TW202227069A - 用於治療緩解型多發性硬化症之方法 - Google Patents
用於治療緩解型多發性硬化症之方法 Download PDFInfo
- Publication number
- TW202227069A TW202227069A TW110130640A TW110130640A TW202227069A TW 202227069 A TW202227069 A TW 202227069A TW 110130640 A TW110130640 A TW 110130640A TW 110130640 A TW110130640 A TW 110130640A TW 202227069 A TW202227069 A TW 202227069A
- Authority
- TW
- Taiwan
- Prior art keywords
- compound
- cholesterol
- per day
- subject
- administered
- Prior art date
Links
- 201000006417 multiple sclerosis Diseases 0.000 title claims abstract description 63
- 238000000034 method Methods 0.000 title claims abstract description 58
- 229940125904 compound 1 Drugs 0.000 claims abstract description 118
- 150000003839 salts Chemical class 0.000 claims abstract description 26
- 239000003529 anticholesteremic agent Substances 0.000 claims abstract description 20
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 130
- 238000011282 treatment Methods 0.000 claims description 41
- 239000003814 drug Substances 0.000 claims description 25
- 229940079593 drug Drugs 0.000 claims description 22
- 150000001875 compounds Chemical class 0.000 claims description 8
- 229940125753 fibrate Drugs 0.000 claims description 8
- 108010072051 Glatiramer Acetate Proteins 0.000 claims description 7
- FHEAIOHRHQGZPC-KIWGSFCNSA-N acetic acid;(2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 FHEAIOHRHQGZPC-KIWGSFCNSA-N 0.000 claims description 7
- 229960003776 glatiramer acetate Drugs 0.000 claims description 7
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 4
- 102000003996 Interferon-beta Human genes 0.000 claims description 4
- 108090000467 Interferon-beta Proteins 0.000 claims description 4
- 229920000080 bile acid sequestrant Polymers 0.000 claims description 4
- 230000000977 initiatory effect Effects 0.000 claims description 4
- 229940122502 Cholesterol absorption inhibitor Drugs 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims 6
- 229940122392 PCSK9 inhibitor Drugs 0.000 claims 2
- 235000012000 cholesterol Nutrition 0.000 description 31
- 241000700159 Rattus Species 0.000 description 21
- 210000001519 tissue Anatomy 0.000 description 17
- -1 natal natalizumab Chemical compound 0.000 description 14
- 210000003594 spinal ganglia Anatomy 0.000 description 14
- 102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 description 13
- 108050001083 Sphingosine 1-phosphate receptors Proteins 0.000 description 13
- 208000016192 Demyelinating disease Diseases 0.000 description 12
- 206010012305 Demyelination Diseases 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 238000007901 in situ hybridization Methods 0.000 description 12
- 239000002609 medium Substances 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- 230000003902 lesion Effects 0.000 description 11
- 230000009467 reduction Effects 0.000 description 11
- 101000653757 Homo sapiens Sphingosine 1-phosphate receptor 4 Proteins 0.000 description 10
- 102000014150 Interferons Human genes 0.000 description 10
- 108010050904 Interferons Proteins 0.000 description 10
- 102100029803 Sphingosine 1-phosphate receptor 4 Human genes 0.000 description 10
- 210000000877 corpus callosum Anatomy 0.000 description 10
- UCTLRSWJYQTBFZ-UHFFFAOYSA-N Dehydrocholesterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)CCCC(C)C)CCC33)C)C3=CC=C21 UCTLRSWJYQTBFZ-UHFFFAOYSA-N 0.000 description 9
- 231100000673 dose–response relationship Toxicity 0.000 description 9
- 229940079322 interferon Drugs 0.000 description 9
- 210000004498 neuroglial cell Anatomy 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 9
- 210000003050 axon Anatomy 0.000 description 8
- 210000003169 central nervous system Anatomy 0.000 description 8
- 230000004069 differentiation Effects 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 230000023105 myelination Effects 0.000 description 8
- 210000000278 spinal cord Anatomy 0.000 description 8
- 238000009825 accumulation Methods 0.000 description 7
- 239000003613 bile acid Substances 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 208000007118 chronic progressive multiple sclerosis Diseases 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 7
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 102100040283 Peptidyl-prolyl cis-trans isomerase B Human genes 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- 230000001684 chronic effect Effects 0.000 description 6
- 229910052802 copper Inorganic materials 0.000 description 6
- 239000010949 copper Substances 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 208000004235 neutropenia Diseases 0.000 description 6
- 210000000440 neutrophil Anatomy 0.000 description 6
- 239000000902 placebo Substances 0.000 description 6
- 229940068196 placebo Drugs 0.000 description 6
- 201000008628 secondary progressive multiple sclerosis Diseases 0.000 description 6
- VKZRWSNIWNFCIQ-WDSKDSINSA-N (2s)-2-[2-[[(1s)-1,2-dicarboxyethyl]amino]ethylamino]butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NCCN[C@H](C(O)=O)CC(O)=O VKZRWSNIWNFCIQ-WDSKDSINSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 230000002518 glial effect Effects 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 210000004885 white matter Anatomy 0.000 description 5
- 241000282412 Homo Species 0.000 description 4
- 101000611202 Homo sapiens Peptidyl-prolyl cis-trans isomerase B Proteins 0.000 description 4
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 description 4
- 108010083644 Ribonucleases Proteins 0.000 description 4
- 102000006382 Ribonucleases Human genes 0.000 description 4
- LDCRTTXIJACKKU-ONEGZZNKSA-N dimethyl fumarate Chemical compound COC(=O)\C=C\C(=O)OC LDCRTTXIJACKKU-ONEGZZNKSA-N 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 238000012423 maintenance Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229950005751 ocrelizumab Drugs 0.000 description 4
- 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 4
- 229960002930 sirolimus Drugs 0.000 description 4
- 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 4
- 238000012360 testing method Methods 0.000 description 4
- RYCNUMLMNKHWPZ-SNVBAGLBSA-N 1-acetyl-sn-glycero-3-phosphocholine Chemical compound CC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C RYCNUMLMNKHWPZ-SNVBAGLBSA-N 0.000 description 3
- 102100036512 7-dehydrocholesterol reductase Human genes 0.000 description 3
- 229920001268 Cholestyramine Polymers 0.000 description 3
- 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 3
- 108010036949 Cyclosporine Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 101000928720 Homo sapiens 7-dehydrocholesterol reductase Proteins 0.000 description 3
- 238000011887 Necropsy Methods 0.000 description 3
- 108010025020 Nerve Growth Factor Proteins 0.000 description 3
- 102000015336 Nerve Growth Factor Human genes 0.000 description 3
- 208000018737 Parkinson disease Diseases 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000006696 biosynthetic metabolic pathway Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 229960001265 ciclosporin Drugs 0.000 description 3
- 238000003501 co-culture Methods 0.000 description 3
- 229960004419 dimethyl fumarate Drugs 0.000 description 3
- 229960000556 fingolimod Drugs 0.000 description 3
- KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical compound CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 210000004884 grey matter Anatomy 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 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 3
- 229960001156 mitoxantrone Drugs 0.000 description 3
- 229940053128 nerve growth factor Drugs 0.000 description 3
- 230000004770 neurodegeneration Effects 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- FYBHCRQFSFYWPY-UHFFFAOYSA-N purmorphamine Chemical compound C1CCCCC1N1C2=NC(OC=3C4=CC=CC=C4C=CC=3)=NC(NC=3C=CC(=CC=3)N3CCOCC3)=C2N=C1 FYBHCRQFSFYWPY-UHFFFAOYSA-N 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 238000012453 sprague-dawley rat model Methods 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 229950003937 tolonium Drugs 0.000 description 3
- HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- VTAKZNRDSPNOAU-UHFFFAOYSA-M 2-(chloromethyl)oxirane;hydron;prop-2-en-1-amine;n-prop-2-enyldecan-1-amine;trimethyl-[6-(prop-2-enylamino)hexyl]azanium;dichloride Chemical compound Cl.[Cl-].NCC=C.ClCC1CO1.CCCCCCCCCCNCC=C.C[N+](C)(C)CCCCCCNCC=C VTAKZNRDSPNOAU-UHFFFAOYSA-M 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 206010071068 Clinically isolated syndrome Diseases 0.000 description 2
- 229920002905 Colesevelam Polymers 0.000 description 2
- 229920002911 Colestipol Polymers 0.000 description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
- 229930105110 Cyclosporin A Natural products 0.000 description 2
- 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 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 2
- 102000015779 HDL Lipoproteins Human genes 0.000 description 2
- 108010010234 HDL Lipoproteins Proteins 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 208000023105 Huntington disease Diseases 0.000 description 2
- 208000035150 Hypercholesterolemia Diseases 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 102000006386 Myelin Proteins Human genes 0.000 description 2
- 108010083674 Myelin Proteins Proteins 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 229940127355 PCSK9 Inhibitors Drugs 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229960000548 alemtuzumab Drugs 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- HYHMLYSLQUKXKP-UHFFFAOYSA-N bempedoic acid Chemical compound OC(=O)C(C)(C)CCCCCC(O)CCCCCC(C)(C)C(O)=O HYHMLYSLQUKXKP-UHFFFAOYSA-N 0.000 description 2
- 229940096699 bile acid sequestrants Drugs 0.000 description 2
- 229960004436 budesonide Drugs 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 230000001906 cholesterol absorption Effects 0.000 description 2
- 229960002436 cladribine Drugs 0.000 description 2
- 238000011198 co-culture assay Methods 0.000 description 2
- 108010048032 cyclophilin B Proteins 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 229930182912 cyclosporin Natural products 0.000 description 2
- 229960002806 daclizumab Drugs 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- YIMYDTCOUQIDMT-SNAWJCMRSA-N diroximel fumarate Chemical compound COC(=O)\C=C\C(=O)OCCN1C(=O)CCC1=O YIMYDTCOUQIDMT-SNAWJCMRSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- ZVHRTJHLSYKEAK-UHFFFAOYSA-N ethyl 2-[5-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-2-oxo-3,4-dihydroquinolin-1-yl]acetate Chemical compound CCOC(=O)CN1C(=O)CCC2=C1C=CC=C2OC1=NC(=CC(CN)=C1)C(F)(F)F ZVHRTJHLSYKEAK-UHFFFAOYSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 229960000890 hydrocortisone Drugs 0.000 description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
- 238000010191 image analysis Methods 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- NKHAVTQWNUWKEO-NSCUHMNNSA-N monomethyl fumarate Chemical compound COC(=O)\C=C\C(O)=O NKHAVTQWNUWKEO-NSCUHMNNSA-N 0.000 description 2
- 238000002552 multiple reaction monitoring Methods 0.000 description 2
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 2
- 229960004866 mycophenolate mofetil Drugs 0.000 description 2
- 210000005012 myelin Anatomy 0.000 description 2
- 229960005027 natalizumab Drugs 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 210000003061 neural cell Anatomy 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 229960003512 nicotinic acid Drugs 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 108010044156 peptidyl-prolyl cis-trans isomerase b Proteins 0.000 description 2
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 229960002965 pravastatin Drugs 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000002203 pretreatment Methods 0.000 description 2
- 206010063401 primary progressive multiple sclerosis Diseases 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 2
- 229960004641 rituximab Drugs 0.000 description 2
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 229960001967 tacrolimus Drugs 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
- 229960000331 teriflunomide Drugs 0.000 description 2
- UTNUDOFZCWSZMS-YFHOEESVSA-N teriflunomide Chemical compound C\C(O)=C(/C#N)C(=O)NC1=CC=C(C(F)(F)F)C=C1 UTNUDOFZCWSZMS-YFHOEESVSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- 229940079023 tysabri Drugs 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
- ZMKGDQSIRSGUDJ-VSROPUKISA-N (3s,6s,9s,12r,15s,18s,21s,24s,30s,33s)-33-[(e,1r,2r)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-30-propyl-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,1 Chemical compound CCC[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 ZMKGDQSIRSGUDJ-VSROPUKISA-N 0.000 description 1
- KIHYPELVXPAIDH-HNSNBQBZSA-N 1-[[4-[(e)-n-[[4-cyclohexyl-3-(trifluoromethyl)phenyl]methoxy]-c-methylcarbonimidoyl]-2-ethylphenyl]methyl]azetidine-3-carboxylic acid Chemical compound CCC1=CC(C(\C)=N\OCC=2C=C(C(C3CCCCC3)=CC=2)C(F)(F)F)=CC=C1CN1CC(C(O)=O)C1 KIHYPELVXPAIDH-HNSNBQBZSA-N 0.000 description 1
- 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 1
- JWAZHODZSADEHB-UHFFFAOYSA-M 2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropanoate;2-hydroxyethyl(trimethyl)azanium Chemical compound C[N+](C)(C)CCO.C1=CC(OC(C)(C)C([O-])=O)=CC=C1C(=O)C1=CC=C(Cl)C=C1 JWAZHODZSADEHB-UHFFFAOYSA-M 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
- ILPUOPPYSQEBNJ-UHFFFAOYSA-N 2-methyl-2-phenoxypropanoic acid Chemical class OC(=O)C(C)(C)OC1=CC=CC=C1 ILPUOPPYSQEBNJ-UHFFFAOYSA-N 0.000 description 1
- TWQWRHIQRAZHPR-XNXCGYEVSA-N 3-[2-[(8s,9r,10s,11s,13s,14s,16r,17r)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethoxy]carbonylbenzenesulfonic acid Chemical compound O=C([C@]1(O)[C@@]2(C)C[C@H](O)[C@]3(F)[C@@]4(C)C=CC(=O)C=C4CC[C@H]3[C@@H]2C[C@H]1C)COC(=O)C1=CC=CC(S(O)(=O)=O)=C1 TWQWRHIQRAZHPR-XNXCGYEVSA-N 0.000 description 1
- SHBHYINHXNTBRP-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(2-methylsulfonylethyl)benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCCS(=O)(=O)C)C=CC=1 SHBHYINHXNTBRP-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
- XRVDGNKRPOAQTN-FQEVSTJZSA-N 5-[3-[(1s)-1-(2-hydroxyethylamino)-2,3-dihydro-1h-inden-4-yl]-1,2,4-oxadiazol-5-yl]-2-propan-2-yloxybenzonitrile Chemical compound C1=C(C#N)C(OC(C)C)=CC=C1C1=NC(C=2C=3CC[C@@H](C=3C=CC=2)NCCO)=NO1 XRVDGNKRPOAQTN-FQEVSTJZSA-N 0.000 description 1
- GWKQSBXDFHODNU-UQPSFNCESA-N 6z83r2hm9l Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)COC(=O)CCC(O)=O)[C@@]1(C)C[C@@H]2O GWKQSBXDFHODNU-UQPSFNCESA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- KUVIULQEHSCUHY-XYWKZLDCSA-N Beclometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O KUVIULQEHSCUHY-XYWKZLDCSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 1
- 101150013553 CD40 gene Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 1
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 1
- 208000032862 Clinical Deterioration Diseases 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- ITRJWOMZKQRYTA-RFZYENFJSA-N Cortisone acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)CC2=O ITRJWOMZKQRYTA-RFZYENFJSA-N 0.000 description 1
- DSRJIHMZAQEUJV-UHFFFAOYSA-N Cuprizon Chemical compound C1CCCCC1=NNC(=O)C(=O)NN=C1CCCCC1 DSRJIHMZAQEUJV-UHFFFAOYSA-N 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
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 102100025535 Delta(14)-sterol reductase TM7SF2 Human genes 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 206010014476 Elevated cholesterol Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- WJOHZNCJWYWUJD-IUGZLZTKSA-N Fluocinonide 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)COC(=O)C)[C@@]2(C)C[C@@H]1O WJOHZNCJWYWUJD-IUGZLZTKSA-N 0.000 description 1
- POPFMWWJOGLOIF-XWCQMRHXSA-N Flurandrenolide Chemical compound C1([C@@H](F)C2)=CC(=O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O POPFMWWJOGLOIF-XWCQMRHXSA-N 0.000 description 1
- 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 1
- MUQNGPZZQDCDFT-JNQJZLCISA-N Halcinonide Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CCl)[C@@]1(C)C[C@@H]2O MUQNGPZZQDCDFT-JNQJZLCISA-N 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101001056901 Homo sapiens Delta(14)-sterol reductase TM7SF2 Proteins 0.000 description 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
- 101001063392 Homo sapiens Lymphocyte function-associated antigen 3 Proteins 0.000 description 1
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 1
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
- 101100148568 Homo sapiens S1PR4 gene Proteins 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- HHZQLQREDATOBM-CODXZCKSSA-M Hydrocortisone Sodium Succinate Chemical compound [Na+].O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)COC(=O)CCC([O-])=O)[C@@H]4[C@@H]3CCC2=C1 HHZQLQREDATOBM-CODXZCKSSA-M 0.000 description 1
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 1
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108010008212 Integrin alpha4beta1 Proteins 0.000 description 1
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 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
- 102000007330 LDL Lipoproteins Human genes 0.000 description 1
- 108010007622 LDL Lipoproteins Proteins 0.000 description 1
- 102100030984 Lymphocyte function-associated antigen 3 Human genes 0.000 description 1
- 241000124008 Mammalia Species 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
- HZQDCMWJEBCWBR-UUOKFMHZSA-N Mizoribine Chemical compound OC1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 HZQDCMWJEBCWBR-UUOKFMHZSA-N 0.000 description 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 102000047918 Myelin Basic Human genes 0.000 description 1
- 101710107068 Myelin basic protein Proteins 0.000 description 1
- HIEKJRVYXXINKH-ADVKXBNGSA-N N1([C@H]2CC[C@H](C[C@H]2OC)/C=C(\C)[C@H]2OC(=O)[C@@H]3CCCCN3C(=O)C(=O)[C@]3(O)O[C@@H]([C@H](C[C@H]3C)OC)[C@@H](OC)C[C@@H](C)C/C(C)=C/[C@H](C(C[C@H](O)[C@H]2C)=O)CC)C=NN=N1 Chemical compound N1([C@H]2CC[C@H](C[C@H]2OC)/C=C(\C)[C@H]2OC(=O)[C@@H]3CCCCN3C(=O)C(=O)[C@]3(O)O[C@@H]([C@H](C[C@H]3C)OC)[C@@H](OC)C[C@@H](C)C/C(C)=C/[C@H](C(C[C@H](O)[C@H]2C)=O)CC)C=NN=N1 HIEKJRVYXXINKH-ADVKXBNGSA-N 0.000 description 1
- ZMKGDQSIRSGUDJ-UHFFFAOYSA-N NVa2 cyclosporine Natural products CCCC1NC(=O)C(C(O)C(C)CC=CC)N(C)C(=O)C(C(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(C)NC(=O)C(C)NC(=O)C(CC(C)C)N(C)C(=O)C(C(C)C)NC(=O)C(CC(C)C)N(C)C(=O)CN(C)C1=O ZMKGDQSIRSGUDJ-UHFFFAOYSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 229940126239 Nexletol Drugs 0.000 description 1
- 108700018419 Niemann-Pick C1 Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 1
- 108091008606 PDGF receptors Proteins 0.000 description 1
- 101150057744 PDGFA gene Proteins 0.000 description 1
- 101150038994 PDGFRA gene Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 1
- LRJOMUJRLNCICJ-JZYPGELDSA-N Prednisolone acetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O LRJOMUJRLNCICJ-JZYPGELDSA-N 0.000 description 1
- 102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 description 1
- 101710180553 Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 230000006819 RNA synthesis Effects 0.000 description 1
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 101150078138 S1PR4 gene Proteins 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- 241000282887 Suidae Species 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- XGMPVBXKDAHORN-RBWIMXSLSA-N Triamcinolone diacetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](OC(C)=O)[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O XGMPVBXKDAHORN-RBWIMXSLSA-N 0.000 description 1
- TZIZWYVVGLXXFV-FLRHRWPCSA-N Triamcinolone hexacetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)COC(=O)CC(C)(C)C)[C@@]1(C)C[C@@H]2O TZIZWYVVGLXXFV-FLRHRWPCSA-N 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- FPVRUILUEYSIMD-RPRRAYFGSA-N [(8s,9r,10s,11s,13s,14s,16r,17r)-9-fluoro-11-hydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl] acetate 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)(OC(C)=O)[C@@]1(C)C[C@@H]2O FPVRUILUEYSIMD-RPRRAYFGSA-N 0.000 description 1
- WBNNIURTBZHJTI-WDCKKOMHSA-N [2-[(8s,9s,10r,11s,13s,14s,17r)-11,17-dihydroxy-10,13-dimethyl-3-oxo-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl] dihydrogen phosphate;2-[(2-propan-2-ylphenoxy)methyl]-4,5-dihydro-1h-imidazole Chemical compound CC(C)C1=CC=CC=C1OCC1=NCCN1.O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)COP(O)(O)=O)[C@@H]4[C@@H]3CCC2=C1 WBNNIURTBZHJTI-WDCKKOMHSA-N 0.000 description 1
- DNSAKUGJOSFARZ-FOMYWIRZSA-N [2-[(8s,9s,10r,11s,13s,14s,17r)-11,17-dihydroxy-10,13-dimethyl-3-oxo-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl] hexanoate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)CCCCC)(O)[C@@]1(C)C[C@@H]2O DNSAKUGJOSFARZ-FOMYWIRZSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 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 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 229960004229 alclometasone dipropionate Drugs 0.000 description 1
- DJHCCTTVDRAMEH-DUUJBDRPSA-N alclometasone dipropionate Chemical compound C([C@H]1Cl)C2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O DJHCCTTVDRAMEH-DUUJBDRPSA-N 0.000 description 1
- 229960004539 alirocumab Drugs 0.000 description 1
- 229940027030 altoprev Drugs 0.000 description 1
- 229960003099 amcinonide Drugs 0.000 description 1
- ILKJAFIWWBXGDU-MOGDOJJUSA-N amcinonide Chemical compound O([C@@]1([C@H](O2)C[C@@H]3[C@@]1(C[C@H](O)[C@]1(F)[C@@]4(C)C=CC(=O)C=C4CC[C@H]13)C)C(=O)COC(=O)C)C12CCCC1 ILKJAFIWWBXGDU-MOGDOJJUSA-N 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
- 210000003484 anatomy Anatomy 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 238000011861 anti-inflammatory therapy Methods 0.000 description 1
- 230000002502 anti-myelin effect Effects 0.000 description 1
- 239000002787 antisense oligonuctleotide Substances 0.000 description 1
- 108010054176 apotransferrin Proteins 0.000 description 1
- ZDQSOHOQTUFQEM-PKUCKEGBSA-N ascomycin Chemical compound C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C\C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CC)=C\[C@@H]1CC[C@@H](O)[C@H](OC)C1 ZDQSOHOQTUFQEM-PKUCKEGBSA-N 0.000 description 1
- ZDQSOHOQTUFQEM-XCXYXIJFSA-N ascomycin Natural products CC[C@H]1C=C(C)C[C@@H](C)C[C@@H](OC)[C@H]2O[C@@](O)([C@@H](C)C[C@H]2OC)C(=O)C(=O)N3CCCC[C@@H]3C(=O)O[C@H]([C@H](C)[C@@H](O)CC1=O)C(=C[C@@H]4CC[C@@H](O)[C@H](C4)OC)C ZDQSOHOQTUFQEM-XCXYXIJFSA-N 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- FQCKMBLVYCEXJB-MNSAWQCASA-L atorvastatin calcium Chemical compound [Ca+2].C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1.C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 FQCKMBLVYCEXJB-MNSAWQCASA-L 0.000 description 1
- 230000003376 axonal effect Effects 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 229960004669 basiliximab Drugs 0.000 description 1
- 229950000210 beclometasone dipropionate Drugs 0.000 description 1
- 229950002974 bempedoic acid Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000003339 best practice Methods 0.000 description 1
- 229960002537 betamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone 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-DVTGEIKXSA-N 0.000 description 1
- 229960001102 betamethasone dipropionate Drugs 0.000 description 1
- CIWBQSYVNNPZIQ-XYWKZLDCSA-N betamethasone dipropionate 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)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O CIWBQSYVNNPZIQ-XYWKZLDCSA-N 0.000 description 1
- 229960005354 betamethasone sodium phosphate Drugs 0.000 description 1
- PLCQGRYPOISRTQ-LWCNAHDDSA-L betamethasone sodium phosphate Chemical compound [Na+].[Na+].C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COP([O-])([O-])=O)(O)[C@@]1(C)C[C@@H]2O PLCQGRYPOISRTQ-LWCNAHDDSA-L 0.000 description 1
- 229960004311 betamethasone valerate Drugs 0.000 description 1
- SNHRLVCMMWUAJD-SUYDQAKGSA-N betamethasone valerate 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)(OC(=O)CCCC)[C@@]1(C)C[C@@H]2O SNHRLVCMMWUAJD-SUYDQAKGSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960004703 clobetasol propionate Drugs 0.000 description 1
- CBGUOGMQLZIXBE-XGQKBEPLSA-N clobetasol propionate 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)CCl)(OC(=O)CC)[C@@]1(C)C[C@@H]2O CBGUOGMQLZIXBE-XGQKBEPLSA-N 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 229960001152 colesevelam Drugs 0.000 description 1
- 229940097479 colestid Drugs 0.000 description 1
- 229960002604 colestipol Drugs 0.000 description 1
- GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- BMCQMVFGOVHVNG-TUFAYURCSA-N cortisol 17-butyrate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)CO)(OC(=O)CCC)[C@@]1(C)C[C@@H]2O BMCQMVFGOVHVNG-TUFAYURCSA-N 0.000 description 1
- ALEXXDVDDISNDU-JZYPGELDSA-N cortisol 21-acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O ALEXXDVDDISNDU-JZYPGELDSA-N 0.000 description 1
- 229960003290 cortisone acetate Drugs 0.000 description 1
- 229960003840 cortivazol Drugs 0.000 description 1
- RKHQGWMMUURILY-UHRZLXHJSA-N cortivazol Chemical compound C([C@H]1[C@@H]2C[C@H]([C@]([C@@]2(C)C[C@H](O)[C@@H]1[C@@]1(C)C2)(O)C(=O)COC(C)=O)C)=C(C)C1=CC1=C2C=NN1C1=CC=CC=C1 RKHQGWMMUURILY-UHRZLXHJSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 108010019249 cyclosporin G Proteins 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000013135 deep learning Methods 0.000 description 1
- 229960003662 desonide Drugs 0.000 description 1
- WBGKWQHBNHJJPZ-LECWWXJVSA-N desonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O WBGKWQHBNHJJPZ-LECWWXJVSA-N 0.000 description 1
- 229960002593 desoximetasone Drugs 0.000 description 1
- VWVSBHGCDBMOOT-IIEHVVJPSA-N desoximetasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@H](C(=O)CO)[C@@]1(C)C[C@@H]2O VWVSBHGCDBMOOT-IIEHVVJPSA-N 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
- 229960003657 dexamethasone acetate Drugs 0.000 description 1
- 229960000524 dexamethasone isonicotinate Drugs 0.000 description 1
- 229960004833 dexamethasone phosphate Drugs 0.000 description 1
- VQODGRNSFPNSQE-CXSFZGCWSA-N dexamethasone phosphate 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)COP(O)(O)=O)(O)[C@@]1(C)C[C@@H]2O VQODGRNSFPNSQE-CXSFZGCWSA-N 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000002598 diffusion tensor imaging Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
- 229950008803 diroximel fumarate Drugs 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 238000011979 disease modifying therapy Methods 0.000 description 1
- BVTBRVFYZUCAKH-UHFFFAOYSA-L disodium selenite Chemical compound [Na+].[Na+].[O-][Se]([O-])=O BVTBRVFYZUCAKH-UHFFFAOYSA-L 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 239000003822 epoxy resin Substances 0.000 description 1
- 229960002027 evolocumab Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229960000815 ezetimibe Drugs 0.000 description 1
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 229960002297 fenofibrate Drugs 0.000 description 1
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 229940103386 fibricor Drugs 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- SYWHXTATXSMDSB-GSLJADNHSA-N fludrocortisone acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O SYWHXTATXSMDSB-GSLJADNHSA-N 0.000 description 1
- 229960004511 fludroxycortide Drugs 0.000 description 1
- 229940042902 flumethasone pivalate Drugs 0.000 description 1
- JWRMHDSINXPDHB-OJAGFMMFSA-N flumethasone pivalate 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](C)[C@@](C(=O)COC(=O)C(C)(C)C)(O)[C@@]2(C)C[C@@H]1O JWRMHDSINXPDHB-OJAGFMMFSA-N 0.000 description 1
- 229960000676 flunisolide Drugs 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
- 229960000785 fluocinonide Drugs 0.000 description 1
- 229960003973 fluocortolone Drugs 0.000 description 1
- GAKMQHDJQHZUTJ-ULHLPKEOSA-N fluocortolone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@@H](C)[C@H](C(=O)CO)[C@@]2(C)C[C@@H]1O GAKMQHDJQHZUTJ-ULHLPKEOSA-N 0.000 description 1
- 229960003336 fluorocortisol acetate Drugs 0.000 description 1
- 229960001048 fluorometholone Drugs 0.000 description 1
- FAOZLTXFLGPHNG-KNAQIMQKSA-N fluorometholone Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@]2(F)[C@@H](O)C[C@]2(C)[C@@](O)(C(C)=O)CC[C@H]21 FAOZLTXFLGPHNG-KNAQIMQKSA-N 0.000 description 1
- 229960002650 fluprednidene acetate Drugs 0.000 description 1
- DEFOZIFYUBUHHU-IYQKUMFPSA-N fluprednidene acetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1CC(=C)[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O DEFOZIFYUBUHHU-IYQKUMFPSA-N 0.000 description 1
- 229960000289 fluticasone propionate Drugs 0.000 description 1
- WMWTYOKRWGGJOA-CENSZEJFSA-N fluticasone propionate 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](C)[C@@](C(=O)SCF)(OC(=O)CC)[C@@]2(C)C[C@@H]1O WMWTYOKRWGGJOA-CENSZEJFSA-N 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 229940050411 fumarate Drugs 0.000 description 1
- NKHAVTQWNUWKEO-UHFFFAOYSA-N fumaric acid monomethyl ester Natural products COC(=O)C=CC(O)=O NKHAVTQWNUWKEO-UHFFFAOYSA-N 0.000 description 1
- 229960005277 gemcitabine 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
- 229960003627 gemfibrozil Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 229960002383 halcinonide Drugs 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 229960001067 hydrocortisone acetate Drugs 0.000 description 1
- 229960001524 hydrocortisone butyrate Drugs 0.000 description 1
- 229950006240 hydrocortisone succinate Drugs 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 229940124622 immune-modulator drug Drugs 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 description 1
- 229960000681 leflunomide Drugs 0.000 description 1
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229940002661 lipitor Drugs 0.000 description 1
- 229940092923 livalo Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229940063720 lopid Drugs 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000005415 magnetization Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229960001924 melphalan 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
- 210000002418 meninge Anatomy 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
- 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
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- OJLOPKGSLYJEMD-URPKTTJQSA-N methyl 7-[(1r,2r,3r)-3-hydroxy-2-[(1e)-4-hydroxy-4-methyloct-1-en-1-yl]-5-oxocyclopentyl]heptanoate Chemical compound CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC OJLOPKGSLYJEMD-URPKTTJQSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229960004584 methylprednisolone Drugs 0.000 description 1
- 229960001293 methylprednisolone acetate Drugs 0.000 description 1
- PLBHSZGDDKCEHR-LFYFAGGJSA-N methylprednisolone acetate Chemical compound 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(C)=O)CC[C@H]21 PLBHSZGDDKCEHR-LFYFAGGJSA-N 0.000 description 1
- IMBXEJJVJRTNOW-XYMSELFBSA-N methylprednisolone succinate Chemical compound 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 IMBXEJJVJRTNOW-XYMSELFBSA-N 0.000 description 1
- 229950009831 methylprednisolone succinate Drugs 0.000 description 1
- 230000002025 microglial effect Effects 0.000 description 1
- 229960005249 misoprostol Drugs 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 229950000844 mizoribine Drugs 0.000 description 1
- 229940005650 monomethyl fumarate Drugs 0.000 description 1
- 229960003816 muromonab-cd3 Drugs 0.000 description 1
- 210000003007 myelin sheath Anatomy 0.000 description 1
- GACQNVJDWUAPFY-UHFFFAOYSA-N n'-[2-[2-(2-aminoethylamino)ethylamino]ethyl]ethane-1,2-diamine;hydrochloride Chemical compound Cl.NCCNCCNCCNCCN GACQNVJDWUAPFY-UHFFFAOYSA-N 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 238000010984 neurological examination Methods 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 229950008141 ozanimod Drugs 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 229960002797 pitavastatin Drugs 0.000 description 1
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 1
- RHGYHLPFVJEAOC-FFNUKLMVSA-L pitavastatin calcium Chemical compound [Ca+2].[O-]C(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1.[O-]C(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 RHGYHLPFVJEAOC-FFNUKLMVSA-L 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920000647 polyepoxide Polymers 0.000 description 1
- 229940089484 pravachol Drugs 0.000 description 1
- 229960001297 prednazoline Drugs 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 229960002800 prednisolone acetate Drugs 0.000 description 1
- JDOZJEUDSLGTLU-VWUMJDOOSA-N prednisolone phosphate Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)COP(O)(O)=O)[C@@H]4[C@@H]3CCC2=C1 JDOZJEUDSLGTLU-VWUMJDOOSA-N 0.000 description 1
- 229960002943 prednisolone sodium phosphate Drugs 0.000 description 1
- 229950004954 prednisolone sulfobenzoate Drugs 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 229960001917 prednylidene Drugs 0.000 description 1
- WSVOMANDJDYYEY-CWNVBEKCSA-N prednylidene Chemical group O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](C(=C)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 WSVOMANDJDYYEY-CWNVBEKCSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 229940096203 prevalite Drugs 0.000 description 1
- 229960003912 probucol Drugs 0.000 description 1
- FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 210000004129 prosencephalon Anatomy 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 description 1
- 238000001303 quality assessment method Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 229940073095 questran Drugs 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- 229960000672 rosuvastatin Drugs 0.000 description 1
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 1
- 239000002412 selectin antagonist Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- 229950005693 siponimod Drugs 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229960001471 sodium selenite Drugs 0.000 description 1
- 235000015921 sodium selenite Nutrition 0.000 description 1
- 239000011781 sodium selenite Substances 0.000 description 1
- ZGGHKIMDNBDHJB-CALJPSDSSA-M sodium;(e)-7-[3-(4-fluorophenyl)-1-propan-2-ylindol-2-yl]-3,5-dihydroxyhept-6-enoate Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\C(O)CC(O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-CALJPSDSSA-M 0.000 description 1
- RWFZSORKWFPGNE-VDYYWZOJSA-M sodium;3-[2-[(8s,9s,10r,11s,13s,14s,17r)-11,17-dihydroxy-10,13-dimethyl-3-oxo-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-17-yl]-2-oxoethoxy]carbonylbenzenesulfonate Chemical compound [Na+].O=C([C@@]1(O)CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)[C@@H](O)C[C@@]21C)COC(=O)C1=CC=CC(S([O-])(=O)=O)=C1 RWFZSORKWFPGNE-VDYYWZOJSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000000273 spinal nerve root Anatomy 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 229940121136 tecfidera Drugs 0.000 description 1
- 229960003433 thalidomide Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- FYOWZTWVYZOZSI-UHFFFAOYSA-N thiourea dioxide Chemical compound NC(=N)S(O)=O FYOWZTWVYZOZSI-UHFFFAOYSA-N 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- BISFDZNIUZIKJD-XDANTLIUSA-N tixocortol pivalate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)CSC(=O)C(C)(C)C)(O)[C@@]1(C)C[C@@H]2O BISFDZNIUZIKJD-XDANTLIUSA-N 0.000 description 1
- 229960003114 tixocortol pivalate Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- GUYPYYARYIIWJZ-CYEPYHPTSA-N triamcinolone benetonide Chemical compound O=C([C@]12[C@H](OC(C)(C)O1)C[C@@H]1[C@@]2(C[C@H](O)[C@]2(F)[C@@]3(C)C=CC(=O)C=C3CC[C@H]21)C)COC(=O)C(C)CNC(=O)C1=CC=CC=C1 GUYPYYARYIIWJZ-CYEPYHPTSA-N 0.000 description 1
- 229950006782 triamcinolone benetonide Drugs 0.000 description 1
- 229960004320 triamcinolone diacetate Drugs 0.000 description 1
- 229960004221 triamcinolone hexacetonide Drugs 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229950004593 ublituximab Drugs 0.000 description 1
- 238000011870 unpaired t-test Methods 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000004218 vascular function Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229940111503 welchol Drugs 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/451—Non condensed piperidines, e.g. piperocaine having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/02—Peptides of undefined number of amino acids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
- A61K38/215—IFN-beta
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/92—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving lipids, e.g. cholesterol, lipoproteins, or their receptors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Hematology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Biophysics (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Microbiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202063067727P | 2020-08-19 | 2020-08-19 | |
| US63/067,727 | 2020-08-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW202227069A true TW202227069A (zh) | 2022-07-16 |
Family
ID=77693630
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW110130640A TW202227069A (zh) | 2020-08-19 | 2021-08-19 | 用於治療緩解型多發性硬化症之方法 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20230390270A1 (https=) |
| EP (1) | EP4199927A1 (https=) |
| JP (1) | JP2023538065A (https=) |
| CN (1) | CN116096421A (https=) |
| TW (1) | TW202227069A (https=) |
| WO (1) | WO2022040369A1 (https=) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12472171B2 (en) * | 2020-08-19 | 2025-11-18 | Biogen Ma Inc. | Methods for treating hypercholesterolemia |
| WO2023154925A1 (en) * | 2022-02-14 | 2023-08-17 | Genetic Innovations, Inc. | Medical spectroscopy and imaging analysis |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA034451B1 (ru) * | 2011-02-07 | 2020-02-10 | Байоджен Ма Инк. | Модуляторы s1p |
| JP6324380B2 (ja) * | 2012-07-27 | 2018-05-16 | バイオジェン・エムエイ・インコーポレイテッドＢｉｏｇｅｎ ＭＡ Ｉｎｃ． | Ｓ１ｐ調節剤および／またはａｔｘ調節剤である化合物 |
| CA2899322A1 (en) * | 2013-01-29 | 2014-08-07 | Biogen Ma Inc. | S1p modulating agents |
-
2021
- 2021-08-19 US US18/021,643 patent/US20230390270A1/en active Pending
- 2021-08-19 CN CN202180051098.1A patent/CN116096421A/zh active Pending
- 2021-08-19 EP EP21766792.2A patent/EP4199927A1/en active Pending
- 2021-08-19 WO PCT/US2021/046589 patent/WO2022040369A1/en not_active Ceased
- 2021-08-19 TW TW110130640A patent/TW202227069A/zh unknown
- 2021-08-19 JP JP2023511903A patent/JP2023538065A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2022040369A8 (en) | 2022-04-14 |
| US20230390270A1 (en) | 2023-12-07 |
| WO2022040369A1 (en) | 2022-02-24 |
| CN116096421A (zh) | 2023-05-09 |
| EP4199927A1 (en) | 2023-06-28 |
| JP2023538065A (ja) | 2023-09-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7734427B2 (ja) | 神経由来エクソソーム中の核酸の検出方法および分析方法 | |
| EP3080602B1 (en) | Treating neurodegenerative disease | |
| US12219938B2 (en) | Mouse model of alcohol-induced liver cancer | |
| TW202227069A (zh) | 用於治療緩解型多發性硬化症之方法 | |
| Li et al. | Lipocalin-2-mediated insufficient oligodendrocyte progenitor cell remyelination for white matter injury after subarachnoid hemorrhage via SCL22A17 receptor/early growth response protein 1 signaling | |
| Guo et al. | SHED-derived exosomes attenuate trigeminal neuralgia after CCI of the infraorbital nerve in mice via the miR-24-3p/IL-1R1/p-p38 MAPK pathway | |
| Ahrendsen et al. | The protein tyrosine phosphatase Shp2 regulates oligodendrocyte differentiation and early myelination and contributes to timely remyelination | |
| Liu et al. | Aging alters the effect of adiponectin receptor signaling on bone marrow‐derived mesenchymal stem cells | |
| JP2025535729A (ja) | 神経変性疾患を評価及び治療するためのタンパク質マーカー | |
| KR20250070087A (ko) | 신경변성 질병과 관련된 신경변성의 감소 방법 | |
| Guan et al. | Bone-Derived Factors: Regulating Brain and Treating Alzheimer’s Disease | |
| EP4407315A1 (en) | Diagnosis and treatment of neurogenic heterotopic ossification | |
| CN114990204B (zh) | 一种trex1基因变异引起的疾病的治疗靶点及其应用 | |
| Wang et al. | Lycium barbarum polysaccharide improves the cognitive deficits in APP/PS1 mice of Alzheimer’s disease via modulating the microbiota-gut-brain axis | |
| Wang et al. | LncRNA Mir155hg Knockdown Attenuates Inflammation and Cognitive Impairment through regulating the NF-κΒ signaling pathway in a Rat Model of Status Epilepticus | |
| Lu et al. | TREM2 Downregulation Disrupts Microglial Function and Synaptic Pruning Through RA/RARα Signaling: Mechanisms Underlying Autism‐Like Behaviors | |
| Carcak et al. | REPARIXIN AS A POTENTIAL ANTI-EPILEPTOGENIC AGENT: MODULATION OF CXCL1-CXCR1/2 AXIS AND SEIZURE ACTIVITY IN KINDLING MODEL OF TEMPORAL LOBE EPILEPSY | |
| Krull et al. | Findings from transcriptomics and immunohistochemistry reveal an autoimmune disease targeting brainstem inhibitory interneurons in bovine spastic paresis | |
| Kamel et al. | STUDIES ON ADIPOSE–DERIVED STEM CELLS AS TREATMENT OF MUSCULAR DYSTROPHY INDUCED IN RATS | |
| Chen | Profiling the Molecular Signatures of Astrocytes in Synucleinopathy and Therapeutic Targeting in Aging | |
| Kambey et al. | Synergistic effect of combined GDNF and Amodiaquine attenuates behavioral deficits and protect dopaminergic neurons of Parkinson’s disease animal model through tyrosine kinase Ret receptor | |
| van Wageningen et al. | Distinct gene expression profiles in leukocortical demyelinated white and grey matter areas of Multiple Sclerosis patients | |
| WO2023079079A1 (en) | Methods for treating multiple sclerosis | |
| CN121489954A (zh) | Ogg1小分子激动剂在制备用于治疗肝脏炎症性疾病的药物中的应用 | |
| Kertser | Regulation of the blood-cerebrospinal fluid barrier as a gateway for leukocyte trafficking in physiology and pathology |