method Methods 0.000 title claims description 82
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 129
- 239000003814 drug Substances 0.000 claims description 122
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 104
- 239000000203 mixture Substances 0.000 claims description 103
- 210000004556 brain Anatomy 0.000 claims description 79
- 210000004027 cell Anatomy 0.000 claims description 69
- 201000010099 disease Diseases 0.000 claims description 67
- 238000011282 treatment Methods 0.000 claims description 60
- 150000001875 compounds Chemical class 0.000 claims description 51
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical group CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 claims description 44
- 210000003169 central nervous system Anatomy 0.000 claims description 42
- 230000001225 therapeutic effect Effects 0.000 claims description 42
- 125000006850 spacer group Chemical group 0.000 claims description 41
- 230000006378 damage Effects 0.000 claims description 39
- 229920001223 polyethylene glycol Polymers 0.000 claims description 37
- -1 carbosiloxane Chemical compound 0.000 claims description 36
- 229920000962 poly(amidoamine) Polymers 0.000 claims description 35
- 239000000178 monomer Substances 0.000 claims description 27
- 239000000032 diagnostic agent Substances 0.000 claims description 26
- 229940039227 diagnostic agent Drugs 0.000 claims description 26
- 230000000069 prophylactic effect Effects 0.000 claims description 25
- TXBCBTDQIULDIA-UHFFFAOYSA-N 2-[[3-hydroxy-2,2-bis(hydroxymethyl)propoxy]methyl]-2-(hydroxymethyl)propane-1,3-diol Chemical compound OCC(CO)(CO)COCC(CO)(CO)CO TXBCBTDQIULDIA-UHFFFAOYSA-N 0.000 claims description 24
- 206010061218 Inflammation Diseases 0.000 claims description 23
- 210000001642 activated microglia Anatomy 0.000 claims description 23
- 210000001508 eye Anatomy 0.000 claims description 23
- 230000004054 inflammatory process Effects 0.000 claims description 22
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 21
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 21
- PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 claims description 20
- 150000002148 esters Chemical class 0.000 claims description 19
- 229920000858 Cyclodextrin Polymers 0.000 claims description 17
- 210000002540 macrophage Anatomy 0.000 claims description 17
- 229940124597 therapeutic agent Drugs 0.000 claims description 17
- NGYYFWGABVVEPL-UHFFFAOYSA-N 5-(hydroxymethyl)benzene-1,3-diol Chemical compound OCC1=CC(O)=CC(O)=C1 NGYYFWGABVVEPL-UHFFFAOYSA-N 0.000 claims description 16
- SUVIGLJNEAMWEG-UHFFFAOYSA-N propane-1-thiol Chemical compound CCCS SUVIGLJNEAMWEG-UHFFFAOYSA-N 0.000 claims description 16
- XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 claims description 16
- OXBLVCZKDOZZOJ-UHFFFAOYSA-N 2,3-Dihydrothiophene Chemical compound C1CC=CS1 OXBLVCZKDOZZOJ-UHFFFAOYSA-N 0.000 claims description 15
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 15
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 15
- 238000003384 imaging method Methods 0.000 claims description 14
- 229920001661 Chitosan Polymers 0.000 claims description 11
- 229960004308 acetylcysteine Drugs 0.000 claims description 11
- 210000001056 activated astrocyte Anatomy 0.000 claims description 11
- 239000002246 antineoplastic agent Substances 0.000 claims description 11
- 229940127089 cytotoxic agent Drugs 0.000 claims description 11
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical group COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 claims description 10
- 210000001130 astrocyte Anatomy 0.000 claims description 10
- WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 claims description 10
- 238000002296 dynamic light scattering Methods 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- QHQZEEGNGSZBOL-UHFFFAOYSA-N 2-(aminomethyl)-2-(hydroxymethyl)propane-1,3-diol Chemical compound NCC(CO)(CO)CO QHQZEEGNGSZBOL-UHFFFAOYSA-N 0.000 claims description 8
- RRQXXKCYECDESZ-UHFFFAOYSA-N 2-[3-(2-hydroxyethoxy)-2,2-bis(2-hydroxyethoxymethyl)propoxy]ethanol Chemical compound OCCOCC(COCCO)(COCCO)COCCO RRQXXKCYECDESZ-UHFFFAOYSA-N 0.000 claims description 8
- QOYZWSPUVHSVFK-UHFFFAOYSA-N 3,3-bis(ethenyl)penta-1,4-diene Chemical compound C=CC(C=C)(C=C)C=C QOYZWSPUVHSVFK-UHFFFAOYSA-N 0.000 claims description 8
- CQOIYSASVHVTBU-UHFFFAOYSA-N 3-(Carboxymethyl)-3-hydroxypentanedioic acid Chemical compound OC(=O)CC(O)(CC(O)=O)CC(O)=O CQOIYSASVHVTBU-UHFFFAOYSA-N 0.000 claims description 8
- CJLDYMAZKTWCBP-UHFFFAOYSA-N 3-(hydroxymethyl)-5,5-dimethylhexane-2,4-diol Chemical compound CC(O)C(CO)C(O)C(C)(C)C CJLDYMAZKTWCBP-UHFFFAOYSA-N 0.000 claims description 8
- IWTIBPIVCKUAHK-UHFFFAOYSA-N 3-[bis(2-carboxyethyl)amino]propanoic acid Chemical compound OC(=O)CCN(CCC(O)=O)CCC(O)=O IWTIBPIVCKUAHK-UHFFFAOYSA-N 0.000 claims description 8
- BRPSWMCDEYMRPE-UHFFFAOYSA-N 4-[1,1-bis(4-hydroxyphenyl)ethyl]phenol Chemical compound C=1C=C(O)C=CC=1C(C=1C=CC(O)=CC=1)(C)C1=CC=C(O)C=C1 BRPSWMCDEYMRPE-UHFFFAOYSA-N 0.000 claims description 8
- JUDVWZSPIDFZLA-UHFFFAOYSA-N 5-(hydroxymethyl)benzene-1,2,3-triol Chemical compound OCC1=CC(O)=C(O)C(O)=C1 JUDVWZSPIDFZLA-UHFFFAOYSA-N 0.000 claims description 8
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 claims description 8
- 239000001116 FEMA 4028 Substances 0.000 claims description 8
- ZJCCRDAZUWHFQH-UHFFFAOYSA-N Trimethylolpropane Chemical compound CCC(CO)(CO)CO ZJCCRDAZUWHFQH-UHFFFAOYSA-N 0.000 claims description 8
- DKFZANBRNAIQGJ-UHFFFAOYSA-N [3,5-bis[ethenyl(dimethyl)silyl]phenyl]-ethenyl-dimethylsilane Chemical compound C=C[Si](C)(C)C1=CC([Si](C)(C)C=C)=CC([Si](C)(C)C=C)=C1 DKFZANBRNAIQGJ-UHFFFAOYSA-N 0.000 claims description 8
- ITBPIKUGMIZTJR-UHFFFAOYSA-N [bis(hydroxymethyl)amino]methanol Chemical compound OCN(CO)CO ITBPIKUGMIZTJR-UHFFFAOYSA-N 0.000 claims description 8
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 claims description 8
- 229940043377 alpha-cyclodextrin Drugs 0.000 claims description 8
- 150000001408 amides Chemical class 0.000 claims description 8
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 claims description 8
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims description 8
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims description 8
- 229960004853 betadex Drugs 0.000 claims description 8
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 claims description 8
- 230000007062 hydrolysis Effects 0.000 claims description 8
- 238000006460 hydrolysis reaction Methods 0.000 claims description 8
- 150000002772 monosaccharides Chemical class 0.000 claims description 8
- HRJHMASEOAFJRE-UHFFFAOYSA-N n-(2-aminoethyl)-3-[bis[3-(2-aminoethylamino)-3-oxopropyl]amino]propanamide Chemical compound NCCNC(=O)CCN(CCC(=O)NCCN)CCC(=O)NCCN HRJHMASEOAFJRE-UHFFFAOYSA-N 0.000 claims description 8
- 229920001542 oligosaccharide Polymers 0.000 claims description 8
- 150000002482 oligosaccharides Chemical class 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 claims description 8
- 210000003583 retinal pigment epithelium Anatomy 0.000 claims description 8
- RNGMXONQPNPDFK-UHFFFAOYSA-N tetrakis(3-trichlorosilylpropyl)silane Chemical compound Cl[Si](Cl)(Cl)CCC[Si](CCC[Si](Cl)(Cl)Cl)(CCC[Si](Cl)(Cl)Cl)CCC[Si](Cl)(Cl)Cl RNGMXONQPNPDFK-UHFFFAOYSA-N 0.000 claims description 8
- 150000004043 trisaccharides Chemical class 0.000 claims description 8
- 239000002202 Polyethylene glycol Substances 0.000 claims description 7
- 230000001268 conjugating effect Effects 0.000 claims description 7
- MSBXTPRURXJCPF-DQWIULQBSA-N cucurbit[6]uril Chemical compound N1([C@@H]2[C@@H]3N(C1=O)CN1[C@@H]4[C@@H]5N(C1=O)CN1[C@@H]6[C@@H]7N(C1=O)CN1[C@@H]8[C@@H]9N(C1=O)CN([C@H]1N(C%10=O)CN9C(=O)N8CN7C(=O)N6CN5C(=O)N4CN3C(=O)N2C2)C3=O)CN4C(=O)N5[C@@H]6[C@H]4N2C(=O)N6CN%10[C@H]1N3C5 MSBXTPRURXJCPF-DQWIULQBSA-N 0.000 claims description 7
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 claims description 7
- 229940080345 gamma-cyclodextrin Drugs 0.000 claims description 7
- 150000007970 thio esters Chemical class 0.000 claims description 7
- KNISWVDCZKAUQC-UHFFFAOYSA-N 3-[(3-amino-3-oxopropyl)-[2-[bis(3-amino-3-oxopropyl)amino]ethyl]amino]propanamide Chemical compound NC(=O)CCN(CCC(N)=O)CCN(CCC(N)=O)CCC(N)=O KNISWVDCZKAUQC-UHFFFAOYSA-N 0.000 claims description 6
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 6
- 150000002016 disaccharides Chemical class 0.000 claims description 6
- 230000009467 reduction Effects 0.000 claims description 6
- 238000006722 reduction reaction Methods 0.000 claims description 6
- 229960005475 antiinfective agent Drugs 0.000 claims description 5
- 239000004599 antimicrobial Substances 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 238000007254 oxidation reaction Methods 0.000 claims description 5
- MWKXKDBZZAVWKS-UHFFFAOYSA-N diazonio-[1-hydroxy-2-[2-(2-hydroxyethoxy)ethoxy]ethyl]azanide Chemical compound OCCOCCOCC(O)N=[N+]=[N-] MWKXKDBZZAVWKS-UHFFFAOYSA-N 0.000 claims description 4
- 230000003647 oxidation Effects 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 229940124549 vasodilator Drugs 0.000 claims description 4
- 239000003071 vasodilator agent Substances 0.000 claims description 4
- NVGVNJDFTHQFQR-UHFFFAOYSA-N benzene-1,2,3,4,5,6-hexathiol Chemical compound SC1=C(S)C(S)=C(S)C(S)=C1S NVGVNJDFTHQFQR-UHFFFAOYSA-N 0.000 claims description 3
- 150000002019 disulfides Chemical class 0.000 claims description 3
- 238000006702 propargylation reaction Methods 0.000 claims description 3
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 claims description 2
- 150000004657 carbamic acid derivatives Chemical class 0.000 claims description 2
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 2
- 150000002170 ethers Chemical class 0.000 claims description 2
- 150000002429 hydrazines Chemical class 0.000 claims description 2
- 229920001353 Dextrin Polymers 0.000 claims 1
- 239000004375 Dextrin Substances 0.000 claims 1
- 235000019425 dextrin Nutrition 0.000 claims 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 213
- 229940079593 drug Drugs 0.000 description 97
- 206010008129 cerebral palsy Diseases 0.000 description 65
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- 241000283973 Oryctolagus cuniculus Species 0.000 description 59
- 239000000243 solution Substances 0.000 description 59
- 238000006243 chemical reaction Methods 0.000 description 51
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 51
- 239000011541 reaction mixture Substances 0.000 description 49
- 239000013543 active substance Substances 0.000 description 48
- 239000003795 chemical substances by application Substances 0.000 description 43
- 229910001868 water Inorganic materials 0.000 description 43
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 41
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 41
- 230000015572 biosynthetic process Effects 0.000 description 41
- 125000005647 linker group Chemical group 0.000 description 41
- 238000002360 preparation method Methods 0.000 description 37
- 208000035475 disorder Diseases 0.000 description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- 206010028980 Neoplasm Diseases 0.000 description 33
- 210000001519 tissue Anatomy 0.000 description 33
- 210000000274 microglia Anatomy 0.000 description 32
- 238000003786 synthesis reaction Methods 0.000 description 32
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 31
- 208000027418 Wounds and injury Diseases 0.000 description 30
- 208000014674 injury Diseases 0.000 description 30
- 230000008499 blood brain barrier function Effects 0.000 description 29
- 210000001218 blood-brain barrier Anatomy 0.000 description 29
- 208000036110 Neuroinflammatory disease Diseases 0.000 description 27
- 239000002158 endotoxin Substances 0.000 description 26
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 25
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 25
- 239000007924 injection Substances 0.000 description 25
- 238000002347 injection Methods 0.000 description 25
- 229920006008 lipopolysaccharide Polymers 0.000 description 25
- 239000002904 solvent Substances 0.000 description 25
- 238000000502 dialysis Methods 0.000 description 23
- 229920000642 polymer Polymers 0.000 description 23
- 238000009826 distribution Methods 0.000 description 22
- 238000001727 in vivo Methods 0.000 description 22
- 230000003959 neuroinflammation Effects 0.000 description 22
- 230000008685 targeting Effects 0.000 description 22
- 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 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
- 210000000056 organ Anatomy 0.000 description 20
- 239000000126 substance Substances 0.000 description 20
- 239000002953 phosphate buffered saline Substances 0.000 description 19
- 208000002780 macular degeneration Diseases 0.000 description 18
- 239000000463 material Substances 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
- 239000002105 nanoparticle Substances 0.000 description 17
- 208000024891 symptom Diseases 0.000 description 17
- 241001465754 Metazoa Species 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 16
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 16
- 206010064930 age-related macular degeneration Diseases 0.000 description 16
- 230000003110 anti-inflammatory effect Effects 0.000 description 16
- 238000004128 high performance liquid chromatography Methods 0.000 description 16
- 210000001320 hippocampus Anatomy 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- 238000005481 NMR spectroscopy Methods 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- 239000003112 inhibitor Substances 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 210000004885 white matter Anatomy 0.000 description 15
- 238000013459 approach Methods 0.000 description 14
- 230000021615 conjugation Effects 0.000 description 14
- 125000000524 functional group Chemical group 0.000 description 14
- 208000005017 glioblastoma Diseases 0.000 description 14
- 108090000623 proteins and genes Proteins 0.000 description 14
- 230000003078 antioxidant effect Effects 0.000 description 13
- 239000007864 aqueous solution Substances 0.000 description 13
- 235000018102 proteins Nutrition 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 12
- 208000012902 Nervous system disease Diseases 0.000 description 12
- 239000003963 antioxidant agent Substances 0.000 description 12
- 235000006708 antioxidants Nutrition 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
- 241000699666 Mus <mouse, genus> Species 0.000 description 11
- 208000025966 Neurological disease Diseases 0.000 description 11
- 102000008233 Toll-Like Receptor 4 Human genes 0.000 description 11
- 108010060804 Toll-Like Receptor 4 Proteins 0.000 description 11
- 230000004888 barrier function Effects 0.000 description 11
- 208000015114 central nervous system disease Diseases 0.000 description 11
- 210000003734 kidney Anatomy 0.000 description 11
- 208000036546 leukodystrophy Diseases 0.000 description 11
- 229960004640 memantine Drugs 0.000 description 11
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 11
- 230000004770 neurodegeneration Effects 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 210000002381 plasma Anatomy 0.000 description 11
- 230000000770 proinflammatory effect Effects 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- 210000001525 retina Anatomy 0.000 description 11
- 238000002560 therapeutic procedure Methods 0.000 description 11
- 210000004981 tumor-associated macrophage Anatomy 0.000 description 11
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 10
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 230000035508 accumulation Effects 0.000 description 10
- 238000009825 accumulation Methods 0.000 description 10
- 208000002352 blister Diseases 0.000 description 10
- 201000011510 cancer Diseases 0.000 description 10
- 238000012650 click reaction Methods 0.000 description 10
- 229940125851 compound 27 Drugs 0.000 description 10
- 239000002872 contrast media Substances 0.000 description 10
- 210000000877 corpus callosum Anatomy 0.000 description 10
- 230000018109 developmental process Effects 0.000 description 10
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 10
- 238000001990 intravenous administration Methods 0.000 description 10
- 150000002632 lipids Chemical class 0.000 description 10
- 210000004185 liver Anatomy 0.000 description 10
- 238000011068 loading method Methods 0.000 description 10
- 208000015122 neurodegenerative disease Diseases 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 201000011452 Adrenoleukodystrophy Diseases 0.000 description 9
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 9
- 208000035478 Interatrial communication Diseases 0.000 description 9
- 108090001005 Interleukin-6 Proteins 0.000 description 9
- 102000004889 Interleukin-6 Human genes 0.000 description 9
- 208000034800 Leukoencephalopathies Diseases 0.000 description 9
- 208000029726 Neurodevelopmental disease Diseases 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 9
- 206010003664 atrial septal defect Diseases 0.000 description 9
- 230000001588 bifunctional effect Effects 0.000 description 9
- 238000011161 development Methods 0.000 description 9
- 238000005516 engineering process Methods 0.000 description 9
- 230000014509 gene expression Effects 0.000 description 9
- 230000001771 impaired effect Effects 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 238000002483 medication Methods 0.000 description 9
- 210000004498 neuroglial cell Anatomy 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 208000003174 Brain Neoplasms Diseases 0.000 description 8
- 206010012289 Dementia Diseases 0.000 description 8
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 8
- 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 8
- HAXFWIACAGNFHA-UHFFFAOYSA-N aldrithiol Chemical compound C=1C=CC=NC=1SSC1=CC=CC=N1 HAXFWIACAGNFHA-UHFFFAOYSA-N 0.000 description 8
- 239000008121 dextrose Substances 0.000 description 8
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 8
- 230000003492 excitotoxic effect Effects 0.000 description 8
- 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 description 8
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical group NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 8
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 8
- 210000002216 heart Anatomy 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
- 238000010253 intravenous injection Methods 0.000 description 8
- 210000003140 lateral ventricle Anatomy 0.000 description 8
- 210000004072 lung Anatomy 0.000 description 8
- 230000014759 maintenance of location Effects 0.000 description 8
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 8
- 239000002609 medium Substances 0.000 description 8
- SENLDUJVTGGYIH-UHFFFAOYSA-N n-(2-aminoethyl)-3-[[3-(2-aminoethylamino)-3-oxopropyl]-[2-[bis[3-(2-aminoethylamino)-3-oxopropyl]amino]ethyl]amino]propanamide Chemical compound NCCNC(=O)CCN(CCC(=O)NCCN)CCN(CCC(=O)NCCN)CCC(=O)NCCN SENLDUJVTGGYIH-UHFFFAOYSA-N 0.000 description 8
- 210000000653 nervous system Anatomy 0.000 description 8
- 238000011555 rabbit model Methods 0.000 description 8
- 150000003384 small molecules Chemical class 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- JWDFQMWEFLOOED-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(pyridin-2-yldisulfanyl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSC1=CC=CC=N1 JWDFQMWEFLOOED-UHFFFAOYSA-N 0.000 description 7
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 7
- 229920002307 Dextran Polymers 0.000 description 7
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
- 230000003542 behavioural effect Effects 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- 238000012377 drug delivery Methods 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 208000015181 infectious disease Diseases 0.000 description 7
- 108020004999 messenger RNA Proteins 0.000 description 7
- 230000002025 microglial effect Effects 0.000 description 7
- 238000010172 mouse model Methods 0.000 description 7
- 230000036542 oxidative stress Effects 0.000 description 7
- 239000002245 particle Substances 0.000 description 7
- 230000007170 pathology Effects 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 230000002207 retinal effect Effects 0.000 description 7
- 238000012552 review Methods 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 6
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 6
- 208000024827 Alzheimer disease Diseases 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 241000283707 Capra Species 0.000 description 6
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 6
- 108090001090 Lectins Proteins 0.000 description 6
- 102000004856 Lectins Human genes 0.000 description 6
- 206010051606 Necrotising colitis Diseases 0.000 description 6
- 208000018737 Parkinson disease Diseases 0.000 description 6
- FTALBRSUTCGOEG-UHFFFAOYSA-N Riluzole Chemical compound C1=C(OC(F)(F)F)C=C2SC(N)=NC2=C1 FTALBRSUTCGOEG-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 6
- 229960003805 amantadine Drugs 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 239000000164 antipsychotic agent Substances 0.000 description 6
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 6
- 210000004204 blood vessel Anatomy 0.000 description 6
- 208000029028 brain injury Diseases 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 210000003161 choroid Anatomy 0.000 description 6
- 230000008045 co-localization Effects 0.000 description 6
- 229940125833 compound 23 Drugs 0.000 description 6
- 238000010511 deprotection reaction Methods 0.000 description 6
- 238000007876 drug discovery Methods 0.000 description 6
- QELUYTUMUWHWMC-UHFFFAOYSA-N edaravone Chemical compound O=C1CC(C)=NN1C1=CC=CC=C1 QELUYTUMUWHWMC-UHFFFAOYSA-N 0.000 description 6
- 238000001506 fluorescence spectroscopy Methods 0.000 description 6
- 239000012634 fragment Substances 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 6
- 229930195712 glutamate Natural products 0.000 description 6
- 206010023332 keratitis Diseases 0.000 description 6
- 239000002523 lectin Substances 0.000 description 6
- 239000002539 nanocarrier Substances 0.000 description 6
- 208000004995 necrotizing enterocolitis Diseases 0.000 description 6
- 230000000926 neurological effect Effects 0.000 description 6
- 108020004707 nucleic acids Proteins 0.000 description 6
- 102000039446 nucleic acids Human genes 0.000 description 6
- 150000007523 nucleic acids Chemical class 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 201000006195 perinatal necrotizing enterocolitis Diseases 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 238000011002 quantification Methods 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 235000000346 sugar Nutrition 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 208000011580 syndromic disease Diseases 0.000 description 6
- 230000009885 systemic effect Effects 0.000 description 6
- 230000032258 transport Effects 0.000 description 6
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 5
- 102000004127 Cytokines Human genes 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 5
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 5
- 208000023105 Huntington disease Diseases 0.000 description 5
- 108090000174 Interleukin-10 Proteins 0.000 description 5
- 102000003814 Interleukin-10 Human genes 0.000 description 5
- 108090000978 Interleukin-4 Proteins 0.000 description 5
- 201000002832 Lewy body dementia Diseases 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 5
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 5
- 229940005529 antipsychotics Drugs 0.000 description 5
- 210000005013 brain tissue Anatomy 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 230000003833 cell viability Effects 0.000 description 5
- 150000005829 chemical entities Chemical class 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 229940127573 compound 38 Drugs 0.000 description 5
- NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 5
- 230000008034 disappearance Effects 0.000 description 5
- 239000000839 emulsion Substances 0.000 description 5
- 208000030533 eye disease Diseases 0.000 description 5
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 5
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 5
- 230000001976 improved effect Effects 0.000 description 5
- 230000005865 ionizing radiation Effects 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 239000002480 mineral oil Substances 0.000 description 5
- 235000010446 mineral oil Nutrition 0.000 description 5
- 230000003188 neurobehavioral effect Effects 0.000 description 5
- 210000002569 neuron Anatomy 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 5
- 230000036407 pain Effects 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- 229960002930 sirolimus Drugs 0.000 description 5
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 5
- 229960000604 valproic acid Drugs 0.000 description 5
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 5
- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 4
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 4
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 4
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 4
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 4
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 4
- PTBDIHRZYDMNKB-UHFFFAOYSA-N 2,2-Bis(hydroxymethyl)propionic acid Chemical compound OCC(C)(CO)C(O)=O PTBDIHRZYDMNKB-UHFFFAOYSA-N 0.000 description 4
- NPRYCHLHHVWLQZ-TURQNECASA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynylpurin-8-one Chemical compound NC1=NC=C2N(C(N(C2=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C NPRYCHLHHVWLQZ-TURQNECASA-N 0.000 description 4
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- LPWKFUVWWQYLOD-UHFFFAOYSA-N 9-(dimethylamino)-3-(4-methylphenyl)pyrido[2,3]thieno[2,4-d]pyrimidin-4-one Chemical compound C1=2C(N(C)C)=CN=CC=2SC(C2=O)=C1N=CN2C1=CC=C(C)C=C1 LPWKFUVWWQYLOD-UHFFFAOYSA-N 0.000 description 4
- 102100024643 ATP-binding cassette sub-family D member 1 Human genes 0.000 description 4
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 4
- QLMMOGWZCFQAPU-UHFFFAOYSA-N CGP-3466 Chemical compound C#CCN(C)CC1=CC2=CC=CC=C2OC2=CC=CC=C12 QLMMOGWZCFQAPU-UHFFFAOYSA-N 0.000 description 4
- 229940126639 Compound 33 Drugs 0.000 description 4
- 229940127007 Compound 39 Drugs 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 4
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 4
- 208000010055 Globoid Cell Leukodystrophy Diseases 0.000 description 4
- 108010024636 Glutathione Proteins 0.000 description 4
- 102000003964 Histone deacetylase Human genes 0.000 description 4
- 108090000353 Histone deacetylase Proteins 0.000 description 4
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 4
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 4
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 4
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 4
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 4
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 4
- 108010049137 Member 1 Subfamily D ATP Binding Cassette Transporter Proteins 0.000 description 4
- 201000011442 Metachromatic leukodystrophy Diseases 0.000 description 4
- 101100260702 Mus musculus Tinagl1 gene Proteins 0.000 description 4
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 4
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 4
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 4
- 208000022873 Ocular disease Diseases 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 208000020547 Peroxisomal disease Diseases 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 4
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- BHTRKEVKTKCXOH-UHFFFAOYSA-N Taurochenodesoxycholsaeure Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCCS(O)(=O)=O)C)C1(C)CC2 BHTRKEVKTKCXOH-UHFFFAOYSA-N 0.000 description 4
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 4
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 4
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 4
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 4
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 4
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 4
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 229940124599 anti-inflammatory drug Drugs 0.000 description 4
- 229940088710 antibiotic agent Drugs 0.000 description 4
- 239000000935 antidepressant agent Substances 0.000 description 4
- 229940005513 antidepressants Drugs 0.000 description 4
- 230000006907 apoptotic process Effects 0.000 description 4
- 101150088826 arg1 gene Proteins 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 4
- 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 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004155 blood-retinal barrier Anatomy 0.000 description 4
- 230000004378 blood-retinal barrier Effects 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 239000000544 cholinesterase inhibitor Substances 0.000 description 4
- 229960004170 clozapine Drugs 0.000 description 4
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 4
- 208000010877 cognitive disease Diseases 0.000 description 4
- 229940126086 compound 21 Drugs 0.000 description 4
- 229940126208 compound 22 Drugs 0.000 description 4
- 229940125846 compound 25 Drugs 0.000 description 4
- 229940126214 compound 3 Drugs 0.000 description 4
- 229940125878 compound 36 Drugs 0.000 description 4
- 238000010226 confocal imaging Methods 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 239000010949 copper Substances 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- FASDKYOPVNHBLU-SSDOTTSWSA-N dexpramipexole Chemical compound C1[C@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-SSDOTTSWSA-N 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- 125000002228 disulfide group Chemical group 0.000 description 4
- 229960003530 donepezil Drugs 0.000 description 4
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 4
- 229940093471 ethyl oleate Drugs 0.000 description 4
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 4
- 231100000318 excitotoxic Toxicity 0.000 description 4
- 231100000063 excitotoxicity Toxicity 0.000 description 4
- 230000001747 exhibiting effect Effects 0.000 description 4
- 229930195729 fatty acid Natural products 0.000 description 4
- 239000000194 fatty acid Substances 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 229960003980 galantamine Drugs 0.000 description 4
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 229960003180 glutathione Drugs 0.000 description 4
- 230000004886 head movement Effects 0.000 description 4
- 208000013403 hyperactivity Diseases 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 238000003364 immunohistochemistry Methods 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 239000000411 inducer Substances 0.000 description 4
- 208000027866 inflammatory disease Diseases 0.000 description 4
- 229960003299 ketamine Drugs 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 229960004502 levodopa Drugs 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000033001 locomotion Effects 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 229960001785 mirtazapine Drugs 0.000 description 4
- RONZAEMNMFQXRA-UHFFFAOYSA-N mirtazapine Chemical compound C1C2=CC=CN=C2N2CCN(C)CC2C2=CC=CC=C21 RONZAEMNMFQXRA-UHFFFAOYSA-N 0.000 description 4
- 230000001537 neural effect Effects 0.000 description 4
- 239000004090 neuroprotective agent Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 230000000737 periodic effect Effects 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 4
- 229920000333 poly(propyleneimine) Polymers 0.000 description 4
- 229920000728 polyester Polymers 0.000 description 4
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 4
- 208000020016 psychiatric disease Diseases 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 238000001959 radiotherapy Methods 0.000 description 4
- 239000003642 reactive oxygen metabolite Substances 0.000 description 4
- 238000003753 real-time PCR Methods 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 229960004136 rivastigmine Drugs 0.000 description 4
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 4
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 230000009747 swallowing Effects 0.000 description 4
- 229960001685 tacrine Drugs 0.000 description 4
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 4
- BHTRKEVKTKCXOH-LBSADWJPSA-N tauroursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)CC1 BHTRKEVKTKCXOH-LBSADWJPSA-N 0.000 description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- 150000004669 very long chain fatty acids Chemical class 0.000 description 4
- 230000004584 weight gain Effects 0.000 description 4
- 235000019786 weight gain Nutrition 0.000 description 4
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 3
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 3
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 3
- MVUPXBLYWCSBJH-QMMMGPOBSA-N (2R)-2-acetamido-3-[[3-(2,5-dioxopyrrolidin-1-yl)oxy-3-oxopropyl]disulfanyl]propanoic acid Chemical compound C(C)(=O)N[C@@H](CSSCCC(=O)ON1C(CCC1=O)=O)C(=O)O MVUPXBLYWCSBJH-QMMMGPOBSA-N 0.000 description 3
- ZADWXFSZEAPBJS-SNVBAGLBSA-N (2r)-2-amino-3-(1-methylindol-3-yl)propanoic acid Chemical compound C1=CC=C2N(C)C=C(C[C@@H](N)C(O)=O)C2=C1 ZADWXFSZEAPBJS-SNVBAGLBSA-N 0.000 description 3
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 3
- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 3
- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 3
- FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 description 3
- KWVGIHKZDCUPEU-UHFFFAOYSA-N 2,2-dimethoxy-2-phenylacetophenone Chemical compound C=1C=CC=CC=1C(OC)(OC)C(=O)C1=CC=CC=C1 KWVGIHKZDCUPEU-UHFFFAOYSA-N 0.000 description 3
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 3
- ACUIFAAXWDLLTR-UHFFFAOYSA-N 4-(9h-fluoren-9-ylmethoxycarbonylamino)butanoic acid Chemical compound C1=CC=C2C(COC(=O)NCCCC(=O)O)C3=CC=CC=C3C2=C1 ACUIFAAXWDLLTR-UHFFFAOYSA-N 0.000 description 3
- HIDJWBGOQFTDLU-UHFFFAOYSA-N 4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)(C)OC(=O)NCCCC(O)=O HIDJWBGOQFTDLU-UHFFFAOYSA-N 0.000 description 3
- 102100022146 Arylsulfatase A Human genes 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- 229930186147 Cephalosporin Natural products 0.000 description 3
- 206010008025 Cerebellar ataxia Diseases 0.000 description 3
- 108010036867 Cerebroside-Sulfatase Proteins 0.000 description 3
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 description 3
- 108020004635 Complementary DNA Proteins 0.000 description 3
- 229940126657 Compound 17 Drugs 0.000 description 3
- 206010012689 Diabetic retinopathy Diseases 0.000 description 3
- 108090000371 Esterases Proteins 0.000 description 3
- RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 3
- 102100028496 Galactocerebrosidase Human genes 0.000 description 3
- 108010042681 Galactosylceramidase Proteins 0.000 description 3
- 208000021236 Hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia Diseases 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101000998969 Homo sapiens Inositol-3-phosphate synthase 1 Proteins 0.000 description 3
- 102100036881 Inositol-3-phosphate synthase 1 Human genes 0.000 description 3
- 208000028226 Krabbe disease Diseases 0.000 description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 3
- 208000009829 Lewy Body Disease Diseases 0.000 description 3
- 208000001089 Multiple system atrophy Diseases 0.000 description 3
- 229940127523 NMDA Receptor Antagonists Drugs 0.000 description 3
- 239000007832 Na2SO4 Substances 0.000 description 3
- 208000018909 Neonatal adrenoleukodystrophy Diseases 0.000 description 3
- 229930182555 Penicillin Natural products 0.000 description 3
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 206010046851 Uveitis Diseases 0.000 description 3
- 208000010796 X-linked adrenoleukodystrophy Diseases 0.000 description 3
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 230000032683 aging Effects 0.000 description 3
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000001430 anti-depressive effect Effects 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 3
- 150000001540 azides Chemical class 0.000 description 3
- 229960004669 basiliximab Drugs 0.000 description 3
- 239000012620 biological material Substances 0.000 description 3
- 238000010804 cDNA synthesis Methods 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 235000011089 carbon dioxide Nutrition 0.000 description 3
- 230000022131 cell cycle Effects 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 229940124587 cephalosporin Drugs 0.000 description 3
- 150000001780 cephalosporins Chemical class 0.000 description 3
- 230000002490 cerebral effect Effects 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 230000004087 circulation Effects 0.000 description 3
- 238000011278 co-treatment Methods 0.000 description 3
- 235000017471 coenzyme Q10 Nutrition 0.000 description 3
- 229940110767 coenzyme Q10 Drugs 0.000 description 3
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 239000002131 composite material Substances 0.000 description 3
- 229940125773 compound 10 Drugs 0.000 description 3
- 229940126543 compound 14 Drugs 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- 229940125961 compound 24 Drugs 0.000 description 3
- 238000004624 confocal microscopy Methods 0.000 description 3
- LBJNMUFDOHXDFG-UHFFFAOYSA-N copper;hydrate Chemical compound O.[Cu].[Cu] LBJNMUFDOHXDFG-UHFFFAOYSA-N 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 229960002806 daclizumab Drugs 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical class C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 3
- LBOJYSIDWZQNJS-CVEARBPZSA-N dizocilpine Chemical compound C12=CC=CC=C2[C@]2(C)C3=CC=CC=C3C[C@H]1N2 LBOJYSIDWZQNJS-CVEARBPZSA-N 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 238000005227 gel permeation chromatography Methods 0.000 description 3
- 238000001476 gene delivery Methods 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 229920000587 hyperbranched polymer Polymers 0.000 description 3
- 230000002519 immonomodulatory effect Effects 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 238000009169 immunotherapy Methods 0.000 description 3
- 230000002458 infectious effect Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 210000002425 internal capsule Anatomy 0.000 description 3
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 3
- 230000013016 learning Effects 0.000 description 3
- 239000012669 liquid formulation Substances 0.000 description 3
- 230000004807 localization Effects 0.000 description 3
- 230000008774 maternal effect Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 3
- 230000006775 microglial inflammation Effects 0.000 description 3
- 235000013336 milk Nutrition 0.000 description 3
- 239000008267 milk Substances 0.000 description 3
- 210000004080 milk Anatomy 0.000 description 3
- 229960004023 minocycline Drugs 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 239000012120 mounting media Substances 0.000 description 3
- 201000006417 multiple sclerosis Diseases 0.000 description 3
- 210000005036 nerve Anatomy 0.000 description 3
- 210000004940 nucleus Anatomy 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 229940049954 penicillin Drugs 0.000 description 3
- 229920000570 polyether Polymers 0.000 description 3
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 239000012264 purified product Substances 0.000 description 3
- 239000002534 radiation-sensitizing agent Substances 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 229960003876 ranibizumab Drugs 0.000 description 3
- 238000011552 rat model Methods 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 229960004641 rituximab Drugs 0.000 description 3
- 238000002390 rotary evaporation Methods 0.000 description 3
- 229960002073 sertraline Drugs 0.000 description 3
- 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 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 210000000278 spinal cord Anatomy 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- 229960005322 streptomycin Drugs 0.000 description 3
- 230000035882 stress Effects 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 239000003053 toxin Substances 0.000 description 3
- 231100000765 toxin Toxicity 0.000 description 3
- 108700012359 toxins Proteins 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 239000003039 volatile agent Substances 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- 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 2
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 2
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 2
- MKJIEFSOBYUXJB-HOCLYGCPSA-N (3S,11bS)-9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical compound C1CN2C[C@H](CC(C)C)C(=O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-HOCLYGCPSA-N 0.000 description 2
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 2
- SGEIEGAXKLMUIZ-ZPTIMJQQSA-N (3e)-n-[(2r)-2-hydroxy-3-piperidin-1-ylpropoxy]-1-oxidopyridin-1-ium-3-carboximidoyl chloride Chemical compound C([C@H](O)CN1CCCCC1)O\N=C(\Cl)C1=CC=C[N+]([O-])=C1 SGEIEGAXKLMUIZ-ZPTIMJQQSA-N 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 2
- ASNTZYQMIUCEBV-UHFFFAOYSA-N 2,5-dioxo-1-[6-[3-(pyridin-2-yldisulfanyl)propanoylamino]hexanoyloxy]pyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)CCCCCNC(=O)CCSSC1=CC=CC=N1 ASNTZYQMIUCEBV-UHFFFAOYSA-N 0.000 description 2
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 2
- YFGHCGITMMYXAQ-UHFFFAOYSA-N 2-[(diphenylmethyl)sulfinyl]acetamide Chemical compound C=1C=CC=CC=1C(S(=O)CC(=O)N)C1=CC=CC=C1 YFGHCGITMMYXAQ-UHFFFAOYSA-N 0.000 description 2
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 2
- YSGASDXSLKIKOD-UHFFFAOYSA-N 2-amino-N-(1,2-diphenylpropan-2-yl)acetamide Chemical compound C=1C=CC=CC=1C(C)(NC(=O)CN)CC1=CC=CC=C1 YSGASDXSLKIKOD-UHFFFAOYSA-N 0.000 description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical class OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 description 2
- UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 description 2
- UYNVMODNBIQBMV-UHFFFAOYSA-N 4-[1-hydroxy-2-[4-(phenylmethyl)-1-piperidinyl]propyl]phenol Chemical compound C1CC(CC=2C=CC=CC=2)CCN1C(C)C(O)C1=CC=C(O)C=C1 UYNVMODNBIQBMV-UHFFFAOYSA-N 0.000 description 2
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 2
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 2
- LMBRMGBMWZLWDO-UHFFFAOYSA-N 8-methyl-6,7-dihydro-[1,3]dioxolo[4,5-i][2,3]benzodiazepine Chemical compound C1=NN(C)CCC2=CC=C(OCO3)C3=C21 LMBRMGBMWZLWDO-UHFFFAOYSA-N 0.000 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- 102100020970 ATP-binding cassette sub-family D member 2 Human genes 0.000 description 2
- 206010000117 Abnormal behaviour Diseases 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 2
- 208000018126 Adrenomyeloneuropathy Diseases 0.000 description 2
- 102100028116 Amine oxidase [flavin-containing] B Human genes 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical group N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- 102100026198 Aspartate-tRNA ligase, mitochondrial Human genes 0.000 description 2
- 208000036640 Asperger disease Diseases 0.000 description 2
- 201000006062 Asperger syndrome Diseases 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- 206010003591 Ataxia Diseases 0.000 description 2
- 102000014461 Ataxins Human genes 0.000 description 2
- 108010078286 Ataxins Proteins 0.000 description 2
- 206010003805 Autism Diseases 0.000 description 2
- 208000020706 Autistic disease Diseases 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 240000001546 Byrsonima crassifolia Species 0.000 description 2
- 235000003197 Byrsonima crassifolia Nutrition 0.000 description 2
- 208000010482 CADASIL Diseases 0.000 description 2
- 102000011727 Caspases Human genes 0.000 description 2
- 108010076667 Caspases Proteins 0.000 description 2
- 108091006146 Channels Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 206010048650 Cholinesterase inhibition Diseases 0.000 description 2
- 206010008748 Chorea Diseases 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 208000028006 Corneal injury Diseases 0.000 description 2
- 208000011990 Corticobasal Degeneration Diseases 0.000 description 2
- 108010092160 Dactinomycin Proteins 0.000 description 2
- 206010067889 Dementia with Lewy bodies Diseases 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 238000005698 Diels-Alder reaction Methods 0.000 description 2
- 208000007590 Disorders of Excessive Somnolence Diseases 0.000 description 2
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 208000012661 Dyskinesia Diseases 0.000 description 2
- 206010058314 Dysplasia Diseases 0.000 description 2
- 102100031780 Endonuclease Human genes 0.000 description 2
- 108010042407 Endonucleases Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000283074 Equus asinus Species 0.000 description 2
- 102000003951 Erythropoietin Human genes 0.000 description 2
- 108090000394 Erythropoietin Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 description 2
- 108010044091 Globulins Proteins 0.000 description 2
- 102000006395 Globulins Human genes 0.000 description 2
- 102000018899 Glutamate Receptors Human genes 0.000 description 2
- 108010027915 Glutamate Receptors Proteins 0.000 description 2
- 229940122459 Glutamate antagonist Drugs 0.000 description 2
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 2
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 2
- 101000783774 Homo sapiens ATP-binding cassette sub-family D member 2 Proteins 0.000 description 2
- 101000630206 Homo sapiens Aspartate-tRNA ligase, mitochondrial Proteins 0.000 description 2
- 206010058359 Hypogonadism Diseases 0.000 description 2
- 208000006083 Hypokinesia Diseases 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 239000004201 L-cysteine Substances 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 2
- DUGOZIWVEXMGBE-UHFFFAOYSA-N Methylphenidate Chemical compound C=1C=CC=CC=1C(C(=O)OC)C1CCCCN1 DUGOZIWVEXMGBE-UHFFFAOYSA-N 0.000 description 2
- 108010062431 Monoamine oxidase Proteins 0.000 description 2
- 208000026072 Motor neurone disease Diseases 0.000 description 2
- OUSFTKFNBAZUKL-UHFFFAOYSA-N N-(5-{[(5-tert-butyl-1,3-oxazol-2-yl)methyl]sulfanyl}-1,3-thiazol-2-yl)piperidine-4-carboxamide Chemical compound O1C(C(C)(C)C)=CN=C1CSC(S1)=CN=C1NC(=O)C1CCNCC1 OUSFTKFNBAZUKL-UHFFFAOYSA-N 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- 125000003047 N-acetyl group Chemical group 0.000 description 2
- 229940099433 NMDA receptor antagonist Drugs 0.000 description 2
- 206010029113 Neovascularisation Diseases 0.000 description 2
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 2
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 2
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 2
- 239000000006 Nitroglycerin Substances 0.000 description 2
- 240000007817 Olea europaea Species 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- 206010030348 Open-Angle Glaucoma Diseases 0.000 description 2
- 239000012270 PD-1 inhibitor Substances 0.000 description 2
- 239000012668 PD-1-inhibitor Substances 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 2
- 235000019483 Peanut oil Nutrition 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 239000004264 Petrolatum Substances 0.000 description 2
- 108010004729 Phycoerythrin Proteins 0.000 description 2
- 208000007641 Pinealoma Diseases 0.000 description 2
- 239000004721 Polyphenylene oxide Substances 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 206010037180 Psychiatric symptoms Diseases 0.000 description 2
- 239000013614 RNA sample Substances 0.000 description 2
- 208000006289 Rett Syndrome Diseases 0.000 description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
- 206010041349 Somnolence Diseases 0.000 description 2
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 235000019486 Sunflower oil Nutrition 0.000 description 2
- JACAAXNEHGBPOQ-LLVKDONJSA-N Talampanel Chemical compound C([C@H](N(N=1)C(C)=O)C)C2=CC=3OCOC=3C=C2C=1C1=CC=C(N)C=C1 JACAAXNEHGBPOQ-LLVKDONJSA-N 0.000 description 2
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 2
- 208000030886 Traumatic Brain injury Diseases 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 229930003427 Vitamin E Natural products 0.000 description 2
- 201000004525 Zellweger Syndrome Diseases 0.000 description 2
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 2
- 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 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 208000002552 acute disseminated encephalomyelitis Diseases 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 230000016571 aggressive behavior Effects 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 150000001345 alkine derivatives Chemical class 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000003194 amino acid receptor blocking agent Substances 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 239000004037 angiogenesis inhibitor Substances 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 229940035678 anti-parkinson drug Drugs 0.000 description 2
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 239000002249 anxiolytic agent Substances 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- 238000003782 apoptosis assay Methods 0.000 description 2
- 239000008365 aqueous carrier Substances 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 229950011582 arimoclomol Drugs 0.000 description 2
- 239000003693 atypical antipsychotic agent Substances 0.000 description 2
- 229940127236 atypical antipsychotics Drugs 0.000 description 2
- 230000004900 autophagic degradation Effects 0.000 description 2
- 201000004562 autosomal dominant cerebellar ataxia Diseases 0.000 description 2
- 229940120638 avastin Drugs 0.000 description 2
- 229960004099 azithromycin Drugs 0.000 description 2
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 239000000022 bacteriostatic agent Substances 0.000 description 2
- 229940049706 benzodiazepine Drugs 0.000 description 2
- 150000001557 benzodiazepines Chemical class 0.000 description 2
- 229960000397 bevacizumab Drugs 0.000 description 2
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 2
- 229960000516 bezafibrate Drugs 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000005101 blood-brain tumor barrier Anatomy 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 230000007177 brain activity Effects 0.000 description 2
- 210000000133 brain stem Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229960001058 bupropion Drugs 0.000 description 2
- SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 description 2
- BPKIGYQJPYCAOW-FFJTTWKXSA-I calcium;potassium;disodium;(2s)-2-hydroxypropanoate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].C[C@H](O)C([O-])=O BPKIGYQJPYCAOW-FFJTTWKXSA-I 0.000 description 2
- 229940022399 cancer vaccine Drugs 0.000 description 2
- 238000009566 cancer vaccine Methods 0.000 description 2
- 238000000237 capillary viscometry Methods 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003543 catechol methyltransferase inhibitor Substances 0.000 description 2
- VAAUVRVFOQPIGI-SPQHTLEESA-N ceftriaxone Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C(=O)NN1C VAAUVRVFOQPIGI-SPQHTLEESA-N 0.000 description 2
- 229960004755 ceftriaxone Drugs 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 210000003855 cell nucleus Anatomy 0.000 description 2
- 230000007248 cellular mechanism Effects 0.000 description 2
- 208000016886 cerebral arteriopathy with subcortical infarcts and leukoencephalopathy Diseases 0.000 description 2
- 230000003727 cerebral blood flow Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 239000000812 cholinergic antagonist Substances 0.000 description 2
- 208000012601 choreatic disease Diseases 0.000 description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 229960001653 citalopram Drugs 0.000 description 2
- 229960002626 clarithromycin Drugs 0.000 description 2
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 229960003120 clonazepam Drugs 0.000 description 2
- DGBIGWXXNGSACT-UHFFFAOYSA-N clonazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1Cl DGBIGWXXNGSACT-UHFFFAOYSA-N 0.000 description 2
- 230000006999 cognitive decline Effects 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 229940125758 compound 15 Drugs 0.000 description 2
- 229940127204 compound 29 Drugs 0.000 description 2
- 229940125877 compound 31 Drugs 0.000 description 2
- 229940125807 compound 37 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 235000005687 corn oil Nutrition 0.000 description 2
- 239000002285 corn oil Substances 0.000 description 2
- 230000001054 cortical effect Effects 0.000 description 2
- 239000003246 corticosteroid Substances 0.000 description 2
- 235000012343 cottonseed oil Nutrition 0.000 description 2
- 239000002385 cottonseed oil Substances 0.000 description 2
- 239000007822 coupling agent Substances 0.000 description 2
- 108010086416 cyclo(arginyl-glycyl-aspartyl-phenylalanyl-cysteinyl) Proteins 0.000 description 2
- 229940097362 cyclodextrins Drugs 0.000 description 2
- YPHMISFOHDHNIV-FSZOTQKASA-N cycloheximide Chemical compound C1[C@@H](C)C[C@H](C)C(=O)[C@@H]1[C@H](O)CC1CC(=O)NC(=O)C1 YPHMISFOHDHNIV-FSZOTQKASA-N 0.000 description 2
- 208000031513 cyst Diseases 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 229960000640 dactinomycin Drugs 0.000 description 2
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 2
- 229960000975 daunorubicin Drugs 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 239000000534 dopa decarboxylase inhibitor Substances 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 229940052760 dopamine agonists Drugs 0.000 description 2
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 2
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 229950009041 edaravone Drugs 0.000 description 2
- 239000003792 electrolyte Substances 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 229960003276 erythromycin Drugs 0.000 description 2
- 229940105423 erythropoietin Drugs 0.000 description 2
- 229960004341 escitalopram Drugs 0.000 description 2
- 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 2
- 238000010931 ester hydrolysis Methods 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- WKGXYQFOCVYPAC-UHFFFAOYSA-N felbamate Chemical compound NC(=O)OCC(COC(N)=O)C1=CC=CC=C1 WKGXYQFOCVYPAC-UHFFFAOYSA-N 0.000 description 2
- 229960003472 felbamate Drugs 0.000 description 2
- 235000019688 fish Nutrition 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 239000012737 fresh medium Substances 0.000 description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 229960003711 glyceryl trinitrate Drugs 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000009931 harmful effect Effects 0.000 description 2
- 230000000971 hippocampal effect Effects 0.000 description 2
- 238000000265 homogenisation Methods 0.000 description 2
- 229920001477 hydrophilic polymer Polymers 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 229920006150 hyperbranched polyester Polymers 0.000 description 2
- 230000001969 hypertrophic effect Effects 0.000 description 2
- 230000003483 hypokinetic effect Effects 0.000 description 2
- 230000002631 hypothermal effect Effects 0.000 description 2
- 229960001680 ibuprofen Drugs 0.000 description 2
- 229960003998 ifenprodil Drugs 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000001361 intraarterial administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- 201000010666 keratoconjunctivitis Diseases 0.000 description 2
- PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 2
- 229960001848 lamotrigine Drugs 0.000 description 2
- 238000002350 laparotomy Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 229940091250 magnesium supplement Drugs 0.000 description 2
- 230000005291 magnetic effect Effects 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 229960003987 melatonin Drugs 0.000 description 2
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- 229960001344 methylphenidate Drugs 0.000 description 2
- 238000001531 micro-dissection Methods 0.000 description 2
- 229960001165 modafinil Drugs 0.000 description 2
- 208000005264 motor neuron disease Diseases 0.000 description 2
- 230000002151 myoclonic effect Effects 0.000 description 2
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 2
- 239000003706 n methyl dextro aspartic acid receptor stimulating agent Substances 0.000 description 2
- 239000002086 nanomaterial Substances 0.000 description 2
- 210000001577 neostriatum Anatomy 0.000 description 2
- 230000000626 neurodegenerative effect Effects 0.000 description 2
- 230000002314 neuroinflammatory effect Effects 0.000 description 2
- 230000009251 neurologic dysfunction Effects 0.000 description 2
- 208000015015 neurological dysfunction Diseases 0.000 description 2
- 231100000878 neurological injury Toxicity 0.000 description 2
- 238000011587 new zealand white rabbit Methods 0.000 description 2
- 229960000715 nimodipine Drugs 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 239000002767 noradrenalin uptake inhibitor Substances 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 229960005017 olanzapine Drugs 0.000 description 2
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 150000002895 organic esters Chemical class 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 230000000242 pagocytic effect Effects 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 229960002296 paroxetine Drugs 0.000 description 2
- 229940121655 pd-1 inhibitor Drugs 0.000 description 2
- 239000000312 peanut oil Substances 0.000 description 2
- 210000002824 peroxisome Anatomy 0.000 description 2
- 229940066842 petrolatum Drugs 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000001699 photocatalysis Effects 0.000 description 2
- 229960005095 pioglitazone Drugs 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920000223 polyglycerol Polymers 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000035935 pregnancy Effects 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 230000005522 programmed cell death Effects 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 229960004431 quetiapine Drugs 0.000 description 2
- URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 description 2
- 229950000659 remacemide Drugs 0.000 description 2
- UXIGZRQVLGFTOU-VQXQMPIVSA-N remikiren Chemical compound C([C@H](CS(=O)(=O)C(C)(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC1CCCCC1)[C@@H](O)[C@@H](O)C1CC1)C1=CC=CC=C1 UXIGZRQVLGFTOU-VQXQMPIVSA-N 0.000 description 2
- 230000003989 repetitive behavior Effects 0.000 description 2
- 208000013406 repetitive behavior Diseases 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 229940072169 rilutek Drugs 0.000 description 2
- 229960004181 riluzole Drugs 0.000 description 2
- WVYADZUPLLSGPU-UHFFFAOYSA-N salsalate Chemical compound OC(=O)C1=CC=CC=C1OC(=O)C1=CC=CC=C1O WVYADZUPLLSGPU-UHFFFAOYSA-N 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 description 2
- 229960003946 selegiline Drugs 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 2
- 239000008159 sesame oil Substances 0.000 description 2
- 235000011803 sesame oil Nutrition 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 235000010378 sodium ascorbate Nutrition 0.000 description 2
- 229960005055 sodium ascorbate Drugs 0.000 description 2
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 2
- 239000003195 sodium channel blocking agent Substances 0.000 description 2
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
- 235000012424 soybean oil Nutrition 0.000 description 2
- 208000020431 spinal cord injury Diseases 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 238000011517 stereotactic body radiotherapy Methods 0.000 description 2
- 230000002739 subcortical effect Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 239000002600 sunflower oil Substances 0.000 description 2
- 230000008093 supporting effect Effects 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 231100000057 systemic toxicity Toxicity 0.000 description 2
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 2
- 229950004608 talampanel Drugs 0.000 description 2
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 2
- 229960001278 teniposide Drugs 0.000 description 2
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 2
- 229960005333 tetrabenazine Drugs 0.000 description 2
- 229960003433 thalidomide Drugs 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical class OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 2
- 230000034005 thiol-disulfide exchange Effects 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- 230000009529 traumatic brain injury Effects 0.000 description 2
- 150000003852 triazoles Chemical group 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- ZYTXTXAMMDTYDQ-DGEXFFLYSA-N vamorolone Chemical compound C([C@H]12)CC3=CC(=O)C=C[C@]3(C)C1=CC[C@@]1(C)[C@H]2C[C@@H](C)[C@]1(O)C(=O)CO ZYTXTXAMMDTYDQ-DGEXFFLYSA-N 0.000 description 2
- 210000005166 vasculature Anatomy 0.000 description 2
- 235000013311 vegetables Nutrition 0.000 description 2
- 229960004688 venlafaxine Drugs 0.000 description 2
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 235000019165 vitamin E Nutrition 0.000 description 2
- 229940046009 vitamin E Drugs 0.000 description 2
- 239000011709 vitamin E Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 1
- VYEKJNGRMIAFMH-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-(1-pyridin-2-ylsulfanylethyl)benzoate Chemical compound C=1C=C(C(=O)ON2C(CCC2=O)=O)C=CC=1C(C)SC1=CC=CC=N1 VYEKJNGRMIAFMH-UHFFFAOYSA-N 0.000 description 1
- QYEAAMBIUQLHFQ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-[3-(pyridin-2-yldisulfanyl)propanoylamino]hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCNC(=O)CCSSC1=CC=CC=N1 QYEAAMBIUQLHFQ-UHFFFAOYSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- ABXYOVCSAGTJAC-JGWLITMVSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanethial Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=S ABXYOVCSAGTJAC-JGWLITMVSA-N 0.000 description 1
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 description 1
- AEGSIYIIMVBZQU-CIUDSAMLSA-N (3s)-3-[[2-[[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-4-[[(1r)-1-carboxy-2-sulfanylethyl]amino]-4-oxobutanoic acid Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CS)C(O)=O AEGSIYIIMVBZQU-CIUDSAMLSA-N 0.000 description 1
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 1
- YJGVMLPVUAXIQN-LGWHJFRWSA-N (5s,5ar,8ar,9r)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5h-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-LGWHJFRWSA-N 0.000 description 1
- FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 description 1
- KQJSQWZMSAGSHN-UHFFFAOYSA-N (9beta,13alpha,14beta,20alpha)-3-hydroxy-9,13-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid Natural products CC12CCC3(C)C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C2=CC=C2C1=CC(=O)C(O)=C2C KQJSQWZMSAGSHN-UHFFFAOYSA-N 0.000 description 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-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
- XUBOMFCQGDBHNK-JTQLQIEISA-N (S)-gatifloxacin Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCN[C@@H](C)C1 XUBOMFCQGDBHNK-JTQLQIEISA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- SDTADDXWFMZCEW-UHFFFAOYSA-N 1-(pyridin-2-yldisulfanyl)ethanol Chemical compound CC(O)SSC1=CC=CC=N1 SDTADDXWFMZCEW-UHFFFAOYSA-N 0.000 description 1
- PEAFNIBKNAERKN-UHFFFAOYSA-N 1-[1-(2,5-dioxopyrrol-1-yl)-1-hydroxy-2-(2-hydroxyethoxy)ethyl]pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1C(O)(COCCO)N1C(=O)C=CC1=O PEAFNIBKNAERKN-UHFFFAOYSA-N 0.000 description 1
- KXBULHLXXUTQJU-UHFFFAOYSA-N 1-[1-(2,5-dioxopyrrol-1-yl)-1-hydroxy-2-[2-(2-hydroxyethoxy)ethoxy]ethyl]pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1C(O)(COCCOCCO)N1C(=O)C=CC1=O KXBULHLXXUTQJU-UHFFFAOYSA-N 0.000 description 1
- RVRLFABOQXZUJX-UHFFFAOYSA-N 1-[1-(2,5-dioxopyrrol-1-yl)ethyl]pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1C(C)N1C(=O)C=CC1=O RVRLFABOQXZUJX-UHFFFAOYSA-N 0.000 description 1
- AASYSXRGODIQGY-UHFFFAOYSA-N 1-[1-(2,5-dioxopyrrol-1-yl)hexyl]pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1C(CCCCC)N1C(=O)C=CC1=O AASYSXRGODIQGY-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000004009 13C{1H}-NMR spectroscopy Methods 0.000 description 1
- 206010068533 18q minus syndrome Diseases 0.000 description 1
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 1
- 150000003923 2,5-pyrrolediones Chemical class 0.000 description 1
- WNYJVAMZRBTOPE-YVSFHVDLSA-N 2-[(2s,5r,8r,11s)-5-benzyl-11-[3-(diaminomethylideneamino)propyl]-3,6,9,12,15-pentaoxo-8-(sulfanylmethyl)-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid Chemical compound N1C(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CS)NC(=O)[C@H]1CC1=CC=CC=C1 WNYJVAMZRBTOPE-YVSFHVDLSA-N 0.000 description 1
- WZPBZJONDBGPKJ-VEHQQRBSSA-L 2-[(z)-[1-(2-amino-1,3-thiazol-4-yl)-2-[[(2s,3s)-2-methyl-4-oxo-1-sulfonatoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxy-2-methylpropanoate Chemical compound O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C([O-])=O)\C1=CSC(N)=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-L 0.000 description 1
- PTOJCKLTCKYNFG-UHFFFAOYSA-N 2-[2-(2-azidoethoxy)ethoxy]ethyl 4-methylbenzenesulfonate Chemical compound CC1=CC=C(S(=O)(=O)OCCOCCOCCN=[N+]=[N-])C=C1 PTOJCKLTCKYNFG-UHFFFAOYSA-N 0.000 description 1
- YHELUJCERLGVBD-UHFFFAOYSA-N 2-[2-(4-chlorophenyl)-1-phenyl-6,7-dihydro-5h-pyrrolizin-3-yl]acetic acid Chemical compound C=12CCCN2C(CC(=O)O)=C(C=2C=CC(Cl)=CC=2)C=1C1=CC=CC=C1 YHELUJCERLGVBD-UHFFFAOYSA-N 0.000 description 1
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 1
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 1
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- DJBRKGZFUXKLKO-UHFFFAOYSA-N 3-(pyridin-2-yldisulfanyl)propanoic acid Chemical compound OC(=O)CCSSC1=CC=CC=N1 DJBRKGZFUXKLKO-UHFFFAOYSA-N 0.000 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 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
- OBKXEAXTFZPCHS-UHFFFAOYSA-M 4-phenylbutyrate Chemical compound [O-]C(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-M 0.000 description 1
- DTRIDVOOPAQEEL-UHFFFAOYSA-N 4-sulfanylbutanoic acid Chemical class OC(=O)CCCS DTRIDVOOPAQEEL-UHFFFAOYSA-N 0.000 description 1
- GCIZMJUHGHGRNW-UHFFFAOYSA-N 5-sulfanylpentanoic acid Chemical class OC(=O)CCCCS GCIZMJUHGHGRNW-UHFFFAOYSA-N 0.000 description 1
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 1
- CMNQZZPAVNBESS-UHFFFAOYSA-N 6-sulfanylhexanoic acid Chemical class OC(=O)CCCCCS CMNQZZPAVNBESS-UHFFFAOYSA-N 0.000 description 1
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 1
- WLCZTRVUXYALDD-IBGZPJMESA-N 7-[[(2s)-2,6-bis(2-methoxyethoxycarbonylamino)hexanoyl]amino]heptoxy-methylphosphinic acid Chemical compound COCCOC(=O)NCCCC[C@H](NC(=O)OCCOC)C(=O)NCCCCCCCOP(C)(O)=O WLCZTRVUXYALDD-IBGZPJMESA-N 0.000 description 1
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 description 1
- 102100033391 ATP-dependent RNA helicase DDX3X Human genes 0.000 description 1
- 206010058040 Abdominal sepsis Diseases 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 208000032194 Acute haemorrhagic leukoencephalitis Diseases 0.000 description 1
- 208000034014 Adult-onset autosomal dominant leukodystrophy Diseases 0.000 description 1
- 238000006596 Alder-ene reaction Methods 0.000 description 1
- 208000011403 Alexander disease Diseases 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 102100040121 Allograft inflammatory factor 1 Human genes 0.000 description 1
- 208000023434 Alpers-Huttenlocher syndrome Diseases 0.000 description 1
- 208000031277 Amaurotic familial idiocy Diseases 0.000 description 1
- 208000033861 Amoebic keratitis Diseases 0.000 description 1
- 206010002027 Amyotrophy Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 201000002862 Angle-Closure Glaucoma Diseases 0.000 description 1
- WZPBZJONDBGPKJ-UHFFFAOYSA-N Antibiotic SQ 26917 Natural products O=C1N(S(O)(=O)=O)C(C)C1NC(=O)C(=NOC(C)(C)C(O)=O)C1=CSC(N)=N1 WZPBZJONDBGPKJ-UHFFFAOYSA-N 0.000 description 1
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical class NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 1
- CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 1
- 125000006847 BOC protecting group Chemical group 0.000 description 1
- KPYSYYIEGFHWSV-UHFFFAOYSA-N Baclofen Chemical compound OC(=O)CC(CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-UHFFFAOYSA-N 0.000 description 1
- SPFYMRJSYKOXGV-UHFFFAOYSA-N Baytril Chemical compound C1CN(CC)CCN1C(C(=C1)F)=CC2=C1C(=O)C(C(O)=O)=CN2C1CC1 SPFYMRJSYKOXGV-UHFFFAOYSA-N 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 206010006143 Brain stem glioma Diseases 0.000 description 1
- DPUOLQHDNGRHBS-UHFFFAOYSA-N Brassidinsaeure Natural products CCCCCCCCC=CCCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 208000022526 Canavan disease Diseases 0.000 description 1
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- AQKDBFWJOPNOKZ-UHFFFAOYSA-N Celastrol Natural products CC12CCC3(C)C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C2=CC=C2C1=CC(=O)C(=O)C2C AQKDBFWJOPNOKZ-UHFFFAOYSA-N 0.000 description 1
- 206010008027 Cerebellar atrophy Diseases 0.000 description 1
- 206010053684 Cerebrohepatorenal syndrome Diseases 0.000 description 1
- 208000027104 Chemotherapy-Related Cognitive Impairment Diseases 0.000 description 1
- 201000009047 Chordoma Diseases 0.000 description 1
- 208000002691 Choroiditis Diseases 0.000 description 1
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 1
- 206010009346 Clonus Diseases 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 108010078777 Colistin Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 206010051625 Conjunctival hyperaemia Diseases 0.000 description 1
- 206010011013 Corneal erosion Diseases 0.000 description 1
- 206010055665 Corneal neovascularisation Diseases 0.000 description 1
- 206010011039 Corneal perforation Diseases 0.000 description 1
- 206010054760 Corneal thinning Diseases 0.000 description 1
- 208000009798 Craniopharyngioma Diseases 0.000 description 1
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- 108010069514 Cyclic Peptides Proteins 0.000 description 1
- 102000001189 Cyclic Peptides Human genes 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 208000035976 Developmental Disabilities Diseases 0.000 description 1
- 208000004986 Diffuse Cerebral Sclerosis of Schilder Diseases 0.000 description 1
- KMSNYNIWEORQDJ-UHFFFAOYSA-N Dihydro-2(3H)-thiophenone Chemical class O=C1CCCS1 KMSNYNIWEORQDJ-UHFFFAOYSA-N 0.000 description 1
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical class OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000037487 Endotoxemia Diseases 0.000 description 1
- 206010014967 Ependymoma Diseases 0.000 description 1
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- URXZXNYJPAJJOQ-UHFFFAOYSA-N Erucic acid Natural products CCCCCCC=CCCCCCCCCCCCC(O)=O URXZXNYJPAJJOQ-UHFFFAOYSA-N 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 206010015911 Eye burns Diseases 0.000 description 1
- 208000026097 Factitious disease Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 208000024412 Friedreich ataxia Diseases 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- 201000001925 Fuchs' endothelial dystrophy Diseases 0.000 description 1
- 208000014260 Fungal keratitis Diseases 0.000 description 1
- 208000003736 Gerstmann-Straussler-Scheinker Disease Diseases 0.000 description 1
- 206010072075 Gerstmann-Straussler-Scheinker syndrome Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 206010018341 Gliosis Diseases 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 238000006595 Griess deamination reaction Methods 0.000 description 1
- 101000870662 Homo sapiens ATP-dependent RNA helicase DDX3X Proteins 0.000 description 1
- 101000890626 Homo sapiens Allograft inflammatory factor 1 Proteins 0.000 description 1
- 101001134216 Homo sapiens Macrophage scavenger receptor types I and II Proteins 0.000 description 1
- 101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 description 1
- 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 description 1
- 101000728860 Homo sapiens Ribonuclease T2 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 238000006736 Huisgen cycloaddition reaction Methods 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- 206010055001 Hypodontia Diseases 0.000 description 1
- 208000018175 Hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome Diseases 0.000 description 1
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000013691 Interleukin-17 Human genes 0.000 description 1
- 108050003558 Interleukin-17 Proteins 0.000 description 1
- 206010061252 Intraocular melanoma Diseases 0.000 description 1
- 206010022941 Iridocyclitis Diseases 0.000 description 1
- 208000006264 Korsakoff syndrome Diseases 0.000 description 1
- 235000013878 L-cysteine Nutrition 0.000 description 1
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 208000004552 Lacunar Stroke Diseases 0.000 description 1
- 208000025121 Leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome Diseases 0.000 description 1
- GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 description 1
- 208000035752 Live birth Diseases 0.000 description 1
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 1
- 201000002961 MASA syndrome Diseases 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 102100034184 Macrophage scavenger receptor types I and II Human genes 0.000 description 1
- 208000001344 Macular Edema Diseases 0.000 description 1
- 206010025415 Macular oedema Diseases 0.000 description 1
- 206010025421 Macule Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- SBDNJUWAMKYJOX-UHFFFAOYSA-N Meclofenamic Acid Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C(O)=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-N 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 206010065062 Meibomian gland dysfunction Diseases 0.000 description 1
- 229920000877 Melamine resin Polymers 0.000 description 1
- ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 description 1
- XOGTZOOQQBDUSI-UHFFFAOYSA-M Mesna Chemical compound [Na+].[O-]S(=O)(=O)CCS XOGTZOOQQBDUSI-UHFFFAOYSA-M 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- 238000006957 Michael reaction Methods 0.000 description 1
- 108700011259 MicroRNAs Proteins 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- 102000047918 Myelin Basic Human genes 0.000 description 1
- 101710107068 Myelin basic protein Proteins 0.000 description 1
- 206010028570 Myelopathy Diseases 0.000 description 1
- 208000002033 Myoclonus Diseases 0.000 description 1
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
- 210000005156 Müller Glia Anatomy 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 206010028923 Neonatal asphyxia Diseases 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- 208000002537 Neuronal Ceroid-Lipofuscinoses Diseases 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- JZFPYUNJRRFVQU-UHFFFAOYSA-N Niflumic acid Chemical compound OC(=O)C1=CC=CN=C1NC1=CC=CC(C(F)(F)F)=C1 JZFPYUNJRRFVQU-UHFFFAOYSA-N 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 201000010133 Oligodendroglioma Diseases 0.000 description 1
- 206010031127 Orthostatic hypotension Diseases 0.000 description 1
- 101800000989 Oxytocin Proteins 0.000 description 1
- 238000010222 PCR analysis Methods 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 208000017493 Pelizaeus-Merzbacher disease Diseases 0.000 description 1
- 206010035015 Pigmentary glaucoma Diseases 0.000 description 1
- 206010050487 Pinealoblastoma Diseases 0.000 description 1
- 208000007913 Pituitary Neoplasms Diseases 0.000 description 1
- 206010035138 Placental insufficiency Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 208000003971 Posterior uveitis Diseases 0.000 description 1
- 208000005107 Premature Birth Diseases 0.000 description 1
- 208000024777 Prion disease Diseases 0.000 description 1
- 102100024028 Progonadoliberin-1 Human genes 0.000 description 1
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 1
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 208000008425 Protein deficiency Diseases 0.000 description 1
- 206010052276 Pseudodementia Diseases 0.000 description 1
- 208000005587 Refsum Disease Diseases 0.000 description 1
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010057430 Retinal injury Diseases 0.000 description 1
- 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
- 206010038926 Retinopathy hypertensive Diseases 0.000 description 1
- 206010038933 Retinopathy of prematurity Diseases 0.000 description 1
- 102100029683 Ribonuclease T2 Human genes 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 229930182475 S-glycoside Natural products 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 description 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
- WFWLQNSHRPWKFK-UHFFFAOYSA-N Tegafur Chemical compound O=C1NC(=O)C(F)=CN1C1OCCC1 WFWLQNSHRPWKFK-UHFFFAOYSA-N 0.000 description 1
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 1
- UWHCKJMYHZGTIT-UHFFFAOYSA-N Tetraethylene glycol, Natural products OCCOCCOCCOCCO UWHCKJMYHZGTIT-UHFFFAOYSA-N 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- IVTVGDXNLFLDRM-HNNXBMFYSA-N Tomudex Chemical compound C=1C=C2NC(C)=NC(=O)C2=CC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)S1 IVTVGDXNLFLDRM-HNNXBMFYSA-N 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 201000005485 Toxoplasmosis Diseases 0.000 description 1
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- YCPOZVAOBBQLRI-WDSKDSINSA-N Treosulfan Chemical compound CS(=O)(=O)OC[C@H](O)[C@@H](O)COS(C)(=O)=O YCPOZVAOBBQLRI-WDSKDSINSA-N 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 206010046793 Uterine inflammation Diseases 0.000 description 1
- 201000005969 Uveal melanoma Diseases 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 201000008485 Wernicke-Korsakoff syndrome Diseases 0.000 description 1
- 208000016807 X-linked intellectual disability-macrocephaly-macroorchidism syndrome Diseases 0.000 description 1
- 208000036813 Zellweger spectrum disease Diseases 0.000 description 1
- 229940056213 abilify Drugs 0.000 description 1
- 238000005299 abrasion Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 208000004064 acoustic neuroma Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 208000030597 adult Refsum disease Diseases 0.000 description 1
- 201000001452 adult-onset autosomal dominant demyelinating leukodystrophy Diseases 0.000 description 1
- 201000008445 adult-onset leukoencephalopathy with axonal spheroids and pigmented glia Diseases 0.000 description 1
- 238000012382 advanced drug delivery Methods 0.000 description 1
- 229960002833 aflibercept Drugs 0.000 description 1
- 108010081667 aflibercept Proteins 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 125000002009 alkene group Chemical group 0.000 description 1
- 150000001336 alkenes Chemical group 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 238000005937 allylation reaction Methods 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 1
- 229960001220 amsacrine Drugs 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 206010002583 anodontia Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 201000004612 anterior uveitis Diseases 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 229940124650 anti-cancer therapies Drugs 0.000 description 1
- 230000000781 anti-lymphocytic effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000001494 anti-thymocyte effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 239000012223 aqueous fraction Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 1
- 108010006195 arginyl-glycyl-aspartyl-cysteine Proteins 0.000 description 1
- 239000003886 aromatase inhibitor Substances 0.000 description 1
- 229940046844 aromatase inhibitors Drugs 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 208000037875 astrocytosis Diseases 0.000 description 1
- 230000007341 astrogliosis Effects 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 208000029560 autism spectrum disease Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 201000004982 autoimmune uveitis Diseases 0.000 description 1
- 230000003376 axonal effect Effects 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 238000010461 azide-alkyne cycloaddition reaction Methods 0.000 description 1
- 229960003644 aztreonam Drugs 0.000 description 1
- 201000007917 background diabetic retinopathy Diseases 0.000 description 1
- 229960000794 baclofen Drugs 0.000 description 1
- 210000004227 basal ganglia Anatomy 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 238000009227 behaviour therapy Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WPIHMWBQRSAMDE-YCZTVTEBSA-N beta-D-galactosyl-(1->4)-beta-D-galactosyl-N-(pentacosanoyl)sphingosine Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@@H](CO[C@@H]1O[C@H](CO)[C@H](O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@H]1O)[C@H](O)\C=C\CCCCCCCCCCCCC WPIHMWBQRSAMDE-YCZTVTEBSA-N 0.000 description 1
- 239000000560 biocompatible material Substances 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 208000010217 blepharitis Diseases 0.000 description 1
- 244000078885 bloodborne pathogen Species 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 210000001775 bruch membrane Anatomy 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000005587 carbonate group Chemical group 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- QYIYFLOTGYLRGG-GPCCPHFNSA-N cefaclor Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3C(=C(Cl)CS[C@@H]32)C(O)=O)=O)N)=CC=CC=C1 QYIYFLOTGYLRGG-GPCCPHFNSA-N 0.000 description 1
- 229960005361 cefaclor Drugs 0.000 description 1
- WYUSVOMTXWRGEK-HBWVYFAYSA-N cefpodoxime Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC)C(O)=O)C(=O)C(=N/OC)\C1=CSC(N)=N1 WYUSVOMTXWRGEK-HBWVYFAYSA-N 0.000 description 1
- 229960005090 cefpodoxime Drugs 0.000 description 1
- 229960001668 cefuroxime Drugs 0.000 description 1
- JFPVXVDWJQMJEE-IZRZKJBUSA-N cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 JFPVXVDWJQMJEE-IZRZKJBUSA-N 0.000 description 1
- KQJSQWZMSAGSHN-JJWQIEBTSA-N celastrol Chemical compound C([C@H]1[C@]2(C)CC[C@@]34C)[C@](C)(C(O)=O)CC[C@]1(C)CC[C@]2(C)C4=CC=C1C3=CC(=O)C(O)=C1C KQJSQWZMSAGSHN-JJWQIEBTSA-N 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 238000003570 cell viability assay Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 description 1
- 229940106164 cephalexin Drugs 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- 230000006720 chronic neuroinflammation Effects 0.000 description 1
- 208000007118 chronic progressive multiple sclerosis Diseases 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 229960002436 cladribine Drugs 0.000 description 1
- YNNUSGIPVFPVBX-NHCUHLMSSA-N clemastine Chemical compound CN1CCC[C@@H]1CCO[C@@](C)(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 YNNUSGIPVFPVBX-NHCUHLMSSA-N 0.000 description 1
- 229960002881 clemastine Drugs 0.000 description 1
- 208000035850 clinical syndrome Diseases 0.000 description 1
- WDDPHFBMKLOVOX-AYQXTPAHSA-N clofarabine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1F WDDPHFBMKLOVOX-AYQXTPAHSA-N 0.000 description 1
- 229960000928 clofarabine Drugs 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 229960003346 colistin Drugs 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 238000001218 confocal laser scanning microscopy Methods 0.000 description 1
- 229940039231 contrast media Drugs 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- JZCCFEFSEZPSOG-UHFFFAOYSA-L copper(II) sulfate pentahydrate Chemical compound O.O.O.O.O.[Cu+2].[O-]S([O-])(=O)=O JZCCFEFSEZPSOG-UHFFFAOYSA-L 0.000 description 1
- 206010011005 corneal dystrophy Diseases 0.000 description 1
- 201000000159 corneal neovascularization Diseases 0.000 description 1
- 201000007717 corneal ulcer Diseases 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 229940111134 coxibs Drugs 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- 230000000254 damaging effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 230000003413 degradative effect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 229940029030 dendritic cell vaccine Drugs 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- 229960001193 diclofenac sodium Drugs 0.000 description 1
- 230000009274 differential gene expression Effects 0.000 description 1
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 1
- 229960000616 diflunisal Drugs 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000012678 divergent method Methods 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000011143 downstream manufacturing Methods 0.000 description 1
- 229960003722 doxycycline Drugs 0.000 description 1
- 229960001850 droxicam Drugs 0.000 description 1
- OEHFRZLKGRKFAS-UHFFFAOYSA-N droxicam Chemical compound C12=CC=CC=C2S(=O)(=O)N(C)C(C2=O)=C1OC(=O)N2C1=CC=CC=N1 OEHFRZLKGRKFAS-UHFFFAOYSA-N 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 208000011325 dry age related macular degeneration Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 206010014801 endophthalmitis Diseases 0.000 description 1
- 229960000740 enrofloxacin Drugs 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- DPUOLQHDNGRHBS-KTKRTIGZSA-N erucic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-KTKRTIGZSA-N 0.000 description 1
- 125000003916 ethylene diamine group Chemical group 0.000 description 1
- 229960005293 etodolac Drugs 0.000 description 1
- XFBVBWWRPKNWHW-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=N[C]3C(CC)=CC=CC3=C21 XFBVBWWRPKNWHW-UHFFFAOYSA-N 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 description 1
- 229960000752 etoposide phosphate Drugs 0.000 description 1
- 229960004945 etoricoxib Drugs 0.000 description 1
- MNJVRJDLRVPLFE-UHFFFAOYSA-N etoricoxib Chemical compound C1=NC(C)=CC=C1C1=NC=C(Cl)C=C1C1=CC=C(S(C)(=O)=O)C=C1 MNJVRJDLRVPLFE-UHFFFAOYSA-N 0.000 description 1
- 239000004060 excitotoxin Substances 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 210000000887 face Anatomy 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229960001419 fenoprofen Drugs 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- FULAPETWGIGNMT-UHFFFAOYSA-N firocoxib Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OCC1CC1 FULAPETWGIGNMT-UHFFFAOYSA-N 0.000 description 1
- 229960002524 firocoxib Drugs 0.000 description 1
- 229960000390 fludarabine Drugs 0.000 description 1
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 1
- LPEPZBJOKDYZAD-UHFFFAOYSA-N flufenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 LPEPZBJOKDYZAD-UHFFFAOYSA-N 0.000 description 1
- 229960004369 flufenamic acid Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229960001347 fluocinolone acetonide Drugs 0.000 description 1
- FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 description 1
- 229940124307 fluoroquinolone Drugs 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 229960002464 fluoxetine Drugs 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 1
- 235000008191 folinic acid Nutrition 0.000 description 1
- 239000011672 folinic acid Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 239000003574 free electron Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- OBKXEAXTFZPCHS-UHFFFAOYSA-N gamma-phenylbutyric acid Natural products OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229960003923 gatifloxacin Drugs 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- 208000002409 gliosarcoma Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 125000003827 glycol group Chemical group 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 230000002414 glycolytic effect Effects 0.000 description 1
- 150000002344 gold compounds Chemical class 0.000 description 1
- XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 1
- 210000004884 grey matter Anatomy 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 125000004404 heteroalkyl group Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 238000010842 high-capacity cDNA reverse transcription kit Methods 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 102000048362 human PDCD1 Human genes 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 208000003906 hydrocephalus Diseases 0.000 description 1
- JUMYIBMBTDDLNG-OJERSXHUSA-N hydron;methyl (2r)-2-phenyl-2-[(2r)-piperidin-2-yl]acetate;chloride Chemical compound Cl.C([C@@H]1[C@H](C(=O)OC)C=2C=CC=CC=2)CCCN1 JUMYIBMBTDDLNG-OJERSXHUSA-N 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 229960001330 hydroxycarbamide Drugs 0.000 description 1
- 201000001948 hypertensive retinopathy Diseases 0.000 description 1
- 230000005213 hypodontia Effects 0.000 description 1
- 201000000770 hypomyelinating leukodystrophy 6 Diseases 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 210000004713 immature microglia Anatomy 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000007124 immune defense Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000002650 immunosuppressive therapy Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000005414 inactive ingredient Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000008798 inflammatory stress Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 108091005434 innate immune receptors Proteins 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 229950002252 isoxicam Drugs 0.000 description 1
- YYUAYBYLJSNDCX-UHFFFAOYSA-N isoxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC=1C=C(C)ON=1 YYUAYBYLJSNDCX-UHFFFAOYSA-N 0.000 description 1
- 208000017476 juvenile neuronal ceroid lipofuscinosis Diseases 0.000 description 1
- 206010023365 keratopathy Diseases 0.000 description 1
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
- 229960000991 ketoprofen Drugs 0.000 description 1
- 229960004752 ketorolac Drugs 0.000 description 1
- OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229960001691 leucovorin Drugs 0.000 description 1
- 229960003376 levofloxacin Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 229960002247 lomustine Drugs 0.000 description 1
- OXROWJKCGCOJDO-JLHYYAGUSA-N lornoxicam Chemical compound O=C1C=2SC(Cl)=CC=2S(=O)(=O)N(C)\C1=C(\O)NC1=CC=CC=N1 OXROWJKCGCOJDO-JLHYYAGUSA-N 0.000 description 1
- 229960002202 lornoxicam Drugs 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 229960002373 loxoprofen Drugs 0.000 description 1
- BAZQYVYVKYOAGO-UHFFFAOYSA-M loxoprofen sodium hydrate Chemical compound O.O.[Na+].C1=CC(C(C([O-])=O)C)=CC=C1CC1C(=O)CCC1 BAZQYVYVKYOAGO-UHFFFAOYSA-M 0.000 description 1
- 229940076783 lucentis Drugs 0.000 description 1
- 229960000994 lumiracoxib Drugs 0.000 description 1
- KHPKQFYUPIUARC-UHFFFAOYSA-N lumiracoxib Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=CC=C1Cl KHPKQFYUPIUARC-UHFFFAOYSA-N 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 201000010230 macular retinal edema Diseases 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000010297 mechanical methods and process Methods 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- 229960003803 meclofenamic acid Drugs 0.000 description 1
- 229960003464 mefenamic acid Drugs 0.000 description 1
- HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 description 1
- 208000002839 megalencephalic leukoencephalopathy with subcortical cysts Diseases 0.000 description 1
- JDSHMPZPIAZGSV-UHFFFAOYSA-N melamine Chemical compound NC1=NC(N)=NC(N)=N1 JDSHMPZPIAZGSV-UHFFFAOYSA-N 0.000 description 1
- 229960001929 meloxicam Drugs 0.000 description 1
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
- 229960001924 melphalan Drugs 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 230000008897 memory decline Effects 0.000 description 1
- 230000006386 memory function Effects 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- 229960001810 meprednisone Drugs 0.000 description 1
- PIDANAQULIKBQS-RNUIGHNZSA-N meprednisone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)CC2=O PIDANAQULIKBQS-RNUIGHNZSA-N 0.000 description 1
- 229960003151 mercaptamine Drugs 0.000 description 1
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- 229960004635 mesna Drugs 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 229960004584 methylprednisolone Drugs 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 208000027061 mild cognitive impairment Diseases 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 201000011540 mitochondrial DNA depletion syndrome 4a Diseases 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- 210000003007 myelin sheath Anatomy 0.000 description 1
- HXJGFDIZSMWOGY-UHFFFAOYSA-N n-(2-azaniumylethyl)prop-2-enimidate Chemical compound NCCNC(=O)C=C HXJGFDIZSMWOGY-UHFFFAOYSA-N 0.000 description 1
- JORAUNFTUVJTNG-BSTBCYLQSA-N n-[(2s)-4-amino-1-[[(2s,3r)-1-[[(2s)-4-amino-1-oxo-1-[[(3s,6s,9s,12s,15r,18s,21s)-6,9,18-tris(2-aminoethyl)-3-[(1r)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-h Chemical compound CC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O.CCC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O JORAUNFTUVJTNG-BSTBCYLQSA-N 0.000 description 1
- 229960004270 nabumetone Drugs 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 208000007538 neurilemmoma Diseases 0.000 description 1
- 201000007601 neurodegeneration with brain iron accumulation Diseases 0.000 description 1
- 230000007472 neurodevelopment Effects 0.000 description 1
- 230000001123 neurodevelopmental effect Effects 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 201000007607 neuronal ceroid lipofuscinosis 3 Diseases 0.000 description 1
- 230000007171 neuropathology Effects 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 229960000916 niflumic acid Drugs 0.000 description 1
- 229960000965 nimesulide Drugs 0.000 description 1
- HYWYRSMBCFDLJT-UHFFFAOYSA-N nimesulide Chemical compound CS(=O)(=O)NC1=CC=C([N+]([O-])=O)C=C1OC1=CC=CC=C1 HYWYRSMBCFDLJT-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 229960003301 nivolumab Drugs 0.000 description 1
- 210000004967 non-hematopoietic stem cell Anatomy 0.000 description 1
- 231100000065 noncytotoxic Toxicity 0.000 description 1
- 230000002020 noncytotoxic effect Effects 0.000 description 1
- 229960001180 norfloxacin Drugs 0.000 description 1
- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 201000002575 ocular melanoma Diseases 0.000 description 1
- 229960001699 ofloxacin Drugs 0.000 description 1
- 210000000956 olfactory bulb Anatomy 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- 229960002739 oxaprozin Drugs 0.000 description 1
- OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 description 1
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 description 1
- 201000007407 panuveitis Diseases 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 229960004662 parecoxib Drugs 0.000 description 1
- TZRHLKRLEZJVIJ-UHFFFAOYSA-N parecoxib Chemical compound C1=CC(S(=O)(=O)NC(=O)CC)=CC=C1C1=C(C)ON=C1C1=CC=CC=C1 TZRHLKRLEZJVIJ-UHFFFAOYSA-N 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000032696 parturition Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007331 pathological accumulation Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 230000008289 pathophysiological mechanism Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940005014 pegaptanib sodium Drugs 0.000 description 1
- 229960002621 pembrolizumab Drugs 0.000 description 1
- 229960005079 pemetrexed Drugs 0.000 description 1
- QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 description 1
- 229960002340 pentostatin Drugs 0.000 description 1
- FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 201000005936 periventricular leukomalacia Diseases 0.000 description 1
- 229950009215 phenylbutanoic acid Drugs 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 208000024724 pineal body neoplasm Diseases 0.000 description 1
- 201000004123 pineal gland cancer Diseases 0.000 description 1
- 201000003113 pineoblastoma Diseases 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- 229940030215 pitocin Drugs 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- XDJYMJULXQKGMM-UHFFFAOYSA-N polymyxin E1 Natural products CCC(C)CCCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCN)NC1=O XDJYMJULXQKGMM-UHFFFAOYSA-N 0.000 description 1
- KNIWPHSUTGNZST-UHFFFAOYSA-N polymyxin E2 Natural products CC(C)CCCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCN)NC1=O KNIWPHSUTGNZST-UHFFFAOYSA-N 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 208000014670 posterior cortical atrophy Diseases 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 208000016800 primary central nervous system lymphoma Diseases 0.000 description 1
- 208000001282 primary progressive aphasia Diseases 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
- 229960000624 procarbazine Drugs 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 206010036807 progressive multifocal leukoencephalopathy Diseases 0.000 description 1
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 1
- 201000007914 proliferative diabetic retinopathy Diseases 0.000 description 1
- DXGIRFAFSFKYCF-UHFFFAOYSA-N propanehydrazide Chemical compound CCC(=O)NN DXGIRFAFSFKYCF-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000004983 proton decoupled 13C NMR spectroscopy Methods 0.000 description 1
- 229940034080 provenge Drugs 0.000 description 1
- 229950000033 proxetil Drugs 0.000 description 1
- 238000013138 pruning Methods 0.000 description 1
- 229960004432 raltitrexed Drugs 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000001846 repelling effect Effects 0.000 description 1
- 235000021283 resveratrol Nutrition 0.000 description 1
- 229940016667 resveratrol Drugs 0.000 description 1
- 210000000844 retinal pigment epithelial cell Anatomy 0.000 description 1
- 239000003161 ribonuclease inhibitor Substances 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 1
- 229940099204 ritalin Drugs 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 229960000953 salsalate Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 190014017285 satraplatin Chemical compound 0.000 description 1
- 229960005399 satraplatin Drugs 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000010845 search algorithm Methods 0.000 description 1
- 150000003334 secondary amides Chemical class 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- PCMORTLOPMLEFB-ONEGZZNKSA-N sinapic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC(OC)=C1O PCMORTLOPMLEFB-ONEGZZNKSA-N 0.000 description 1
- PCMORTLOPMLEFB-UHFFFAOYSA-N sinapinic acid Natural products COC1=CC(C=CC(O)=O)=CC(OC)=C1O PCMORTLOPMLEFB-UHFFFAOYSA-N 0.000 description 1
- 229960000714 sipuleucel-t Drugs 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
- 230000007847 structural defect Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 229960004964 temozolomide Drugs 0.000 description 1
- 229960002871 tenoxicam Drugs 0.000 description 1
- LZNWYQJJBLGYLT-UHFFFAOYSA-N tenoxicam Chemical compound OC=1C=2SC=CC=2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 LZNWYQJJBLGYLT-UHFFFAOYSA-N 0.000 description 1
- GSJJCZSHYJNRPN-UHFFFAOYSA-N tert-butyl n-(2-sulfanylethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCS GSJJCZSHYJNRPN-UHFFFAOYSA-N 0.000 description 1
- 150000003511 tertiary amides Chemical class 0.000 description 1
- 229940072172 tetracycline antibiotic Drugs 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 125000000101 thioether group Chemical group 0.000 description 1
- 150000003569 thioglycosides Chemical class 0.000 description 1
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical compound [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 description 1
- NBOMNTLFRHMDEZ-UHFFFAOYSA-N thiosalicylic acid Chemical group OC(=O)C1=CC=CC=C1S NBOMNTLFRHMDEZ-UHFFFAOYSA-N 0.000 description 1
- 229940103494 thiosalicylic acid Drugs 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- 239000005495 thyroid hormone Substances 0.000 description 1
- 229940036555 thyroid hormone Drugs 0.000 description 1
- 229960003087 tioguanine Drugs 0.000 description 1
- MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 description 1
- 230000030968 tissue homeostasis Effects 0.000 description 1
- 229960000707 tobramycin Drugs 0.000 description 1
- NLVFBUXFDBBNBW-PBSUHMDJSA-N tobramycin Chemical compound N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N NLVFBUXFDBBNBW-PBSUHMDJSA-N 0.000 description 1
- YEZNLOUZAIOMLT-UHFFFAOYSA-N tolfenamic acid Chemical compound CC1=C(Cl)C=CC=C1NC1=CC=CC=C1C(O)=O YEZNLOUZAIOMLT-UHFFFAOYSA-N 0.000 description 1
- 229960002905 tolfenamic acid Drugs 0.000 description 1
- 108010014765 tomato lectin Proteins 0.000 description 1
- 201000006680 tooth agenesis Diseases 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 229960003181 treosulfan Drugs 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 230000005909 tumor killing Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 229960002004 valdecoxib Drugs 0.000 description 1
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 229940114727 vet one Drugs 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 238000000733 zeta-potential measurement Methods 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6883—Polymer-drug antibody conjugates, e.g. mitomycin-dextran-Ab; DNA-polylysine-antibody complex or conjugate used for therapy
- A61K47/6885—Polymer-drug antibody conjugates, e.g. mitomycin-dextran-Ab; DNA-polylysine-antibody complex or conjugate used for therapy the conjugate or the polymer being a starburst, a dendrimer, a cascade
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/595—Polyamides, e.g. nylon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G83/00—Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
- C08G83/002—Dendritic macromolecules
- C08G83/003—Dendrimers
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G83/00—Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
- C08G83/002—Dendritic macromolecules
- C08G83/003—Dendrimers
- C08G83/004—After treatment of dendrimers
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Biotechnology (AREA)
- Dermatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Description
本出願は、2017年11月10日に出願された米国出願第62/584,623号に基づく利点および優先権を主張し、この米国出願は、その全体が参照により援用される。
本発明は、国立衛生研究所によって付与されたGrant NIBIB-1R01EB018306-01、NICHD-1R01HD076901-01A1、および5R01EY025304-04に基づく政府支援のもとでなされた。政府は、本発明において一定の権利を有する。
2018年11月12日に作成され、3,792バイトのサイズを有する「JHU_C_14798_ST25.txt」の名称のテキストファイルとして提出された配列表は、37C.F.R.§1.52(e)(5)に従い、これにより参照により本明細書に組み込まれる。
本発明は、全般的に、分子送達システムの分野に関し、より詳細には、予防用、治療用、および/または診断用薬剤を対象の中枢神経系に送達し、疾患および/または状態を予防、処置、および/または診断するためのデンドリマーに関する。
少なくとも1OH基/nm3(ヒドロキシル基の数/体積nm3)の、好ましくは少なくとも5OH基/nm3の高密度ヒドロキシル基を有するデンドリマーを記載する。一般的に、これらのデンドリマーは、約500ダルトンから約100,000ダルトンの間、好ましくは約500ダルトンから約50,000ダルトンの間、最も好ましくは約1,000ダルトンから約10,000ダルトンの間の分子量を有する。典型的には、デンドリマーは、約1nmから約15nmの間、好ましくは約1nmから約5nmの間、最も好ましくは約1nmから約2nmの間の平均直径を有する。
本発明は、例えば、以下の項目を提供する。
(項目1)
複数のヒドロキシル基を含むデンドリマーであって、
少なくとも1OH基/nm 3 (ヒドロキシル基の数/体積nm 3 )のヒドロキシル(-OH)基体積密度を有するデンドリマー。
(項目2)
少なくとも5OH基/nm 3 のヒドロキシル(-OH)基体積密度を有する、項目1に記載のデンドリマー。
(項目3)
複数のヒドロキシル基を含むデンドリマーであって、
少なくとも1OH基/nm 2 (ヒドロキシル基の数/表面積nm 2 )のヒドロキシル(-OH)基表面密度を有するデンドリマー。
(項目4)
少なくとも3OH基/nm 2 のヒドロキシル(-OH)基表面密度を有する、項目3に記載のデンドリマー。
(項目5)
約500ダルトンから約100,000ダルトンの間の分子量を有する、項目1から4のいずれか一項に記載のデンドリマー。
(項目6)
約500ダルトンから約50,000ダルトンの間の分子量を有する、項目1から4のいずれか一項に記載のデンドリマー。
(項目7)
約1,000ダルトンから約10,000ダルトンの間の分子量を有する、項目1から4のいずれか一項に記載のデンドリマー。
(項目8)
約1nmから約15nmの間の直径を有する、項目1から7のいずれか一項に記載のデンドリマー。
(項目9)
約1nmから約5nmの間の直径を有する、項目1から7のいずれか一項に記載のデンドリマー。
(項目10)
約1nmから約2nmの間の直径を有する、項目1から7のいずれか一項に記載のデンドリマー。
(項目11)
(a)中心コア、(b)1つまたは複数の分岐単位、および(c)末端官能基を含むデンドリマーであって、
各(a)、(b)、および(c)が、独立して、エチレンジアミン、アクリル酸メチル、ジペンタエリスリトール、ペンタエリスリトール、2-(アミノメチル)-2-(ヒドロキシメチル)プロパン-1,3-ジオール、2-エチル-2-(ヒドロキシメチル)プロパン-1,3-ジオール、3,3’,3’’,3’’’-シランテトライルテトラキス(プロパン-1-チオール)、3,3-ジビニルペンタ-1,4-ジエン、3,3’,3’’-ニトリロトリプロピオン酸、3,3’,3’’-ニトリロトリス(N-(2-アミノエチル)プロパンアミド)、3,3’,3’’,3’’’-(エタン-1,2-ジイルビス(アザントリイル))テトラプロパンアミド、3-(カルボキシメチル)-3-ヒドロキシペンタン二酸、2,2’-((2,2-ビス((2-ヒドロキシエトキシ)メチル)プロパン-1,3-ジイル)ビス(オキシ))ビス(エタン-1-オール)、テトラキス(3-(トリクロロシリル)プロピル)シラン、1-チオグリセロール、2,2,4,4,6,6-ヘキサクロロ-1,3,5,2l5,4l5,6l5-トリアザトリホスフィニン、3-(ヒドロキシメチル)-5,5-ジメチルヘキサン-2,4-ジオール、4,4’,4’’-(エタン-1,1,1-トリイル)トリフェノール、2,4,6-トリクロロ-1,3,5-トリアジン、5-(ヒドロキシメチル)ベンゼン-1,2,3-トリオール、5-(ヒドロキシメチル)ベンゼン-1,3-ジオール、1,3,5-トリス(ジメチル(ビニル)シリル)ベンゼン、カルボシロキサンコア、ニトリロトリメタノール、エチレンジアミン、プロパン-1,3-ジアミン、ブタン-1,4-ジアミン、2,2’,2’’-ニトリロトリス(エタン-1-オール)、アルファシクロデキストリン、ベータシクロデキストリン、ガンマシクロデキストリン、ククルビツリル、ベンゼン-1,2,3,4,5,6-ヘキサチオール、単糖、二糖、三糖、オリゴ糖、キトサン、およびこれらの任意の誘導体からなる群から選択される、デンドリマー。
(項目12)
第1世代(G1)、G2、G3、G4、G5、G6、G7、G8、G9、G10デンドリマーである、項目11に記載のデンドリマー。
(項目13)
前記コアが、アルキン修飾ジペンタエリスリトールから調製される、項目11および12のいずれか一項に記載のデンドリマー。
(項目14)
前記1つまたは複数の分岐単位が、1つまたは複数のハイパーモノマーから調製される、項目11から13のいずれか一項に記載のデンドリマー。
(項目15)
前記1つまたは複数のハイパーモノマーが、1個のアジド官能基および5個のアリル基を含むAB 5 直交性ハイパーモノマーであり、5個のアリル基を有するジペンタエリスリトールをモノトシル化トリエチレングリコールアジドと反応させて調製される、項目14に記載のデンドリマー。
(項目16)
少なくとも1OH基/nm 2 の表面ヒドロキシル基密度を有する、項目11から15のいずれか一項に記載のデンドリマー。
(項目17)
ヒドロキシル基が、少なくとも7OH基/nm 2 の表面ヒドロキシル基密度を有する、項目11から15のいずれか一項に記載のデンドリマー。
(項目18)
約500ダルトンから約100,000ダルトンの間の分子量を有する、項目11から17のいずれか一項に記載のデンドリマー。
(項目19)
約500ダルトンから約50,000ダルトンの間の分子量を有する、項目11から17のいずれか一項に記載のデンドリマー。
(項目20)
約1,000ダルトンから約10,000ダルトンの間の分子量を有する、項目11から17のいずれか一項に記載のデンドリマー。
(項目21)
デンドロンの形態である、項目1から20のいずれか一項に記載のデンドリマー。
(項目22)
テクトデンドリマーにさらに組織化されている、項目1から20のいずれか一項に記載のデンドリマー。
(項目23)
デンドリマー中にカプセル化、会合、および/またはコンジュゲートされている1つまたは複数の予防用、治療用、および/または診断用薬剤を含む、項目1から22のいずれか一項に記載のデンドリマー。
(項目24)
前記1つまたは複数の予防用、治療用、および/または診断用薬剤が、約0.01重量%から約30重量%、好ましくは約1重量%から約20重量%、より好ましくは約5重量%から約20重量%の濃度で、デンドリマー中にカプセル化、会合、および/またはコンジュゲートされている、項目23に記載のデンドリマー。
(項目25)
前記1つまたは複数の予防用、治療用、および/または診断用薬剤が、必要に応じて1つまたは複数のスペーサーを介して、前記デンドリマーに共有結合によりコンジュゲートされている、項目23または24に記載のデンドリマー。
(項目26)
前記1つまたは複数の予防的、治療的、および/または診断的薬剤が、ジスルフィド、エステル、エーテル、チオエステル、カルバメート、カルボネート、ヒドラジン、およびアミドからなる群から選択される1つまたは複数の連結を介して、デンドリマーに共有結合によりコンジュゲートされている、項目23から25のいずれか一項に記載のデンドリマー。
(項目27)
前記スペーサーが、予防的、治療的、および/または診断的薬剤である、項目25に記載のデンドリマー。
(項目28)
前記スペーサーがN-アセチルシステインである、項目27に記載のデンドリマー。
(項目29)
前記1つまたは複数の治療剤が、抗炎症薬、化学療法薬、血管拡張薬、および抗感染症剤である、項目23から28のいずれか一項に記載のデンドリマー。
(項目30)
眼、脳および/または神経系(CNS)の1つまたは複数の疾患、状態、および/または傷害を処置、予防、および/またはイメージングするための方法であって、項目1から29のいずれか一項に記載の組成物を、それを必要とする対象に投与することを含む方法。
(項目31)
眼、脳および/または神経系の1つまたは複数の疾患、状態、および/または傷害が、活性化ミクログリアおよびアストロサイトと関連する疾患、状態、および傷害である、項目30に記載の方法。
(項目32)
デンドリマー組成物が、1つまたは複数の活性化ミクログリアおよびアストロサイトを標的とするのに有効な量である、項目30または31に記載の方法。
(項目33)
前記デンドリマー組成物が、眼、脳および/または神経系の1つまたは複数の疾患、状態、および/または傷害の1つまたは複数の症状を緩和するのに有効な量である、項目30から32のいずれか一項に記載の方法。
(項目34)
前記デンドリマー組成物が、静脈内投与される、項目30から33のいずれか一項に記載の方法。
(項目35)
高密度表面ヒドロキシル基を有するデンドリマーを作製する方法であって、
(a)第1のモノマーをプロパルギル化することによって1つまたは複数のハイパーコアを調製することであって、前記第1のモノマーが、プロパルギル化のための2つまたはそれを超える反応性基を含むこと、
(b)n個の反応性基にアリル基をコンジュゲートし、第2のモノマーの反応性基のうちの1つに1個のアジド基をコンジュゲートすることによって、(n+1)個の反応性基を有する前記第2のモノマーから1つまたは複数のハイパーモノマーAB n を調製すること(nは、2であるかまたはそれを超える)、
(c)第1世代デンドリマーを得るために、銅(I)触媒アルキンアジドクリックケミストリーのためにハイパーコアおよびハイパーモノマーを混合すること、
(d)第2世代デンドリマーを得るために、チオール-エンクリックケミストリーのために第1世代デンドリマーを第3のモノマーと混合することであって、前記第3のモノマーが、少なくともチオール基および少なくとも1つのヒドロキシル基を含むこと
を含む方法。
(項目36)
前記第1、第2、および第3のモノマーが、独立して、ジペンタエリスリトール、ペンタエリスリトール、2-(アミノメチル)-2-(ヒドロキシメチル)プロパン-1,3-ジオール、2-エチル-2-(ヒドロキシメチル)プロパン-1,3-ジオール、3,3’,3’’,3’’’-シランテトライルテトラキス(プロパン-1-チオール)、3,3-ジビニルペンタ-1,4-ジエン、3,3’,3’’ニトリロトリプロピオン酸、3,3’,3’’-ニトリロトリス(N-(2-アミノエチル)プロパンアミド)、3,3’,3’’,3’’’-(エタン-1,2-ジイルビス(アザントリイル))テトラプロパンアミド、3-(カルボキシメチル)-3-ヒドロキシペンタン二酸、2,2’-((2,2-ビス((2-ヒドロキシエトキシ)メチル)プロパン-1,3-ジイル)ビス(オキシ))ビス(エタン-1-オール)、テトラキス(3-(トリクロロシリル)プロピル)シラン、1-チオグリセロール、2,2,4,4,6,6-ヘキサクロロ-1,3,5,2l5,4l5,6l5-トリアザトリホスフィニン、3-(ヒドロキシメチル)-5,5-ジメチルヘキサン-2,4-ジオール、4,4’,4’’-(エタン-1,1,1-トリイル)トリフェノール、2,4,6-トリクロロ-1,3,5-トリアジン、5-(ヒドロキシメチル)ベンゼン-1,2,3-トリオール、5-(ヒドロキシメチル)ベンゼン-1,3-ジオール、1,3,5-トリス(ジメチル(ビニル)シリル)ベンゼン、カルボシロキサンコア、ニトリロトリメタノール、エチレンジアミン、プロパン-1,3-ジアミン、ブタン-1,4-ジアミン、2,2’,2’’-ニトリロトリス(エタン-1-オール)、アルファシクロデキストリン、ベータシクロデキストリン、ガンマシクロデキストリン、ククルビツリル、ベンゼン-1,2,3,4,5,6-ヘキサチオール、単糖、二糖、三糖、オリゴ糖、キトサン、およびこれらの任意の誘導体からなる群から選択される、項目35に記載の方法。
(項目37)
前記1つまたは複数ののハイパーモノマーAB n が、AB 2 、AB 3 、AB 4 、AB 5 、AB 6 、AB 7 、およびAB 8 である、項目35または36に記載の方法。
(項目38)
前記1つまたは複数のハイパーモノマーがAB 5 である、項目33から35のいずれか一項に記載の方法。
(項目39)
前記第1のモノマーおよび前記第2のモノマーが、ジペンタエリスリトールであり、前記第3のモノマーが1-チオグリセロールである、項目35から38のいずれか一項に記載の方法。
(項目40)
前記デンドリマーが、1つまたは複数の治療的、予防的、および/または診断的薬剤に、さらに複合体化および/またはコンジュゲートされる、項目35から39のいずれか一項に記載の方法。
I.定義
「薬学的に許容される」という用語は、食品医薬品局などの政府機関のガイドラインに従って、過剰な毒性、刺激、アレルギー応答、または他の問題もしくは合併症がなく、妥当な利点/リスク比率と釣り合いがとれた、ヒトおよび動物の組織との接触での使用に好適な健全な医学的判断の範囲内での化合物、材料、組成物、および/または投薬形態を指す。「担体」または「賦形剤」という用語は、1つまたは複数の活性成分を組み合わせた製剤中の有機または無機、天然または合成不活性成分を指す。一部の実施形態では、担体または賦形剤は、医薬組成物に添加され、化合物の投与を促進する非活性物質であり、および/または生物に顕著な刺激をもたらすことがなく、投与された化合物の生物活性および特性を無効にしない。
II.組成物
A.デンドリマー
1.中心コア
3.表面基
B.カップリング剤およびスペーサー
C.治療的、予防的および診断的薬剤
1.治療剤
a.抗炎症剤
b.化学療法剤
c.神経活性化剤
d.抗感染症剤
2.診断用薬剤
D.賦形剤およびデバイス
1.非経口投与
2.経腸投与
3.局所投与
III.デンドリマーナノ粒子を作製するための方法
A.デンドリマー
B.デンドリマー複合体
IV.使用方法
A.処置する方法
B.処置されることになる状態
1.眼疾患および傷害
2.神経疾患および神経変性疾患
3.神経発達障害
4.脳腫瘍
5.胃腸障害
C.投薬量および有効量
D.対照
E.組合せ
第2世代の高密度なポリヒドロキシデンドリマー(D2-OH-60、PEGOL-60としても知られる)の合成
方法および材料
試薬
臭化プロパルギル溶液(80wt%、トルエン中)、臭化アリル、水素化ナトリウム(60%分散体、鉱物油中)、2,2-ジメトキシ-2-フェニルアセトフェノン、1-チオグリセロール、N-(3-ジメチルアミノプロピル)-N’-エチルカルボジイミド塩酸塩(EDC)、4-(ジメチルアミノ)ピリジン(DMAP)、N,N’-ジイソプロピルエチルアミン(DIPEA)、塩化p-トルエンスルホニル、テトラエチレングリコール、トリフルオロ酢酸(TFA)、γ-(Boc-アミノ)酪酸(BOC-GABA-OH)、硫酸銅五水和物、アスコルビン酸ナトリウム、無水ジクロロメタン(DCM)、無水テトラヒドロフラン(THF)、および無水ジメチルホルムアミド(DMF)は、Sigma-Aldrich(St.Louis、MO、USA)から購入した。Cy5-モノ-NHSエステルおよびFITCは、Amersham Biosciences-GE Healthcareから購入した。全ての他のACSグレード溶媒は、Fisher Scientificから入手した。重水素化溶媒のジメチルスルホキシド(DMSO-d6)、水(D2O)、メタノール(CD3OD)、およびクロロホルム(CDCl3)は、Cambridge Isotope Laboratories,Inc.(Andover、Massachusetts)から購入した。透析膜(MWカットオフ1000Da)は、Spectrum Laboratories Inc.(Rancho Dominguez、CA、USA)から得た。
中間体およびデンドリマーの合成
動的光散乱(DLS)およびゼータ電位(ζ)
核磁気共鳴(1Hおよび13C{1H}NMR)
高性能液体クロマトグラフィー(HPLC)
質量分光法
結果
(実施例2)
蛍光造影剤のデンドリマーナノ粒子へのコンジュゲート
方法および材料
中間体およびデンドリマーの合成
結果
脳におけるD2-OH-60-Cy5の定性的脳分布
方法および材料
CPウサギモデルおよびD2-OH-60-cy5の投与
免疫組織化学
結果
(実施例4)
脳および主要臓器におけるD2-OH-60-Cy5、ビス-MPA-G4-OH64-Cy5、およびPAMAM-G4-OH64-Cy5の定量的生体内分布の比較
方法および材料
(実施例5)
眼におけるPEGOL-60-Cy5の定性的分布
方法および材料
ラット脂質注射AMDモデルおよびPEGOL-60-Cy5の投与
組織の処理、免疫組織化学および共焦点イメージング
結果
(実施例6)
神経膠芽腫(GBM)マウスモデルにおいて腫瘍関連マクロファージを標的とするPEGOL-60-Cy5
方法および材料
GBMマウスモデルおよびPEGOL-60-Cy5の投与
GBMモデルに関する免疫組織化学および共焦点イメージング
結果
(実施例7)
PEGOL-60の抗酸化および抗炎症活性のin vitro評価
方法および材料
細胞培養
細胞毒性評価
LPS刺激および評価
酸化ストレス誘発性の細胞死
結果
(実施例8)
PEGOL-60のin vivo有効性および安全性プロファイル
方法および材料
PEGOL-60のin vivo投与
行動試験
ベースラインからの変化(48)=スコア(48時間)-スコア(0時間)またはベースラインからの変化(96)=スコア(96時間)-スコア(0時間)
リアルタイムPCR
TNF-α(フォワード)TAGTAGCAAACCCGCAAGTG(配列番号11)、
TNF-α(リバース)CTGAAGAGAACCTGGGAGTAGA(配列番号12)。
IL-1β(フォワード)TGCCAACCCTACAACAAGAG(配列番号13)、
IL-1β(リバース)AAAGTTCTCAGGCCGTCATC(配列番号14)。
IL-6(フォワード)CATCAAGGAGCTGAGGAAAGAG(配列番号15)、
IL-6(リバース)CCTTGGAAGGTGCAGATTGA(配列番号16)。
GAPDH(フォワード)TGACGACATCAAGAAGGTGGTG(配列番号17)、
GAPDH(リバース)GAAGGTGGAGGAGTGGGTGTC(配列番号18)。
結果
(実施例9)
脳性麻痺(CP)の新生ウサギモデルにおけるPEGOL-60-Cy5生体内分布の定性的脳分布
方法および材料
CPウサギモデルおよびPEGOL-60-Cy5の投与
CPモデルに関する免疫組織化学
CP仔ウサギ脳の顕微解剖の手順
組織試料からのデンドリマーの抽出
蛍光定量化
結果
(実施例10)
大規模なデンドリマー-薬物合成に関する頑強な合成戦略
方法および材料
中間体およびデンドリマー-薬物コンジュゲートの合成
結果
戦略1:エステルリンカーを介したD-NAC
合成時間の短縮
経済的で産業において用い易いプロトコール
戦略2:エーテルリンカーを介したD-NACおよび銅不含チオール-エンクリックケミストリー
Claims (36)
- 眼、脳および/または中枢神経系(CNS)の1つまたは複数の疾患、状態、および/または傷害の処置、予防、および/またはイメージングにおける使用のための組成物であって、前記組成物が、複数のヒドロキシル基を含む非ポリ(アミドアミン)デンドリマーを含み、
動的光散乱によって決定される前記デンドリマーのサイズに基づき決定される少なくとも4OH基/nm2のヒドロキシル(OH)基表面密度を有し、1つまたは複数の予防用、治療用、または診断用薬剤が、前記デンドリマー中にカプセル化、前記デンドリマーと会合、または前記デンドリマーにコンジュゲートされており、
前記デンドリマーが、中枢神経系、脳または眼の炎症部位における活性化細胞に選択的に取り込まれる、組成物。 - 動的光散乱によって決定される前記デンドリマーのサイズに基づき決定される1以上のOH基/nm3のヒドロキシル基体積密度を有する、請求項1に記載の組成物。
- 少なくとも10OH基/nm2のヒドロキシル基表面密度を有する、請求項1に記載の組成物。
- 約4から15OH基/nm2の間のヒドロキシル基表面密度を有する、請求項1に記載の組成物。
- 約500ダルトンから約100,000ダルトンの間の分子量を有する、請求項1から4のいずれか一項に記載の組成物。
- 約500ダルトンから約50,000ダルトンの間の分子量を有する、請求項1から4のいずれか一項に記載の組成物。
- 約1,000ダルトンから約10,000ダルトンの間の分子量を有する、請求項1から4のいずれか一項に記載の組成物。
- 約1nmから約15nmの間の直径を有する、請求項1から7のいずれか一項に記載の組成物。
- 約1nmから約5nmの間の直径を有する、請求項1から7のいずれか一項に記載の組成物。
- 約1nmから約2nmの間の直径を有する、請求項1から7のいずれか一項に記載の組成物。
- 前記デンドリマーが、アクリル酸メチル、ジペンタエリスリトール、ペンタエリスリトール、2-(アミノメチル)-2-(ヒドロキシメチル)プロパン-1,3-ジオール、2-エチル-2-(ヒドロキシメチル)プロパン-1,3-ジオール、3,3’,3’’,3’’’-シランテトライルテトラキス(プロパン-1-チオール)、3,3-ジビニルペンタ-1,4-ジエン、3,3’,3’’-ニトリロトリプロピオン酸、3,3’,3’’-ニトリロトリス(N-(2-アミノエチル)プロパンアミド)、3,3’,3’’,3’’’-(エタン-1,2-ジイルビス(アザントリイル))テトラプロパンアミド、3-(カルボキシメチル)-3-ヒドロキシペンタン二酸、2,2’-((2,2-ビス((2-ヒドロキシエトキシ)メチル)プロパン-1,3-ジイル)ビス(オキシ))ビス(エタン-1-オール)、テトラキス(3-(トリクロロシリル)プロピル)シラン、1-チオグリセロール、3-(ヒドロキシメチル)-5,5-ジメチルヘキサン-2,4-ジオール、4,4’,4’’-(エタン-1,1,1-トリイル)トリフェノール、2,4,6-トリクロロ-1,3,5-トリアジン、5-(ヒドロキシメチル)ベンゼン-1,2,3-トリオール、5-(ヒドロキシメチル)ベンゼン-1,3-ジオール、1,3,5-トリス(ジメチル(ビニル)シリル)ベンゼン、カルボシロキサン、ニトリロトリメタノール、プロパン-1,3-ジアミン、ブタン-1,4-ジアミン、2,2’,2’’-ニトリロトリス(エタン-1-オール)、アルファシクロデキストリン、ベータシクロデキストリン、ガンマシクロデキストリン、ククルビツリル、ベンゼン-1,2,3,4,5,6-ヘキサチオール、単糖、二糖、三糖、オリゴ糖、キトサン、ポリエチレングリコール、およびこれらの誘導体からなる群から選択される1つまたは複数の化合物から調製され、ここで前記誘導体が、加水分解、還元、または酸化産物である、請求項1~10のいずれか一項に記載の組成物。
- 眼、脳および/または中枢神経系(CNS)の1つまたは複数の疾患、状態、および/または傷害の処置、予防、および/またはイメージングにおける使用のための組成物であって、前記組成物が、中心コア、1つまたは複数の分岐単位、および末端ヒドロキシル基を含む非ポリ(アミドアミン)デンドリマーを含み、
前記中心コアが、アクリル酸メチル、ジペンタエリスリトール、ペンタエリスリトール、2-(アミノメチル)-2-(ヒドロキシメチル)プロパン-1,3-ジオール、2-エチル-2-(ヒドロキシメチル)プロパン-1,3-ジオール、3,3’,3’’,3’’’-シランテトライルテトラキス(プロパン-1-チオール)、3,3-ジビニルペンタ-1,4-ジエン、3,3’,3’’-ニトリロトリプロピオン酸、3,3’,3’’-ニトリロトリス(N-(2-アミノエチル)プロパンアミド)、3,3’,3’’,3’’’-(エタン-1,2-ジイルビス(アザントリイル))テトラプロパンアミド、3-(カルボキシメチル)-3-ヒドロキシペンタン二酸、2,2’-((2,2-ビス((2-ヒドロキシエトキシ)メチル)プロパン-1,3-ジイル)ビス(オキシ))ビス(エタン-1-オール)、テトラキス(3-(トリクロロシリル)プロピル)シラン、1-チオグリセロール、3-(ヒドロキシメチル)-5,5-ジメチルヘキサン-2,4-ジオール、4,4’,4’’-(エタン-1,1,1-トリイル)トリフェノール、2,4,6-トリクロロ-1,3,5-トリアジン、5-(ヒドロキシメチル)ベンゼン-1,2,3-トリオール、5-(ヒドロキシメチル)ベンゼン-1,3-ジオール、1,3,5-トリス(ジメチル(ビニル)シリル)ベンゼン、カルボシロキサンコア、ニトリロトリメタノール、プロパン-1,3-ジアミン、ブタン-1,4-ジアミン、2,2’,2’’-ニトリロトリス(エタン-1-オール)、アルファシクロデキストリン、ベータシクロデキストリン、ガンマシクロデキストリン、ククルビツリル、ベンゼン-1,2,3,4,5,6-ヘキサチオール、単糖、二糖、三糖、オリゴ糖、キトサン、およびこれらの任意の誘導体からなる群から選択される化合物から調製され、ここで前記誘導体が、加水分解、還元、または酸化産物であり、
前記1つまたは複数の分岐単位が直鎖状または分岐状ポリエチレングリコールを含み、
前記デンドリマーが、動的光散乱によって決定される前記デンドリマーのサイズに基づき決定される少なくとも4OH基/nm2のヒドロキシル基表面密度を有し、
1つまたは複数の予防用、治療用、または診断用薬剤が、前記デンドリマー中にカプセル化、前記デンドリマーと会合、または前記デンドリマーにコンジュゲートされており、
前記デンドリマーが、中枢神経系、脳または眼の炎症部位における活性化細胞に選択的に取り込まれる、組成物。 - 前記中心コアが、ジペンタエリスリトール、ペンタエリスリトール、またはこれらの任意の誘導体から調製され、ここで前記誘導体が、加水分解、還元、または酸化産物である、請求項12に記載の組成物。
- 前記コアが、アルキン修飾ジペンタエリスリトールから調製される、請求項12または13に記載の組成物。
- 前記1つまたは複数の分岐単位が、1つまたは複数のハイパーモノマーから調製される、請求項12から14のいずれか一項に記載の組成物。
- 前記1つまたは複数のハイパーモノマーが、1個のアジド官能基および5個のアリル基を含むAB5直交性ハイパーモノマーであり、5個のアリル基を有するジペンタエリスリトールをモノトシル化トリエチレングリコールアジドと反応させて調製される、請求項15に記載の組成物。
- 4から15OH基/nm2の表面ヒドロキシル基密度を有する、請求項12から16のいずれか一項に記載の組成物。
- 前記デンドリマーが、少なくとも7OH基/nm2の表面ヒドロキシル基密度を有する、請求項12から16のいずれか一項に記載の組成物。
- 約500ダルトンから約100,000ダルトンの間の分子量を有する、請求項12から18のいずれか一項に記載の組成物。
- 約500ダルトンから約50,000ダルトンの間の分子量を有する、請求項12から18のいずれか一項に記載の組成物。
- 約1,000ダルトンから約10,000ダルトンの間の分子量を有する、請求項12から18のいずれか一項に記載の組成物。
- デンドロンの形態である、請求項1から21のいずれか一項に記載の組成物。
- テクトデンドリマーにさらに組織化されている、請求項1から21のいずれか一項に記載の組成物。
- 前記1つまたは複数の予防用、治療用、および/または診断用薬剤が、約0.01重量%から約30重量%の濃度で、デンドリマー中にカプセル化、デンドリマーと会合、および/またはデンドリマーにコンジュゲートされている、請求項1から23のいずれか一項に記載の組成物。
- 前記1つまたは複数の予防用、治療用、および/または診断用薬剤が、前記デンドリマーに共有結合によりコンジュゲートされている、請求項1から24のいずれか一項に記載の組成物。
- 前記1つまたは複数の予防的、治療的、および/または診断的薬剤が、ジスルフィド、エステル、エーテル、チオエステル、カルバメート、カルボネート、ヒドラジン、およびアミドからなる群から選択される1つまたは複数の連結を介して、デンドリマーに共有結合によりコンジュゲートされている、請求項1から25のいずれか一項に記載の組成物。
- 前記1つまたは複数の予防的、治療的、および/または診断的薬剤が、1つまたは複数のスペーサーを介して共有結合によりコンジュゲートされており、前記スペーサーが、予防的、治療的、および/または診断的薬剤である、請求項25に記載の組成物。
- 前記スペーサーがN-アセチルシステインである、請求項27に記載の組成物。
- 前記1つまたは複数の治療剤が、抗炎症薬、化学療法薬、血管拡張薬、および抗感染症剤である、請求項1から28のいずれか一項に記載の組成物。
- 活性化マクロファージ、活性化ミクログリア、および/または炎症部位における網膜色素上皮(RPE)の細胞に選択的に取り込まれる、請求項1から29のいずれか一項に記載の組成物。
- 眼、脳および/または中枢神経系の1つまたは複数の疾患、状態、および/または傷害が、活性化ミクログリアおよびアストロサイトと関連する疾患、状態、および傷害であり、前記デンドリマーが前記活性化ミクログリアおよびアストロサイトを標的とする、請求項1~30のいずれか一項に記載の組成物。
- 請求項1~30のいずれか一項に記載の組成物を作製する方法であって、
(a)第1のモノマーをプロパルギル化することによって1つまたは複数のハイパーコアを調製することであって、前記第1のモノマーが、プロパルギル化のための2つまたはそれを超える反応性基を含むこと、
(b)n個の反応性基にアリル基をコンジュゲートし、第2のモノマーの反応性基のうちの1つに1個のアジド基をコンジュゲートすることによって、(n+1)個の反応性基を有する前記第2のモノマーから1つまたは複数のハイパーモノマーABnを調製すること(nは、2であるかまたはそれを超える)、
(c)第1世代デンドリマーを得るために、銅(I)触媒アルキンアジドクリックケミストリーのためにハイパーコアおよびハイパーモノマーを混合すること、
(d)第2世代デンドリマーを得るために、チオール-エンクリックケミストリーのために第1世代デンドリマーを第3のモノマーと混合することであって、前記第3のモノマーが、少なくともチオール基および少なくとも1つのヒドロキシル基を含み、1つまたは複数のハイパーモノマーABnが、直鎖状または分岐状ポリエチレングリコールを含むこと、
(e)所望の世代のデンドリマーを得るのに必要なプロセスを繰り返すこと、
(f)前記所望の世代のデンドリマーを1つまたは複数の予防的、治療的、または診断的薬剤とコンジュゲートさせることを含む方法。 - 前記第1、第2、および第3のモノマーが、独立して、ジペンタエリスリトール、ペンタエリスリトール、2-(アミノメチル)-2-(ヒドロキシメチル)プロパン-1,3-ジオール、2-エチル-2-(ヒドロキシメチル)プロパン-1,3-ジオール、3,3’,3’’,3’’’-シランテトライルテトラキス(プロパン-1-チオール)、3,3-ジビニルペンタ-1,4-ジエン、3,3’,3’’ニトリロトリプロピオン酸、3,3’,3’’-ニトリロトリス(N-(2-アミノエチル)プロパンアミド)、3,3’,3’’,3’’’-(エタン-1,2-ジイルビス(アザントリイル))テトラプロパンアミド、3-(カルボキシメチル)-3-ヒドロキシペンタン二酸、2,2’-((2,2-ビス((2-ヒドロキシエトキシ)メチル)プロパン-1,3-ジイル)ビス(オキシ))ビス(エタン-1-オール)、テトラキス(3-(トリクロロシリル)プロピル)シラン、1-チオグリセロール、3-(ヒドロキシメチル)-5,5-ジメチルヘキサン-2,4-ジオール、4,4’,4’’-(エタン-1,1,1-トリイル)トリフェノール、2,4,6-トリクロロ-1,3,5-トリアジン、5-(ヒドロキシメチル)ベンゼン-1,2,3-トリオール、5-(ヒドロキシメチル)ベンゼン-1,3-ジオール、1,3,5-トリス(ジメチル(ビニル)シリル)ベンゼン、カルボシロキサンコア、ニトリロトリメタノール、プロパン-1,3-ジアミン、ブタン-1,4-ジアミン、2,2’,2’’-ニトリロトリス(エタン-1-オール)、アルファシクロデキストリン、ベータシクロデキストリン、ガンマシクロデキストリン、ククルビツリル、ベンゼン-1,2,3,4,5,6-ヘキサチオール、単糖、二糖、三糖、オリゴ糖、キトサン、およびこれらの任意の誘導体からなる群から選択される、請求項32に記載の方法。
- 前記1つまたは複数のハイパーモノマーABnが、AB2、AB3、AB4、AB5、AB6、AB7、およびAB8である、請求項32または33に記載の方法。
- 前記1つまたは複数のハイパーモノマーがAB5である、請求項32から34のいずれか一項に記載の方法。
- 前記第1のモノマーおよび前記第2のモノマーが、ジペンタエリスリトールであり、前記第3のモノマーが1-チオグリセロールである、請求項32から35のいずれか一項に記載の方法。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2023036541A JP2023071973A (ja) | 2017-11-10 | 2023-03-09 | デンドリマー送達システムおよびそれを使用する方法 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201762584623P | 2017-11-10 | 2017-11-10 | |
US62/584,623 | 2017-11-10 | ||
PCT/US2018/060795 WO2019094952A1 (en) | 2017-11-10 | 2018-11-13 | Dendrimer delivery system and methods of use thereof |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2023036541A Division JP2023071973A (ja) | 2017-11-10 | 2023-03-09 | デンドリマー送達システムおよびそれを使用する方法 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2021502451A JP2021502451A (ja) | 2021-01-28 |
JP2021502451A5 JP2021502451A5 (ja) | 2021-12-23 |
JP7383297B2 true JP7383297B2 (ja) | 2023-11-20 |
Family
ID=64572537
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020525944A Active JP7383297B2 (ja) | 2017-11-10 | 2018-11-13 | デンドリマー送達システムおよびそれを使用する方法 |
JP2023036541A Pending JP2023071973A (ja) | 2017-11-10 | 2023-03-09 | デンドリマー送達システムおよびそれを使用する方法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2023036541A Pending JP2023071973A (ja) | 2017-11-10 | 2023-03-09 | デンドリマー送達システムおよびそれを使用する方法 |
Country Status (8)
Country | Link |
---|---|
US (1) | US11918657B2 (ja) |
EP (1) | EP3707193A1 (ja) |
JP (2) | JP7383297B2 (ja) |
CN (1) | CN111615528A (ja) |
AU (2) | AU2018365250B2 (ja) |
CA (1) | CA3082121C (ja) |
IL (1) | IL274390A (ja) |
WO (1) | WO2019094952A1 (ja) |
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP7178108B2 (ja) * | 2017-04-27 | 2022-11-25 | ザ・ジョンズ・ホプキンス・ユニバーシティー | 血管造影において使用するためのデンドリマー組成物 |
PL239642B1 (pl) * | 2018-08-16 | 2021-12-20 | Pomorski Univ Medyczny W Szczecinie | Kompozycja do doszklistkowego podawania białka leczniczego |
CA3163889A1 (en) | 2019-12-04 | 2021-06-10 | Ashvattha Therapeutics, Inc. | Triantennary n-acetylgalactosamine modified hydroxyl polyamidoamine dendrimers and methods of use thereof |
AU2020396561A1 (en) | 2019-12-04 | 2022-07-14 | Ashvattha Therapeutics, Inc. | Dendrimer compositions and methods for drug delivery to the eye |
US20210170040A1 (en) * | 2019-12-04 | 2021-06-10 | Ashvattha Therapeutics, Inc. | Dendrimer compositions and methods for drug delivery |
US11523767B2 (en) * | 2020-01-28 | 2022-12-13 | University of Pittsburgh—of the Commonwealth System of Higher Education | System, method, and computer program product for detecting neurodegeneration using differential tractography |
EP4138821A1 (en) | 2020-04-24 | 2023-03-01 | The Johns Hopkins University | Compositions and methods comprising dendrimers and therapeutic agents |
AU2021259877A1 (en) | 2020-04-24 | 2022-12-08 | Ashvattha Therapeutics, Inc. | Dendrimer compositions and methods for treatment of severe acute respiratory distress syndrome |
EP4210764A1 (en) * | 2020-09-08 | 2023-07-19 | The Johns Hopkins University | Galactosylated dendrimers for targeted intracellular delivery to hepatocytes |
WO2022094327A1 (en) * | 2020-10-30 | 2022-05-05 | Ashvattha Therapeutics, Inc. | Radiolabeled ether dendrimer conjugates for pet imaging and radiotherapy |
US20240041860A1 (en) * | 2020-12-02 | 2024-02-08 | The Johns Hopkins University | Restoration of motor function post-neurological injury using psychedelics |
WO2023049743A1 (en) | 2021-09-21 | 2023-03-30 | The Johns Hopkins University | Dendrimer conjugates of small molecule biologics for intracellular delivery |
WO2023122599A1 (en) | 2021-12-20 | 2023-06-29 | The Johns Hopkins University | Glycosylated dendrimers for targeted intracellular delivery |
WO2024020597A1 (en) | 2022-07-22 | 2024-01-25 | The Johns Hopkins University | Dendrimer-enabled targeted intracellular crispr/cas system delivery and gene editing |
WO2024044756A1 (en) | 2022-08-26 | 2024-02-29 | The Johns Hopkins University | Dendrimer compositions for targeted delivery of psychedelic therapeutics |
WO2024044760A1 (en) | 2022-08-26 | 2024-02-29 | The Johns Hopkins University | Dendrimer conjugates of antidepressant and antipsychotic agents and their methods of use |
WO2024044776A1 (en) | 2022-08-26 | 2024-02-29 | The Johns Hopkins University | Cannabinoid dendrimer compositions for targeted delivery |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017074993A1 (en) | 2015-10-29 | 2017-05-04 | The Johns Hopkins University | Denderimer compositions and use in treatment of necrotizing enterocolitis and other gastrointestinal disorders |
JP2017525763A (ja) | 2014-08-22 | 2017-09-07 | インスティトゥート ディンベスティガシオ ビオメディカ デ ベルビッチェ(イディベル) | 感染症の予防および/または治療のための方法および試薬 |
JP2017529325A (ja) | 2014-08-13 | 2017-10-05 | ザ・ジョンズ・ホプキンス・ユニバーシティー | 神経障害およびcns障害の処置におけるデンドリマー組成物および使用 |
Family Cites Families (49)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2093165C1 (ru) | 1993-07-06 | 1997-10-20 | Линд Роберт Мейнгардтович | Средство для лечения конъюнктивитов |
US6585956B2 (en) | 1997-07-07 | 2003-07-01 | The Dow Chemical Company | Dendritic-platinate drug delivery system |
WO2000018394A1 (en) | 1998-09-28 | 2000-04-06 | The Johns Hopkins University | Adrenoleukodystrophy treatments and drug screening |
US6312725B1 (en) | 1999-04-16 | 2001-11-06 | Cohesion Technologies, Inc. | Rapid gelling biocompatible polymer composition |
US6726918B1 (en) | 2000-07-05 | 2004-04-27 | Oculex Pharmaceuticals, Inc. | Methods for treating inflammation-mediated conditions of the eye |
JP2004523624A (ja) | 2001-02-26 | 2004-08-05 | デューク ユニバーシティ | 新規なデンドリティックポリマー、およびその生物医学的使用 |
US7261875B2 (en) | 2001-12-21 | 2007-08-28 | Board Of Regents, The University Of Texas System | Dendritic poly (amino acid) carriers and methods of use |
US20030180250A1 (en) | 2002-03-22 | 2003-09-25 | Council Of Scientific And Industrial Research | Compositions and complexes containing a macromolecular compound as potential anti-inflammatory agents |
US20040151754A1 (en) | 2002-12-20 | 2004-08-05 | Control Delivery Systems, Inc. | Steroid suspensions for intraocular use |
US20040180852A1 (en) | 2003-03-10 | 2004-09-16 | Cara-Lynne Schengrund | Use of multivalent glycodendrimers to inhibit the activity of human immunodeficiency virus |
EP1689354A4 (en) | 2003-11-20 | 2010-07-14 | Othera Holding Inc | REDUCTION OF CATARACTS, MACULAR GENERATION AND OTHER EYES DISEASES |
EP1711197A4 (en) | 2003-12-23 | 2008-11-05 | Musc Found For Res Dev | METHODS AND COMPOSITIONS FOR THE PREVENTION AND TREATMENT OF INFLAMMATORY DISEASES OR DISORDERS |
CA2554729A1 (en) | 2004-01-27 | 2005-08-11 | University Of Southern California | Polymer-bound antibody cancer therapeutic agent |
US7985424B2 (en) * | 2004-04-20 | 2011-07-26 | Dendritic Nanotechnologies Inc. | Dendritic polymers with enhanced amplification and interior functionality |
ES2547220T3 (es) * | 2004-04-20 | 2015-10-02 | Dendritic Nanotechnologies, Inc. | Polímeros dendríticos con amplificación y funcionalidad interior mejoradas |
US20050276917A1 (en) | 2004-06-15 | 2005-12-15 | Helene Bolm | Process for the preparation of powder coatings |
EP1676569A1 (en) | 2004-12-30 | 2006-07-05 | Pevion Biotech Ltd. | Lyophilization of virosomes |
EP1877103A4 (en) | 2005-04-20 | 2010-11-03 | Dendritic Nanotechnologies Inc | DENDRITIC POLYMERS WITH ENHANCED INNER FUNCTIONALITY AND AMPLIFICATION |
US7674781B2 (en) | 2006-04-28 | 2010-03-09 | Heather Sheardown | Hyaluronic acid-retaining polymers |
WO2007137260A2 (en) | 2006-05-22 | 2007-11-29 | Elan Pharmaceuticals, Inc. | Preparation of polymer conjugates of vla-4 antagonists via a mitsunobu' s reaction |
EP2319517B1 (en) | 2006-06-01 | 2013-09-11 | Novagali Pharma S.A. | Use of prodrugs for ocular intravitreous administration |
JP5484339B2 (ja) | 2007-10-05 | 2014-05-07 | ウェイン ステート ユニバーシティー | 合成物の持続的な放出のためのデンドリマー |
EP2261290B1 (en) | 2008-04-04 | 2016-02-24 | Konica Minolta IJ Technologies, Inc. | Nonaqueous ink jet ink, process for producing nonaqueous ink jet ink, and ink jet recording method |
WO2009142754A1 (en) | 2008-05-22 | 2009-11-26 | Goverment Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Dendritic conjugates and methods of use |
US20100015231A1 (en) | 2008-07-17 | 2010-01-21 | E.I. Du Pont De Nemours And Company | Low swell, long-lived hydrogel sealant |
US8821870B2 (en) | 2008-07-18 | 2014-09-02 | Allergan, Inc. | Method for treating atrophic age related macular degeneration |
WO2010039861A2 (en) | 2008-09-30 | 2010-04-08 | The Regents Of The University Of Michigan | Dendrimer conjugates |
WO2010147831A1 (en) | 2009-06-15 | 2010-12-23 | Wayne State University | Dendrimer based nanodevices for therapeutic and imaging purposes |
US7910393B2 (en) | 2009-06-17 | 2011-03-22 | Innovalight, Inc. | Methods for forming a dual-doped emitter on a silicon substrate with a sub-critical shear thinning nanoparticle fluid |
US20120177593A1 (en) | 2009-07-20 | 2012-07-12 | The Regents Of The University Of Michigan | Synthesis of dendrimer conjugates |
WO2011072290A2 (en) | 2009-12-11 | 2011-06-16 | The Regents Of The University Of Michigan | Targeted dendrimer-drug conjugates |
CA2830052C (en) | 2010-03-31 | 2018-10-09 | Wayne State University | Injectable dendrimer hydrogel nanoparticles |
CN103221535A (zh) | 2010-09-16 | 2013-07-24 | 康奈尔大学 | 腺苷受体信号转导调节血脑屏障通透性的用途 |
US8802072B2 (en) | 2011-04-13 | 2014-08-12 | Massachusetts Institute Of Technology | Biocompatible adhesive materials and methods |
US20130123330A1 (en) | 2011-07-15 | 2013-05-16 | Patrick Y. Lu | Dual Targeted siRNA Therapeutics for Treatment of Diabetic Retinopathy and Other Ocular Neovascularization Diseases |
CN103285408A (zh) | 2011-12-17 | 2013-09-11 | 倪明 | Fitc-葡聚糖在制备眼底血管造影剂方面的应用 |
JP2015526434A (ja) | 2012-08-14 | 2015-09-10 | アンジオケム インコーポレーテッド | ペプチド−デンドリマーコンジュゲート及びその使用 |
US20150352230A1 (en) | 2013-01-11 | 2015-12-10 | The Regents Of The University Of Michigan | Synthesis and isolation of dendrimer based imaging systems |
WO2014178892A1 (en) | 2013-05-03 | 2014-11-06 | Scanlan Thomas S | Use of sobetirome in the treatment of x-linked adrenolenoleukodystrophy |
AU2014276379A1 (en) | 2013-06-07 | 2016-01-07 | The Administrators Of The Tulane Educational Fund | Analogs of pituitary adenylate cyclase-activating polypeptide (PACAP) and methods for their use |
WO2015027068A1 (en) | 2013-08-21 | 2015-02-26 | Concordia University | Dendrimer-resveratrol complex |
US10029014B2 (en) | 2013-09-10 | 2018-07-24 | The Research Foundation For The State University Of New York | Synthesis of novel asymmetric bow-tie PAMAM dendrimer-based conjugates for tumor-targeting drug delivery |
CN103804693B (zh) | 2014-01-24 | 2016-03-09 | 中国科学院化学研究所 | 树枝状聚缩酮及其制备方法和应用 |
ES2861594T3 (es) | 2014-04-30 | 2021-10-06 | Univ Johns Hopkins | Composiciones de dendrímeros y su uso en el tratamiento de enfermedades del ojo |
US11918695B2 (en) * | 2014-05-09 | 2024-03-05 | Yale University | Topical formulation of hyperbranched polymer-coated particles |
CN103999853B (zh) | 2014-06-11 | 2015-07-22 | 中国农业大学 | 荧光树枝状纳米大分子在制备药物载体中的应用 |
US10918720B2 (en) | 2014-08-13 | 2021-02-16 | The Johns Hopkins University | Selective dendrimer delivery to brain tumors |
EP3368088B1 (en) | 2015-10-29 | 2023-06-07 | The Johns Hopkins University | Compositions and methods for treatment of peroxisomal disorders and leukodystrophies |
CN108883207A (zh) | 2016-02-08 | 2018-11-23 | 约翰霍普金斯大学 | 树状体-生物粘合剂聚合物水凝胶纳米胶水和其用途 |
-
2018
- 2018-11-13 AU AU2018365250A patent/AU2018365250B2/en active Active
- 2018-11-13 WO PCT/US2018/060795 patent/WO2019094952A1/en active Search and Examination
- 2018-11-13 CN CN201880086094.5A patent/CN111615528A/zh active Pending
- 2018-11-13 EP EP18812506.6A patent/EP3707193A1/en active Pending
- 2018-11-13 US US16/189,932 patent/US11918657B2/en active Active
- 2018-11-13 CA CA3082121A patent/CA3082121C/en active Active
- 2018-11-13 JP JP2020525944A patent/JP7383297B2/ja active Active
-
2020
- 2020-05-03 IL IL274390A patent/IL274390A/en unknown
-
2022
- 2022-08-24 AU AU2022221454A patent/AU2022221454A1/en active Pending
-
2023
- 2023-03-09 JP JP2023036541A patent/JP2023071973A/ja active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2017529325A (ja) | 2014-08-13 | 2017-10-05 | ザ・ジョンズ・ホプキンス・ユニバーシティー | 神経障害およびcns障害の処置におけるデンドリマー組成物および使用 |
JP2017525763A (ja) | 2014-08-22 | 2017-09-07 | インスティトゥート ディンベスティガシオ ビオメディカ デ ベルビッチェ(イディベル) | 感染症の予防および/または治療のための方法および試薬 |
WO2017074993A1 (en) | 2015-10-29 | 2017-05-04 | The Johns Hopkins University | Denderimer compositions and use in treatment of necrotizing enterocolitis and other gastrointestinal disorders |
Non-Patent Citations (4)
Title |
---|
Biomacromolecules,2012年,Vol.13, pp.3209-3219 |
Molecules,2016年,Vol.21, Article No.448 |
Polym. Chem.,2015年,Vol.6, pp.1436-1444 |
Polym. Chem.,2017年07月,Vol.8, pp.5354-5366 |
Also Published As
Publication number | Publication date |
---|---|
EP3707193A1 (en) | 2020-09-16 |
AU2022221454A1 (en) | 2022-09-22 |
AU2018365250B2 (en) | 2022-05-26 |
AU2018365250A1 (en) | 2020-06-11 |
WO2019094952A1 (en) | 2019-05-16 |
CA3082121C (en) | 2023-01-24 |
CN111615528A (zh) | 2020-09-01 |
CA3082121A1 (en) | 2019-05-16 |
JP2021502451A (ja) | 2021-01-28 |
US11918657B2 (en) | 2024-03-05 |
JP2023071973A (ja) | 2023-05-23 |
IL274390A (en) | 2020-06-30 |
US20190142964A1 (en) | 2019-05-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7383297B2 (ja) | デンドリマー送達システムおよびそれを使用する方法 | |
US10561673B2 (en) | Dendrimer based nanodevices for therapeutic and imaging purposes | |
Sharma et al. | Dense hydroxyl polyethylene glycol dendrimer targets activated glia in multiple CNS disorders | |
WO2016206540A1 (zh) | 一种八臂聚乙二醇衍生物、制备方法及其修饰的生物相关物质 | |
JP6366690B2 (ja) | 血液脳関門を通過するナノ粒子によって脳に治療薬および造影剤を送達する方法 | |
JP5349318B2 (ja) | ステロイド類の高分子結合体 | |
England et al. | Tumour regression and improved gastrointestinal tolerability from controlled release of SN-38 from novel polyoxazoline-modified dendrimers | |
DeRidder et al. | Dendrimer–tesaglitazar conjugate induces a phenotype shift of microglia and enhances β-amyloid phagocytosis | |
WO2019110067A1 (en) | Hybrid nanoparticle | |
Palan et al. | Dendrimers in the context of targeting central nervous system disorders | |
US20130210887A1 (en) | Dendrimers as non-viral vehicles for gene therapy | |
CA3232054A1 (en) | Dendrimer conjugates of small molecule biologics for intracellular delivery | |
WO2023196386A1 (en) | Dendrimer compositions for targeted delivery of therapeutics to neurons | |
Campos et al. | Dendrimers: A tool for advanced drug delivery | |
WO2024020597A1 (en) | Dendrimer-enabled targeted intracellular crispr/cas system delivery and gene editing | |
Guo | Cationic Amino Acid-Modified Camptothecin Prodrugs with Typical Helix Self-Assembly for Combination Cancer Therapy | |
KR20230163080A (ko) | 혈뇌 장벽 투과 이중가닥 올리고뉴클레오티드 구조체 및 이를 포함하는 신경학적 질환 예방 또는 치료용 조성물 | |
KR20150110974A (ko) | 표면작용기 조절을 통해 망막층 내로의 침투가 용이한 덴드리머 기반의 망막 질환 치료용 약물 전달체 | |
CN118159295A (zh) | 树枝状体缀合物及其使用方法 | |
WO2020232430A1 (en) | Methods of downregulating ccl20 genes for treatment of traumatic brain injuries | |
AU2010260349B2 (en) | Dendrimer based nanodevices for therapeutic and imaging purposes | |
Kambhampati | Dendrimer based nanotherapeutics for ocular drug delivery | |
residue agent Peptide | 8.1. 1.1 Biological Rationale |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20211115 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20211115 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20221209 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230309 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230512 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230809 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20231004 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20231031 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7383297 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |