TW201436790A - 經氘取代之反丁烯二酸酯衍生物類 - Google Patents

Info

Publication number

TW201436790A

TW201436790A TW102147528A TW102147528A TW201436790A TW 201436790 A TW201436790 A TW 201436790A TW 102147528 A TW102147528 A TW 102147528A TW 102147528 A TW102147528 A TW 102147528A TW 201436790 A TW201436790 A TW 201436790A

Authority

TW

Taiwan

Prior art keywords

disease

compound

syndrome

acute

administered

Prior art date

2012-12-21

Links

• Espacenet
• Global Dossier
• Discuss

• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 title claims description 32
• 229910052805 deuterium Inorganic materials 0.000 title claims description 19
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 title claims description 14
• 150000001875 compounds Chemical class 0.000 claims abstract description 132
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 49
• 201000010099 disease Diseases 0.000 claims abstract description 45
• 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 32
• 230000004770 neurodegeneration Effects 0.000 claims abstract description 25
• 238000011282 treatment Methods 0.000 claims abstract description 24
• 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 19
• 150000003839 salts Chemical class 0.000 claims abstract description 17
• 208000023105 Huntington disease Diseases 0.000 claims abstract description 16
• 208000018737 Parkinson disease Diseases 0.000 claims abstract description 16
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims abstract description 16
• 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 12
• 238000011321 prophylaxis Methods 0.000 claims abstract 2
• LDCRTTXIJACKKU-ONEGZZNKSA-N dimethyl fumarate Chemical compound COC(=O)\C=C\C(=O)OC LDCRTTXIJACKKU-ONEGZZNKSA-N 0.000 claims description 58
• 229960004419 dimethyl fumarate Drugs 0.000 claims description 53
• -1 dimethyl methacrylate Chemical compound 0.000 claims description 41
• 101000588302 Homo sapiens Nuclear factor erythroid 2-related factor 2 Proteins 0.000 claims description 39
• 102100031701 Nuclear factor erythroid 2-related factor 2 Human genes 0.000 claims description 39
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 29
• 210000004027 cell Anatomy 0.000 claims description 24
• 239000003814 drug Substances 0.000 claims description 24
• VZCYOOQTPOCHFL-FBBQFRKLSA-N (e)-2,3-dideuteriobut-2-enedioic acid Chemical compound OC(=O)C(/[2H])=C(\[2H])C(O)=O VZCYOOQTPOCHFL-FBBQFRKLSA-N 0.000 claims description 21
• 125000001931 aliphatic group Chemical group 0.000 claims description 19
• 229910052739 hydrogen Inorganic materials 0.000 claims description 19
• 239000001257 hydrogen Substances 0.000 claims description 19
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 19
• 239000001530 fumaric acid Substances 0.000 claims description 18
• 229910052757 nitrogen Inorganic materials 0.000 claims description 17
• 229920006395 saturated elastomer Polymers 0.000 claims description 14
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
• 208000029078 coronary artery disease Diseases 0.000 claims description 13
• OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 claims description 13
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 12
• 230000001154 acute effect Effects 0.000 claims description 12
• 125000000623 heterocyclic group Chemical group 0.000 claims description 12
• 230000037361 pathway Effects 0.000 claims description 12
• 230000000750 progressive effect Effects 0.000 claims description 12
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
• 201000002491 encephalomyelitis Diseases 0.000 claims description 11
• 125000005842 heteroatom Chemical group 0.000 claims description 11
• 229910052760 oxygen Inorganic materials 0.000 claims description 11
• 239000001301 oxygen Chemical group 0.000 claims description 11
• 208000011580 syndromic disease Diseases 0.000 claims description 11
• 208000016192 Demyelinating disease Diseases 0.000 claims description 10
• 229910052717 sulfur Chemical group 0.000 claims description 10
• 239000011593 sulfur Chemical group 0.000 claims description 10
• 230000001684 chronic effect Effects 0.000 claims description 9
• 150000002148 esters Chemical class 0.000 claims description 9
• 230000002757 inflammatory effect Effects 0.000 claims description 9
• 206010012305 Demyelination Diseases 0.000 claims description 8
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
• 206010028980 Neoplasm Diseases 0.000 claims description 8
• 201000011040 acute kidney failure Diseases 0.000 claims description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
• 238000002360 preparation method Methods 0.000 claims description 8
• 206010036807 progressive multifocal leukoencephalopathy Diseases 0.000 claims description 8
• 206010028570 Myelopathy Diseases 0.000 claims description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
• 201000004624 Dermatitis Diseases 0.000 claims description 6
• 239000002253 acid Substances 0.000 claims description 6
• 206010003246 arthritis Diseases 0.000 claims description 6
• 208000006673 asthma Diseases 0.000 claims description 6
• 206010012601 diabetes mellitus Diseases 0.000 claims description 6
• 208000024908 graft versus host disease Diseases 0.000 claims description 6
• 125000002950 monocyclic group Chemical group 0.000 claims description 6
• 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 5
• 201000002169 Mitochondrial myopathy Diseases 0.000 claims description 5
• 208000003435 Optic Neuritis Diseases 0.000 claims description 5
• 206010039491 Sarcoma Diseases 0.000 claims description 5
• 206010039710 Scleroderma Diseases 0.000 claims description 5
• 208000029033 Spinal Cord disease Diseases 0.000 claims description 5
• 208000006011 Stroke Diseases 0.000 claims description 5
• 201000011510 cancer Diseases 0.000 claims description 5
• 150000001975 deuterium Chemical group 0.000 claims description 5
• 208000006454 hepatitis Diseases 0.000 claims description 5
• 208000023692 inborn mitochondrial myopathy Diseases 0.000 claims description 5
• 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 5
• 210000004185 liver Anatomy 0.000 claims description 5
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 5
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
• 230000002685 pulmonary effect Effects 0.000 claims description 5
• 230000005855 radiation Effects 0.000 claims description 5
• 208000009174 transverse myelitis Diseases 0.000 claims description 5
• 210000004885 white matter Anatomy 0.000 claims description 5
• 208000009304 Acute Kidney Injury Diseases 0.000 claims description 4
• 208000007848 Alcoholism Diseases 0.000 claims description 4
• 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 4
• 206010003497 Asphyxia Diseases 0.000 claims description 4
• 206010008025 Cerebellar ataxia Diseases 0.000 claims description 4
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
• 206010012289 Dementia Diseases 0.000 claims description 4
• 208000004986 Diffuse Cerebral Sclerosis of Schilder Diseases 0.000 claims description 4
• 208000034800 Leukoencephalopathies Diseases 0.000 claims description 4
• 206010033799 Paralysis Diseases 0.000 claims description 4
• 208000031845 Pernicious anaemia Diseases 0.000 claims description 4
• 208000033626 Renal failure acute Diseases 0.000 claims description 4
• 208000017442 Retinal disease Diseases 0.000 claims description 4
• 206010038923 Retinopathy Diseases 0.000 claims description 4
• 206010040047 Sepsis Diseases 0.000 claims description 4
• 206010040070 Septic Shock Diseases 0.000 claims description 4
• 208000032851 Subarachnoid Hemorrhage Diseases 0.000 claims description 4
• IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 claims description 4
• 206010047115 Vasculitis Diseases 0.000 claims description 4
• 206010069351 acute lung injury Diseases 0.000 claims description 4
• 201000007930 alcohol dependence Diseases 0.000 claims description 4
• 210000003678 bronchial smooth muscle cell Anatomy 0.000 claims description 4
• 206010006475 bronchopulmonary dysplasia Diseases 0.000 claims description 4
• 201000005795 chronic inflammatory demyelinating polyneuritis Diseases 0.000 claims description 4
• 208000019425 cirrhosis of liver Diseases 0.000 claims description 4
• 230000007850 degeneration Effects 0.000 claims description 4
• 206010061811 demyelinating polyneuropathy Diseases 0.000 claims description 4
• 239000000835 fiber Substances 0.000 claims description 4
• 201000005206 focal segmental glomerulosclerosis Diseases 0.000 claims description 4
• 231100000854 focal segmental glomerulosclerosis Toxicity 0.000 claims description 4
• 231100000283 hepatitis Toxicity 0.000 claims description 4
• 150000002431 hydrogen Chemical class 0.000 claims description 4
• 210000003205 muscle Anatomy 0.000 claims description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
• 201000008482 osteoarthritis Diseases 0.000 claims description 4
• 201000002793 renal fibrosis Diseases 0.000 claims description 4
• 230000004044 response Effects 0.000 claims description 4
• 208000037803 restenosis Diseases 0.000 claims description 4
• 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 4
• 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 3
• 208000033222 Biliary cirrhosis primary Diseases 0.000 claims description 3
• 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 3
• 208000018522 Gastrointestinal disease Diseases 0.000 claims description 3
• 208000035895 Guillain-Barré syndrome Diseases 0.000 claims description 3
• 206010019799 Hepatitis viral Diseases 0.000 claims description 3
• 241000714260 Human T-lymphotropic virus 1 Species 0.000 claims description 3
• 206010020751 Hypersensitivity Diseases 0.000 claims description 3
• 201000010743 Lambert-Eaton myasthenic syndrome Diseases 0.000 claims description 3
• 206010049567 Miller Fisher syndrome Diseases 0.000 claims description 3
• 208000021642 Muscular disease Diseases 0.000 claims description 3
• 206010028424 Myasthenic syndrome Diseases 0.000 claims description 3
• 201000009623 Myopathy Diseases 0.000 claims description 3
• 208000012654 Primary biliary cholangitis Diseases 0.000 claims description 3
• 208000006311 Pyoderma Diseases 0.000 claims description 3
• 208000018756 Variant Creutzfeldt-Jakob disease Diseases 0.000 claims description 3
• 230000003213 activating effect Effects 0.000 claims description 3
• 230000001919 adrenal effect Effects 0.000 claims description 3
• 208000005881 bovine spongiform encephalopathy Diseases 0.000 claims description 3
• 230000002490 cerebral effect Effects 0.000 claims description 3
• 206010008129 cerebral palsy Diseases 0.000 claims description 3
• 230000009089 cytolysis Effects 0.000 claims description 3
• 230000003111 delayed effect Effects 0.000 claims description 3
• 208000033679 diabetic kidney disease Diseases 0.000 claims description 3
• 125000004494 ethyl ester group Chemical group 0.000 claims description 3
• 230000003176 fibrotic effect Effects 0.000 claims description 3
• 230000002008 hemorrhagic effect Effects 0.000 claims description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
• 208000014674 injury Diseases 0.000 claims description 3
• 206010025135 lupus erythematosus Diseases 0.000 claims description 3
• 230000002438 mitochondrial effect Effects 0.000 claims description 3
• 230000036457 multidrug resistance Effects 0.000 claims description 3
• 210000005036 nerve Anatomy 0.000 claims description 3
• 208000021090 palsy Diseases 0.000 claims description 3
• 210000000278 spinal cord Anatomy 0.000 claims description 3
• 230000002269 spontaneous effect Effects 0.000 claims description 3
• 238000002054 transplantation Methods 0.000 claims description 3
• 201000001862 viral hepatitis Diseases 0.000 claims description 3
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 2
• 208000030507 AIDS Diseases 0.000 claims description 2
• 208000007122 AIDS-Associated Nephropathy Diseases 0.000 claims description 2
• 206010000748 Acute febrile neutrophilic dermatosis Diseases 0.000 claims description 2
• 206010048799 Acute generalised exanthematous pustulosis Diseases 0.000 claims description 2
• 231100000104 Acute generalised exanthematous pustulosis Toxicity 0.000 claims description 2
• 208000005441 Acute generalized exanthematous pustulosis Diseases 0.000 claims description 2
• 208000032194 Acute haemorrhagic leukoencephalitis Diseases 0.000 claims description 2
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 2
• 208000024985 Alport syndrome Diseases 0.000 claims description 2
• 206010002383 Angina Pectoris Diseases 0.000 claims description 2
• 208000000103 Anorexia Nervosa Diseases 0.000 claims description 2
• 206010003210 Arteriosclerosis Diseases 0.000 claims description 2
• 208000033116 Asbestos intoxication Diseases 0.000 claims description 2
• 206010003591 Ataxia Diseases 0.000 claims description 2
• 206010003594 Ataxia telangiectasia Diseases 0.000 claims description 2
• 102000014461 Ataxins Human genes 0.000 claims description 2
• 108010078286 Ataxins Proteins 0.000 claims description 2
• 201000001320 Atherosclerosis Diseases 0.000 claims description 2
• 206010003827 Autoimmune hepatitis Diseases 0.000 claims description 2
• 208000027496 Behcet disease Diseases 0.000 claims description 2
• 208000009137 Behcet syndrome Diseases 0.000 claims description 2
• DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 claims description 2
• 208000014644 Brain disease Diseases 0.000 claims description 2
• 206010068597 Bulbospinal muscular atrophy congenital Diseases 0.000 claims description 2
• 208000033647 Classic progressive supranuclear palsy syndrome Diseases 0.000 claims description 2
• 208000010200 Cockayne syndrome Diseases 0.000 claims description 2
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 2
• 208000020406 Creutzfeldt Jacob disease Diseases 0.000 claims description 2
• 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 claims description 2
• 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 2
• 208000011231 Crohn disease Diseases 0.000 claims description 2
• 241000701022 Cytomegalovirus Species 0.000 claims description 2
• 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 2
• 208000001708 Dupuytren contracture Diseases 0.000 claims description 2
• 206010049020 Encephalitis periaxialis diffusa Diseases 0.000 claims description 2
• 208000032274 Encephalopathy Diseases 0.000 claims description 2
• 206010015216 Erythema marginatum Diseases 0.000 claims description 2
• 206010016654 Fibrosis Diseases 0.000 claims description 2
• 206010018364 Glomerulonephritis Diseases 0.000 claims description 2
• 201000005569 Gout Diseases 0.000 claims description 2
• 206010018691 Granuloma Diseases 0.000 claims description 2
• 208000003807 Graves Disease Diseases 0.000 claims description 2
• 208000015023 Graves' disease Diseases 0.000 claims description 2
• 206010070737 HIV associated nephropathy Diseases 0.000 claims description 2
• 208000030836 Hashimoto thyroiditis Diseases 0.000 claims description 2
• 206010019196 Head injury Diseases 0.000 claims description 2
• 206010019280 Heart failures Diseases 0.000 claims description 2
• 206010019315 Heart transplant rejection Diseases 0.000 claims description 2
• 208000032087 Hereditary Leber Optic Atrophy Diseases 0.000 claims description 2
• 206010020772 Hypertension Diseases 0.000 claims description 2
• 208000010159 IgA glomerulonephritis Diseases 0.000 claims description 2
• 206010021263 IgA nephropathy Diseases 0.000 claims description 2
• 208000014919 IgG4-related retroperitoneal fibrosis Diseases 0.000 claims description 2
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
• 208000005615 Interstitial Cystitis Diseases 0.000 claims description 2
• 206010059176 Juvenile idiopathic arthritis Diseases 0.000 claims description 2
• 208000002260 Keloid Diseases 0.000 claims description 2
• 208000027747 Kennedy disease Diseases 0.000 claims description 2
• 206010023358 Keratoderma blenorrhagica Diseases 0.000 claims description 2
• 201000003533 Leber congenital amaurosis Diseases 0.000 claims description 2
• 208000006136 Leigh Disease Diseases 0.000 claims description 2
• 208000017507 Leigh syndrome Diseases 0.000 claims description 2
• 208000009829 Lewy Body Disease Diseases 0.000 claims description 2
• 201000002832 Lewy body dementia Diseases 0.000 claims description 2
• 206010024715 Liver transplant rejection Diseases 0.000 claims description 2
• 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
• 206010051604 Lung transplant rejection Diseases 0.000 claims description 2
• 208000005777 Lupus Nephritis Diseases 0.000 claims description 2
• 208000002720 Malnutrition Diseases 0.000 claims description 2
• 206010058799 Mitochondrial encephalomyopathy Diseases 0.000 claims description 2
• 208000034486 Multi-organ failure Diseases 0.000 claims description 2
• 208000010718 Multiple Organ Failure Diseases 0.000 claims description 2
• 208000001089 Multiple system atrophy Diseases 0.000 claims description 2
• 201000002481 Myositis Diseases 0.000 claims description 2
• 206010029240 Neuritis Diseases 0.000 claims description 2
• 201000009053 Neurodermatitis Diseases 0.000 claims description 2
• 208000007125 Neurotoxicity Syndromes Diseases 0.000 claims description 2
• 208000014060 Niemann-Pick disease Diseases 0.000 claims description 2
• 208000002804 Osteochondritis Diseases 0.000 claims description 2
• 201000009859 Osteochondrosis Diseases 0.000 claims description 2
• 206010034665 Peritoneal fibrosis Diseases 0.000 claims description 2
• 206010035664 Pneumonia Diseases 0.000 claims description 2
• 206010036030 Polyarthritis Diseases 0.000 claims description 2
• 206010036105 Polyneuropathy Diseases 0.000 claims description 2
• 206010036376 Postherpetic Neuralgia Diseases 0.000 claims description 2
• 208000032319 Primary lateral sclerosis Diseases 0.000 claims description 2
• 208000024777 Prion disease Diseases 0.000 claims description 2
• 201000004681 Psoriasis Diseases 0.000 claims description 2
• 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 2
• 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 2
• 206010037391 Pulmonary granuloma Diseases 0.000 claims description 2
• 206010037575 Pustular psoriasis Diseases 0.000 claims description 2
• 208000032056 Radiation Fibrosis Syndrome Diseases 0.000 claims description 2
• 101100240886 Rattus norvegicus Nptx2 gene Proteins 0.000 claims description 2
• 208000005587 Refsum Disease Diseases 0.000 claims description 2
• 208000033464 Reiter syndrome Diseases 0.000 claims description 2
• 206010063837 Reperfusion injury Diseases 0.000 claims description 2
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 2
• 206010038979 Retroperitoneal fibrosis Diseases 0.000 claims description 2
• 206010039085 Rhinitis allergic Diseases 0.000 claims description 2
• 208000021811 Sandhoff disease Diseases 0.000 claims description 2
• 208000021235 Schilder disease Diseases 0.000 claims description 2
• 206010040642 Sickle cell anaemia with crisis Diseases 0.000 claims description 2
• 201000010001 Silicosis Diseases 0.000 claims description 2
• 208000021386 Sjogren Syndrome Diseases 0.000 claims description 2
• 208000009415 Spinocerebellar Ataxias Diseases 0.000 claims description 2
• 208000005716 Subacute Combined Degeneration Diseases 0.000 claims description 2
• 206010042342 Subcorneal pustular dermatosis Diseases 0.000 claims description 2
• 208000010265 Sweet syndrome Diseases 0.000 claims description 2
• 201000009594 Systemic Scleroderma Diseases 0.000 claims description 2
• 206010042953 Systemic sclerosis Diseases 0.000 claims description 2
• 208000031737 Tissue Adhesions Diseases 0.000 claims description 2
• 231100000076 Toxic encephalopathy Toxicity 0.000 claims description 2
• 206010044221 Toxic encephalopathy Diseases 0.000 claims description 2
• 206010044248 Toxic shock syndrome Diseases 0.000 claims description 2
• 231100000650 Toxic shock syndrome Toxicity 0.000 claims description 2
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 2
• 206010046298 Upper motor neurone lesion Diseases 0.000 claims description 2
• 208000024780 Urticaria Diseases 0.000 claims description 2
• 206010046851 Uveitis Diseases 0.000 claims description 2
• 208000014926 Vesiculobullous Skin disease Diseases 0.000 claims description 2
• 208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 claims description 2
• 206010051895 acute chest syndrome Diseases 0.000 claims description 2
• 208000002552 acute disseminated encephalomyelitis Diseases 0.000 claims description 2
• 208000012998 acute renal failure Diseases 0.000 claims description 2
• 208000030597 adult Refsum disease Diseases 0.000 claims description 2
• 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 2
• 201000009961 allergic asthma Diseases 0.000 claims description 2
• 201000010105 allergic rhinitis Diseases 0.000 claims description 2
• 230000007815 allergy Effects 0.000 claims description 2
• 238000002399 angioplasty Methods 0.000 claims description 2
• 239000002246 antineoplastic agent Substances 0.000 claims description 2
• 208000011775 arteriosclerosis disease Diseases 0.000 claims description 2
• 206010003230 arteritis Diseases 0.000 claims description 2
• 206010003441 asbestosis Diseases 0.000 claims description 2
• 201000004562 autosomal dominant cerebellar ataxia Diseases 0.000 claims description 2
• 210000004227 basal ganglia Anatomy 0.000 claims description 2
• IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 claims description 2
• 208000013687 bullous systemic lupus erythematosus Diseases 0.000 claims description 2
• 230000000747 cardiac effect Effects 0.000 claims description 2
• 230000004663 cell proliferation Effects 0.000 claims description 2
• 208000015114 central nervous system disease Diseases 0.000 claims description 2
• 208000023819 chronic asthma Diseases 0.000 claims description 2
• 208000020832 chronic kidney disease Diseases 0.000 claims description 2
• 230000002566 clonic effect Effects 0.000 claims description 2
• 230000001054 cortical effect Effects 0.000 claims description 2
• 238000002316 cosmetic surgery Methods 0.000 claims description 2
• 229940127089 cytotoxic agent Drugs 0.000 claims description 2
• 238000000502 dialysis Methods 0.000 claims description 2
• 208000010643 digestive system disease Diseases 0.000 claims description 2
• 206010014599 encephalitis Diseases 0.000 claims description 2
• 206010015037 epilepsy Diseases 0.000 claims description 2
• 208000012814 erosive pustular dermatosis of the scalp Diseases 0.000 claims description 2
• 230000004761 fibrosis Effects 0.000 claims description 2
• ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims description 2
• 208000018685 gastrointestinal system disease Diseases 0.000 claims description 2
• 206010061989 glomerulosclerosis Diseases 0.000 claims description 2
• 208000003215 hereditary nephritis Diseases 0.000 claims description 2
• 208000002557 hidradenitis Diseases 0.000 claims description 2
• 230000000968 intestinal effect Effects 0.000 claims description 2
• 208000012947 ischemia reperfusion injury Diseases 0.000 claims description 2
• 201000002215 juvenile rheumatoid arthritis Diseases 0.000 claims description 2
• 210000001117 keloid Anatomy 0.000 claims description 2
• 208000006443 lactic acidosis Diseases 0.000 claims description 2
• 229940063711 lasix Drugs 0.000 claims description 2
• 201000010901 lateral sclerosis Diseases 0.000 claims description 2
• 208000036546 leukodystrophy Diseases 0.000 claims description 2
• 201000005202 lung cancer Diseases 0.000 claims description 2
• 208000020816 lung neoplasm Diseases 0.000 claims description 2
• 230000003211 malignant effect Effects 0.000 claims description 2
• 230000001071 malnutrition Effects 0.000 claims description 2
• 235000000824 malnutrition Nutrition 0.000 claims description 2
• 239000004579 marble Substances 0.000 claims description 2
• 201000005518 mononeuropathy Diseases 0.000 claims description 2
• 208000005264 motor neuron disease Diseases 0.000 claims description 2
• 208000029744 multiple organ dysfunction syndrome Diseases 0.000 claims description 2
• 206010028537 myelofibrosis Diseases 0.000 claims description 2
• 208000010125 myocardial infarction Diseases 0.000 claims description 2
• 201000003631 narcolepsy Diseases 0.000 claims description 2
• 208000008795 neuromyelitis optica Diseases 0.000 claims description 2
• 201000001119 neuropathy Diseases 0.000 claims description 2
• 230000007823 neuropathy Effects 0.000 claims description 2
• 208000002040 neurosyphilis Diseases 0.000 claims description 2
• 208000015380 nutritional deficiency disease Diseases 0.000 claims description 2
• 208000033808 peripheral neuropathy Diseases 0.000 claims description 2
• 208000030428 polyarticular arthritis Diseases 0.000 claims description 2
• 208000019629 polyneuritis Diseases 0.000 claims description 2
• 230000002265 prevention Effects 0.000 claims description 2
• 208000032207 progressive 1 supranuclear palsy Diseases 0.000 claims description 2
• 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 2
• 208000005069 pulmonary fibrosis Diseases 0.000 claims description 2
• 208000002815 pulmonary hypertension Diseases 0.000 claims description 2
• 201000010914 pustulosis of palm and sole Diseases 0.000 claims description 2
• 208000011797 pustulosis palmaris et plantaris Diseases 0.000 claims description 2
• 230000000637 radiosensitizating effect Effects 0.000 claims description 2
• 208000002574 reactive arthritis Diseases 0.000 claims description 2
• 238000007634 remodeling Methods 0.000 claims description 2
• 208000010157 sclerosing cholangitis Diseases 0.000 claims description 2
• 208000007056 sickle cell anemia Diseases 0.000 claims description 2
• 208000017520 skin disease Diseases 0.000 claims description 2
• 208000002320 spinal muscular atrophy Diseases 0.000 claims description 2
• 231100000240 steatosis hepatitis Toxicity 0.000 claims description 2
• 230000009885 systemic effect Effects 0.000 claims description 2
• 208000002025 tabes dorsalis Diseases 0.000 claims description 2
• 210000002435 tendon Anatomy 0.000 claims description 2
• 229940104230 thymidine Drugs 0.000 claims description 2
• 230000001052 transient effect Effects 0.000 claims description 2
• 230000008733 trauma Effects 0.000 claims description 2
• 208000025086 undetermined colitis Diseases 0.000 claims description 2
• 206010037888 Rash pustular Diseases 0.000 claims 2
• 208000029561 pustule Diseases 0.000 claims 2
• VXNZUUAINFGPBY-NMQOAUCRSA-N 2,3-dideuteriobut-1-ene Chemical compound [2H]C(=C)C(C)[2H] VXNZUUAINFGPBY-NMQOAUCRSA-N 0.000 claims 1
• 208000003343 Antiphospholipid Syndrome Diseases 0.000 claims 1
• 102000007371 Ataxin-3 Human genes 0.000 claims 1
• 241000589969 Borreliella burgdorferi Species 0.000 claims 1
• 206010015108 Epstein-Barr virus infection Diseases 0.000 claims 1
• 201000011240 Frontotemporal dementia Diseases 0.000 claims 1
• 206010048804 Kearns-Sayre syndrome Diseases 0.000 claims 1
• 208000035172 MERRF Diseases 0.000 claims 1
• 208000002569 Machado-Joseph Disease Diseases 0.000 claims 1
• 206010028372 Muscular weakness Diseases 0.000 claims 1
• 208000003926 Myelitis Diseases 0.000 claims 1
• 206010028851 Necrosis Diseases 0.000 claims 1
• 208000000609 Pick Disease of the Brain Diseases 0.000 claims 1
• 208000036834 Spinocerebellar ataxia type 3 Diseases 0.000 claims 1
• 230000003628 erosive effect Effects 0.000 claims 1
• 210000001652 frontal lobe Anatomy 0.000 claims 1
• 210000001503 joint Anatomy 0.000 claims 1
• 208000018937 joint inflammation Diseases 0.000 claims 1
• 208000017169 kidney disease Diseases 0.000 claims 1
• 230000036473 myasthenia Effects 0.000 claims 1
• 230000017074 necrotic cell death Effects 0.000 claims 1
• 210000000440 neutrophil Anatomy 0.000 claims 1
• 208000025487 periodic fever syndrome Diseases 0.000 claims 1
• 201000003086 pulmonary systemic sclerosis Diseases 0.000 claims 1
• 208000009954 pyoderma gangrenosum Diseases 0.000 claims 1
• 230000010410 reperfusion Effects 0.000 claims 1
• 230000002441 reversible effect Effects 0.000 claims 1
• 210000004761 scalp Anatomy 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 19
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 41
• 239000000203 mixture Substances 0.000 description 25
• NKHAVTQWNUWKEO-UHFFFAOYSA-N fumaric acid monomethyl ester Natural products COC(=O)C=CC(O)=O NKHAVTQWNUWKEO-UHFFFAOYSA-N 0.000 description 22
• NKHAVTQWNUWKEO-NSCUHMNNSA-N monomethyl fumarate Chemical compound COC(=O)\C=C\C(O)=O NKHAVTQWNUWKEO-NSCUHMNNSA-N 0.000 description 22
• 235000019439 ethyl acetate Nutrition 0.000 description 21
• 229940005650 monomethyl fumarate Drugs 0.000 description 21
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
• 102000004190 Enzymes Human genes 0.000 description 15
• 108090000790 Enzymes Proteins 0.000 description 15
• 230000000694 effects Effects 0.000 description 15
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 14
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 14
• 230000004913 activation Effects 0.000 description 14
• 238000010171 animal model Methods 0.000 description 14
• 210000004556 brain Anatomy 0.000 description 14
• 229940124597 therapeutic agent Drugs 0.000 description 14
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 14
• 239000000243 solution Substances 0.000 description 13
• NKHAVTQWNUWKEO-SMQGVBCRSA-N (e)-4-oxo-4-(trideuteriomethoxy)but-2-enoic acid Chemical compound [2H]C([2H])([2H])OC(=O)\C=C\C(O)=O NKHAVTQWNUWKEO-SMQGVBCRSA-N 0.000 description 12
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• 239000007787 solid Substances 0.000 description 12
• 108090000623 proteins and genes Proteins 0.000 description 11
• PHCSTEJVICOGEJ-UHFFFAOYSA-N 2-hydroxy-1-morpholin-4-ylethanone Chemical compound OCC(=O)N1CCOCC1 PHCSTEJVICOGEJ-UHFFFAOYSA-N 0.000 description 10
• 108700032225 Antioxidant Response Elements Proteins 0.000 description 10
• 101150116862 KEAP1 gene Proteins 0.000 description 10
• 238000004458 analytical method Methods 0.000 description 10
• 239000003795 chemical substances by application Substances 0.000 description 10
• 239000008194 pharmaceutical composition Substances 0.000 description 10
• 239000011734 sodium Substances 0.000 description 10
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
• 239000003963 antioxidant agent Substances 0.000 description 9
• 238000009472 formulation Methods 0.000 description 9
• 238000004128 high performance liquid chromatography Methods 0.000 description 9
• 230000036542 oxidative stress Effects 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
• 208000012902 Nervous system disease Diseases 0.000 description 8
• 230000003078 antioxidant effect Effects 0.000 description 8
• 239000012043 crude product Substances 0.000 description 8
• 239000000546 pharmaceutical excipient Substances 0.000 description 8
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 8
• NKHAVTQWNUWKEO-XNHULNRKSA-N (E)-2,3-dideuterio-4-methoxy-4-oxobut-2-enoic acid Chemical compound OC(=O)C(/[2H])=C(\[2H])C(=O)OC NKHAVTQWNUWKEO-XNHULNRKSA-N 0.000 description 7
• 241000700159 Rattus Species 0.000 description 7
• 229940079593 drug Drugs 0.000 description 7
• 238000011156 evaluation Methods 0.000 description 7
• 239000000825 pharmaceutical preparation Substances 0.000 description 7
• 238000002953 preparative HPLC Methods 0.000 description 7
• 239000011541 reaction mixture Substances 0.000 description 7
• 208000024891 symptom Diseases 0.000 description 7
• 238000012360 testing method Methods 0.000 description 7
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 6
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
• 239000005089 Luciferase Substances 0.000 description 6
• 241001465754 Metazoa Species 0.000 description 6
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
• 208000036110 Neuroinflammatory disease Diseases 0.000 description 6
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
• 235000006708 antioxidants Nutrition 0.000 description 6
• 210000004369 blood Anatomy 0.000 description 6
• 239000008280 blood Substances 0.000 description 6
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 6
• 239000002552 dosage form Substances 0.000 description 6
• 239000000706 filtrate Substances 0.000 description 6
• 238000011010 flushing procedure Methods 0.000 description 6
• 125000001072 heteroaryl group Chemical group 0.000 description 6
• 238000003305 oral gavage Methods 0.000 description 6
• 239000012044 organic layer Substances 0.000 description 6
• 239000000047 product Substances 0.000 description 6
• 125000001424 substituent group Chemical group 0.000 description 6
• 230000001225 therapeutic effect Effects 0.000 description 6
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 5
• 108060001084 Luciferase Proteins 0.000 description 5
• 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 description 5
• 229960001138 acetylsalicylic acid Drugs 0.000 description 5
• 150000001298 alcohols Chemical class 0.000 description 5
• 230000008901 benefit Effects 0.000 description 5
• 210000003169 central nervous system Anatomy 0.000 description 5
• 239000013058 crude material Substances 0.000 description 5
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 5
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 5
• 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 5
• 230000035772 mutation Effects 0.000 description 5
• 230000003959 neuroinflammation Effects 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
• 238000012552 review Methods 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
• 239000002904 solvent Substances 0.000 description 5
• 210000001519 tissue Anatomy 0.000 description 5
• 108010018924 Heme Oxygenase-1 Proteins 0.000 description 4
• 101000973778 Homo sapiens NAD(P)H dehydrogenase [quinone] 1 Proteins 0.000 description 4
• 206010061218 Inflammation Diseases 0.000 description 4
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 4
• 102100022365 NAD(P)H dehydrogenase [quinone] 1 Human genes 0.000 description 4
• 208000025966 Neurological disease Diseases 0.000 description 4
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 4
• 108090000185 alpha-Synuclein Proteins 0.000 description 4
• 125000004429 atom Chemical group 0.000 description 4
• 125000002837 carbocyclic group Chemical group 0.000 description 4
• 235000010980 cellulose Nutrition 0.000 description 4
• 229920002678 cellulose Polymers 0.000 description 4
• 239000001913 cellulose Substances 0.000 description 4
• 230000008859 change Effects 0.000 description 4
• 238000006243 chemical reaction Methods 0.000 description 4
• 235000005687 corn oil Nutrition 0.000 description 4
• 239000002285 corn oil Substances 0.000 description 4
• 230000007547 defect Effects 0.000 description 4
• 238000001514 detection method Methods 0.000 description 4
• 238000001784 detoxification Methods 0.000 description 4
• 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 4
• 230000004054 inflammatory process Effects 0.000 description 4
• 230000003902 lesion Effects 0.000 description 4
• 238000004519 manufacturing process Methods 0.000 description 4
• 210000001577 neostriatum Anatomy 0.000 description 4
• 230000000324 neuroprotective effect Effects 0.000 description 4
• 238000012746 preparative thin layer chromatography Methods 0.000 description 4
• 102000004169 proteins and genes Human genes 0.000 description 4
• 102000005962 receptors Human genes 0.000 description 4
• 108020003175 receptors Proteins 0.000 description 4
• 230000000306 recurrent effect Effects 0.000 description 4
• 230000001105 regulatory effect Effects 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 241000701161 unidentified adenovirus Species 0.000 description 4
• 102100028908 Cullin-3 Human genes 0.000 description 3
• 101710094482 Cullin-3 Proteins 0.000 description 3
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
• 102100030643 Hydroxycarboxylic acid receptor 2 Human genes 0.000 description 3
• 108010005716 Interferon beta-1a Proteins 0.000 description 3
• 241000699670 Mus sp. Species 0.000 description 3
• 108020000284 NAD(P)H dehydrogenase (quinone) Proteins 0.000 description 3
• 102000004316 Oxidoreductases Human genes 0.000 description 3
• 108090000854 Oxidoreductases Proteins 0.000 description 3
• 239000002202 Polyethylene glycol Substances 0.000 description 3
• 206010057190 Respiratory tract infections Diseases 0.000 description 3
• FTALBRSUTCGOEG-UHFFFAOYSA-N Riluzole Chemical compound C1=C(OC(F)(F)F)C=C2SC(N)=NC2=C1 FTALBRSUTCGOEG-UHFFFAOYSA-N 0.000 description 3
• 125000000217 alkyl group Chemical group 0.000 description 3
• 102000003802 alpha-Synuclein Human genes 0.000 description 3
• 229960003805 amantadine Drugs 0.000 description 3
• DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 3
• 239000007864 aqueous solution Substances 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
• 230000003376 axonal effect Effects 0.000 description 3
• 125000004432 carbon atom Chemical group C* 0.000 description 3
• 239000001768 carboxy methyl cellulose Substances 0.000 description 3
• 230000003197 catalytic effect Effects 0.000 description 3
• 239000003153 chemical reaction reagent Substances 0.000 description 3
• 238000002648 combination therapy Methods 0.000 description 3
• 239000006184 cosolvent Substances 0.000 description 3
• 125000000753 cycloalkyl group Chemical group 0.000 description 3
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 3
• 208000035475 disorder Diseases 0.000 description 3
• 229960003638 dopamine Drugs 0.000 description 3
• 239000003937 drug carrier Substances 0.000 description 3
• 230000003492 excitotoxic effect Effects 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
• 239000012634 fragment Substances 0.000 description 3
• 230000014509 gene expression Effects 0.000 description 3
• 239000010410 layer Substances 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 229920000609 methyl cellulose Polymers 0.000 description 3
• 150000004702 methyl esters Chemical class 0.000 description 3
• 238000010172 mouse model Methods 0.000 description 3
• 230000001537 neural effect Effects 0.000 description 3
• 210000002569 neuron Anatomy 0.000 description 3
• 230000005937 nuclear translocation Effects 0.000 description 3
• FIKAKWIAUPDISJ-UHFFFAOYSA-L paraquat dichloride Chemical compound [Cl-].[Cl-].C1=C[N+](C)=CC=C1C1=CC=[N+](C)C=C1 FIKAKWIAUPDISJ-UHFFFAOYSA-L 0.000 description 3
• 206010063401 primary progressive multiple sclerosis Diseases 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• 125000006413 ring segment Chemical group 0.000 description 3
• 241000894007 species Species 0.000 description 3
• 238000013518 transcription Methods 0.000 description 3
• 230000035897 transcription Effects 0.000 description 3
• 239000003981 vehicle Substances 0.000 description 3
• 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 2
• LSWRBVSEWBWTDR-UHFFFAOYSA-N 2-hydroxyethyl benzoate Chemical compound OCCOC(=O)C1=CC=CC=C1 LSWRBVSEWBWTDR-UHFFFAOYSA-N 0.000 description 2
• XLYMOEINVGRTEX-UHFFFAOYSA-N 4-ethoxy-4-oxobut-2-enoic acid Chemical compound CCOC(=O)C=CC(O)=O XLYMOEINVGRTEX-UHFFFAOYSA-N 0.000 description 2
• 208000031277 Amaurotic familial idiocy Diseases 0.000 description 2
• 208000023275 Autoimmune disease Diseases 0.000 description 2
• 206010006187 Breast cancer Diseases 0.000 description 2
• 208000026310 Breast neoplasm Diseases 0.000 description 2
• 241000244203 Caenorhabditis elegans Species 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
• 229920000858 Cyclodextrin Polymers 0.000 description 2
• 241000252212 Danio rerio Species 0.000 description 2
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
• 102000008857 Ferritin Human genes 0.000 description 2
• 108050000784 Ferritin Proteins 0.000 description 2
• 238000008416 Ferritin Methods 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• 102000016354 Glucuronosyltransferase Human genes 0.000 description 2
• 108010092364 Glucuronosyltransferase Proteins 0.000 description 2
• 108010070675 Glutathione transferase Proteins 0.000 description 2
• 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 2
• 101150062179 II gene Proteins 0.000 description 2
• 206010021531 Impetigo Diseases 0.000 description 2
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
• 241000711466 Murine hepatitis virus Species 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 2
• 102000004960 NAD(P)H dehydrogenase (quinone) Human genes 0.000 description 2
• 108010017405 NRH - quinone oxidoreductase2 Proteins 0.000 description 2
• 208000002537 Neuronal Ceroid-Lipofuscinoses Diseases 0.000 description 2
• 206010037660 Pyrexia Diseases 0.000 description 2
• 101001109714 Rhizobium meliloti (strain 1021) NAD(P)H dehydrogenase (quinone) 1 Proteins 0.000 description 2
• 102100022353 Ribosyldihydronicotinamide dehydrogenase [quinone] Human genes 0.000 description 2
• 241000283984 Rodentia Species 0.000 description 2
• YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• 102000002933 Thioredoxin Human genes 0.000 description 2
• XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 2
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
• 239000013543 active substance Substances 0.000 description 2
• 230000002411 adverse Effects 0.000 description 2
• 230000032683 aging Effects 0.000 description 2
• 239000000556 agonist Substances 0.000 description 2
• 125000003342 alkenyl group Chemical group 0.000 description 2
• 229920013820 alkyl cellulose Polymers 0.000 description 2
• 125000003118 aryl group Chemical group 0.000 description 2
• 210000003050 axon Anatomy 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• 230000015572 biosynthetic process Effects 0.000 description 2
• 210000005013 brain tissue Anatomy 0.000 description 2
• 239000012267 brine Substances 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 235000011089 carbon dioxide Nutrition 0.000 description 2
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 230000015556 catabolic process Effects 0.000 description 2
• 239000011248 coating agent Substances 0.000 description 2
• 238000000576 coating method Methods 0.000 description 2
• 230000001276 controlling effect Effects 0.000 description 2
• 125000000392 cycloalkenyl group Chemical group 0.000 description 2
• 210000000805 cytoplasm Anatomy 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• 238000006731 degradation reaction Methods 0.000 description 2
• 238000010790 dilution Methods 0.000 description 2
• 239000012895 dilution Substances 0.000 description 2
• 229960003530 donepezil Drugs 0.000 description 2
• 239000003596 drug target Substances 0.000 description 2
• 231100000063 excitotoxicity Toxicity 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 238000007429 general method Methods 0.000 description 2
• 230000002068 genetic effect Effects 0.000 description 2
• 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 2
• 239000008187 granular material Substances 0.000 description 2
• 230000036541 health Effects 0.000 description 2
• 239000000833 heterodimer Substances 0.000 description 2
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
• UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
• 230000001976 improved effect Effects 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 230000006698 induction Effects 0.000 description 2
• 210000001630 jejunum Anatomy 0.000 description 2
• 208000017476 juvenile neuronal ceroid lipofuscinosis Diseases 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 210000004558 lewy body Anatomy 0.000 description 2
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 230000001404 mediated effect Effects 0.000 description 2
• 239000002207 metabolite Substances 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• 235000010981 methylcellulose Nutrition 0.000 description 2
• 239000001923 methylcellulose Substances 0.000 description 2
• 206010028417 myasthenia gravis Diseases 0.000 description 2
• 230000000626 neurodegenerative effect Effects 0.000 description 2
• 210000002682 neurofibrillary tangle Anatomy 0.000 description 2
• 210000004498 neuroglial cell Anatomy 0.000 description 2
• 201000007607 neuronal ceroid lipofuscinosis 3 Diseases 0.000 description 2
• 230000009994 neurotransmitter pathway Effects 0.000 description 2
• 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 2
• DIVDFFZHCJEHGG-UHFFFAOYSA-N oxidopamine Chemical compound NCCC1=CC(O)=C(O)C=C1O DIVDFFZHCJEHGG-UHFFFAOYSA-N 0.000 description 2
• 230000008506 pathogenesis Effects 0.000 description 2
• 229940124531 pharmaceutical excipient Drugs 0.000 description 2
• 230000003285 pharmacodynamic effect Effects 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 235000018102 proteins Nutrition 0.000 description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
• 150000003254 radicals Chemical class 0.000 description 2
• 229960004181 riluzole Drugs 0.000 description 2
• 201000008628 secondary progressive multiple sclerosis Diseases 0.000 description 2
• 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 2
• 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 2
• 230000019491 signal transduction Effects 0.000 description 2
• PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
• 210000000952 spleen Anatomy 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 230000000638 stimulation Effects 0.000 description 2
• 238000003756 stirring Methods 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• 229940121136 tecfidera 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
• 108060008226 thioredoxin Proteins 0.000 description 2
• 238000013254 toxin-induced animal model Methods 0.000 description 2
• 238000011830 transgenic mouse model Methods 0.000 description 2
• AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 1
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
• SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
• KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
• WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 description 1
• RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
• ZEUITGRIYCTCEM-KRWDZBQOSA-N (S)-duloxetine Chemical compound C1([C@@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-KRWDZBQOSA-N 0.000 description 1
• XLYMOEINVGRTEX-ONEGZZNKSA-N (e)-4-ethoxy-4-oxobut-2-enoic acid Chemical compound CCOC(=O)\C=C\C(O)=O XLYMOEINVGRTEX-ONEGZZNKSA-N 0.000 description 1
• DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 description 1
• WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• AUFIRGPROMANKW-UHFFFAOYSA-N 1-methyl-3,6-dihydro-2h-pyridine Chemical compound CN1CCC=CC1 AUFIRGPROMANKW-UHFFFAOYSA-N 0.000 description 1
• 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 1
• SPCKHVPPRJWQRZ-UHFFFAOYSA-N 2-benzhydryloxy-n,n-dimethylethanamine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 SPCKHVPPRJWQRZ-UHFFFAOYSA-N 0.000 description 1
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
• JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
• WBLZUCOIBUDNBV-UHFFFAOYSA-N 3-nitropropanoic acid Chemical compound OC(=O)CC[N+]([O-])=O WBLZUCOIBUDNBV-UHFFFAOYSA-N 0.000 description 1
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
• WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 description 1
• CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 description 1
• URFFPMJFOHTCLI-UHFFFAOYSA-N 4-morpholin-4-ylbutan-1-ol Chemical compound OCCCCN1CCOCC1 URFFPMJFOHTCLI-UHFFFAOYSA-N 0.000 description 1
• SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
• 102100031126 6-phosphogluconolactonase Human genes 0.000 description 1
• 108010029731 6-phosphogluconolactonase Proteins 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
• 101000889837 Aeropyrum pernix (strain ATCC 700893 / DSM 11879 / JCM 9820 / NBRC 100138 / K1) Protein CysO Proteins 0.000 description 1
• 208000011403 Alexander disease Diseases 0.000 description 1
• 102100028116 Amine oxidase [flavin-containing] B Human genes 0.000 description 1
• 208000000044 Amnesia Diseases 0.000 description 1
• 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
• 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
• 229920000856 Amylose Polymers 0.000 description 1
• 208000019901 Anxiety disease Diseases 0.000 description 1
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical group [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
• 206010006100 Bradykinesia Diseases 0.000 description 1
• 238000003737 Bright-Glo Luciferase Assay System Methods 0.000 description 1
• 208000011691 Burkitt lymphomas Diseases 0.000 description 1
• IVQCNNVSEICUEP-UHFFFAOYSA-N CC(CCCCCCCCCC=[N+]=[N-])(C)C Chemical compound CC(CCCCCCCCCC=[N+]=[N-])(C)C IVQCNNVSEICUEP-UHFFFAOYSA-N 0.000 description 1
• 101100393844 Caenorhabditis elegans gst-3 gene Proteins 0.000 description 1
• 208000022526 Canavan disease Diseases 0.000 description 1
• 101710167800 Capsid assembly scaffolding protein Proteins 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• 102000014914 Carrier Proteins Human genes 0.000 description 1
• 102100035882 Catalase Human genes 0.000 description 1
• 108010053835 Catalase Proteins 0.000 description 1
• 208000010693 Charcot-Marie-Tooth Disease Diseases 0.000 description 1
• 208000008964 Chemical and Drug Induced Liver Injury Diseases 0.000 description 1
• 229920001287 Chondroitin sulfate Polymers 0.000 description 1
• 206010008748 Chorea Diseases 0.000 description 1
• GDLIGKIOYRNHDA-UHFFFAOYSA-N Clomipramine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCN(C)C)C2=CC=CC=C21 GDLIGKIOYRNHDA-UHFFFAOYSA-N 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• 241001573498 Compacta Species 0.000 description 1
• 229920002785 Croscarmellose sodium Polymers 0.000 description 1
• DSRJIHMZAQEUJV-UHFFFAOYSA-N Cuprizon Chemical compound C1CCCCC1=NNC(=O)C(=O)NN=C1CCCCC1 DSRJIHMZAQEUJV-UHFFFAOYSA-N 0.000 description 1
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
• 206010011830 Cytomegalovirus hepatitis Diseases 0.000 description 1
• 108020004414 DNA Proteins 0.000 description 1
• 101710088194 Dehydrogenase Proteins 0.000 description 1
• 229940124186 Dehydrogenase inhibitor Drugs 0.000 description 1
• HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
• 239000004375 Dextrin Substances 0.000 description 1
• 229920001353 Dextrin Polymers 0.000 description 1
• 206010012735 Diarrhoea Diseases 0.000 description 1
• 241000255601 Drosophila melanogaster Species 0.000 description 1
• 102100023877 E3 ubiquitin-protein ligase RBX1 Human genes 0.000 description 1
• 101710095156 E3 ubiquitin-protein ligase RBX1 Proteins 0.000 description 1
• 102000005486 Epoxide hydrolase Human genes 0.000 description 1
• 108020002908 Epoxide hydrolase Proteins 0.000 description 1
• 108090000371 Esterases Proteins 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• 206010070246 Executive dysfunction Diseases 0.000 description 1
• 206010015719 Exsanguination Diseases 0.000 description 1
• 101710131282 FAD-linked oxidoreductase easE Proteins 0.000 description 1
• 108090000331 Firefly luciferases Proteins 0.000 description 1
• 206010064571 Gene mutation Diseases 0.000 description 1
• 208000010055 Globoid Cell Leukodystrophy Diseases 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
• 108010018962 Glucosephosphate Dehydrogenase Proteins 0.000 description 1
• 108010024636 Glutathione Proteins 0.000 description 1
• 108010063907 Glutathione Reductase Proteins 0.000 description 1
• 102000006587 Glutathione peroxidase Human genes 0.000 description 1
• 108700016172 Glutathione peroxidases Proteins 0.000 description 1
• 102100036442 Glutathione reductase, mitochondrial Human genes 0.000 description 1
• 208000004547 Hallucinations Diseases 0.000 description 1
• 102000002737 Heme Oxygenase-1 Human genes 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
• 208000000857 Hepatic Insufficiency Diseases 0.000 description 1
• 206010019663 Hepatic failure Diseases 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101000619542 Homo sapiens E3 ubiquitin-protein ligase parkin Proteins 0.000 description 1
• 101000843809 Homo sapiens Hydroxycarboxylic acid receptor 2 Proteins 0.000 description 1
• 101001013648 Homo sapiens Methionine synthase Proteins 0.000 description 1
• 101000605835 Homo sapiens Serine/threonine-protein kinase PINK1, mitochondrial Proteins 0.000 description 1
• 101000704557 Homo sapiens Sulfiredoxin-1 Proteins 0.000 description 1
• 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
• 108050004784 Huntingtin Proteins 0.000 description 1
• 101710125793 Hydroxycarboxylic acid receptor 2 Proteins 0.000 description 1
• 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
• 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
• 206010020649 Hyperkeratosis Diseases 0.000 description 1
• 208000006083 Hypokinesia Diseases 0.000 description 1
• HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
• 208000026350 Inborn Genetic disease Diseases 0.000 description 1
• 206010023126 Jaundice Diseases 0.000 description 1
• 208000007766 Kaposi sarcoma Diseases 0.000 description 1
• 102000004034 Kelch-Like ECH-Associated Protein 1 Human genes 0.000 description 1
• 108090000484 Kelch-Like ECH-Associated Protein 1 Proteins 0.000 description 1
• 208000028226 Krabbe disease Diseases 0.000 description 1
• 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 1
• WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
• 108010020246 Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 Proteins 0.000 description 1
• 102100032693 Leucine-rich repeat serine/threonine-protein kinase 2 Human genes 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 208000026139 Memory disease Diseases 0.000 description 1
• 102000003792 Metallothionein Human genes 0.000 description 1
• 108090000157 Metallothionein Proteins 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 108010062431 Monoamine oxidase Proteins 0.000 description 1
• 208000034578 Multiple myelomas Diseases 0.000 description 1
• 241001529936 Murinae Species 0.000 description 1
• 101100298488 Mus musculus Prdx1 gene Proteins 0.000 description 1
• 101100449771 Musca domestica Gst3 gene Proteins 0.000 description 1
• 206010052904 Musculoskeletal stiffness Diseases 0.000 description 1
• 102000006386 Myelin Proteins Human genes 0.000 description 1
• 108010083674 Myelin Proteins Proteins 0.000 description 1
• 208000033776 Myeloid Acute Leukemia Diseases 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
• 206010063663 Neuropsychiatric lupus Diseases 0.000 description 1
• 101710138657 Neurotoxin Proteins 0.000 description 1
• PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 1
• 241001420836 Ophthalmitis Species 0.000 description 1
• 101710199728 Oxidoreductase 1 Proteins 0.000 description 1
• AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 1
• 206010034912 Phobia Diseases 0.000 description 1
• 206010035226 Plasma cell myeloma Diseases 0.000 description 1
• RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
• 239000004372 Polyvinyl alcohol Substances 0.000 description 1
• 101710130420 Probable capsid assembly scaffolding protein Proteins 0.000 description 1
• 206010036790 Productive cough Diseases 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
• 101710104378 Putative malate oxidoreductase [NAD] Proteins 0.000 description 1
• 101710178916 RING-box protein 1 Proteins 0.000 description 1
• 238000011529 RT qPCR Methods 0.000 description 1
• 108700005075 Regulator Genes Proteins 0.000 description 1
• 206010038687 Respiratory distress Diseases 0.000 description 1
• 108091027981 Response element Proteins 0.000 description 1
• 241000219061 Rheum Species 0.000 description 1
• 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 1
• KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
• 101150055709 SNF1 gene Proteins 0.000 description 1
• 108700013394 SOD1 G93A Proteins 0.000 description 1
• 101710204410 Scaffold protein Proteins 0.000 description 1
• 241000710961 Semliki Forest virus Species 0.000 description 1
• 102100038376 Serine/threonine-protein kinase PINK1, mitochondrial Human genes 0.000 description 1
• 102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 description 1
• 241000710960 Sindbis virus Species 0.000 description 1
• 102000019259 Succinate Dehydrogenase Human genes 0.000 description 1
• 108010012901 Succinate Dehydrogenase Proteins 0.000 description 1
• 102100031797 Sulfiredoxin-1 Human genes 0.000 description 1
• 102000019197 Superoxide Dismutase Human genes 0.000 description 1
• 108010012715 Superoxide dismutase Proteins 0.000 description 1
• 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 1
• 102000013090 Thioredoxin-Disulfide Reductase Human genes 0.000 description 1
• 108010079911 Thioredoxin-disulfide reductase Proteins 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 102100028601 Transaldolase Human genes 0.000 description 1
• 108020004530 Transaldolase Proteins 0.000 description 1
• 108091023040 Transcription factor Proteins 0.000 description 1
• 102000040945 Transcription factor Human genes 0.000 description 1
• 102100033055 Transketolase Human genes 0.000 description 1
• 108010043652 Transketolase Proteins 0.000 description 1
• 206010052779 Transplant rejections Diseases 0.000 description 1
• 206010044565 Tremor Diseases 0.000 description 1
• 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
• HWHLPVGTWGOCJO-UHFFFAOYSA-N Trihexyphenidyl Chemical group C1CCCCC1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 HWHLPVGTWGOCJO-UHFFFAOYSA-N 0.000 description 1
• 108090000848 Ubiquitin Proteins 0.000 description 1
• 102000044159 Ubiquitin Human genes 0.000 description 1
• 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 1
• 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 1
• 102000057144 Uridine Diphosphate Glucose Dehydrogenase Human genes 0.000 description 1
• 108010054269 Uridine Diphosphate Glucose Dehydrogenase Proteins 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• 229930003427 Vitamin E Natural products 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• 238000009825 accumulation Methods 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 231100000354 acute hepatitis Toxicity 0.000 description 1
• 102000035181 adaptor proteins Human genes 0.000 description 1
• 108091005764 adaptor proteins Proteins 0.000 description 1
• 208000009956 adenocarcinoma Diseases 0.000 description 1
• 239000008476 aike Substances 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 125000000304 alkynyl group Chemical group 0.000 description 1
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
• 229960000836 amitriptyline Drugs 0.000 description 1
• KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 1
• 229960002519 amoxapine Drugs 0.000 description 1
• QWGDMFLQWFTERH-UHFFFAOYSA-N amoxapine Chemical compound C12=CC(Cl)=CC=C2OC2=CC=CC=C2N=C1N1CCNCC1 QWGDMFLQWFTERH-UHFFFAOYSA-N 0.000 description 1
• 239000012491 analyte Substances 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 230000001078 anti-cholinergic effect Effects 0.000 description 1
• 230000001028 anti-proliverative effect Effects 0.000 description 1
• 239000000427 antigen Substances 0.000 description 1
• 108091007433 antigens Proteins 0.000 description 1
• 102000036639 antigens Human genes 0.000 description 1
• 229940125715 antihistaminic agent Drugs 0.000 description 1
• 239000000739 antihistaminic agent Substances 0.000 description 1
• 239000003443 antiviral agent Substances 0.000 description 1
• 230000036506 anxiety Effects 0.000 description 1
• 229910052786 argon Inorganic materials 0.000 description 1
• 239000012131 assay buffer Substances 0.000 description 1
• 230000003140 astrocytic effect Effects 0.000 description 1
• 230000037147 athletic performance Effects 0.000 description 1
• 229940057415 aubagio Drugs 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• 230000005784 autoimmunity Effects 0.000 description 1
• 229940003504 avonex Drugs 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
• 230000006399 behavior Effects 0.000 description 1
• 230000003542 behavioural effect Effects 0.000 description 1
• GIJXKZJWITVLHI-PMOLBWCYSA-N benzatropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(C=1C=CC=CC=1)C1=CC=CC=C1 GIJXKZJWITVLHI-PMOLBWCYSA-N 0.000 description 1
• 229960001081 benzatropine Drugs 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 108091008324 binding proteins Proteins 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 150000001621 bismuth Chemical class 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 229960002802 bromocriptine Drugs 0.000 description 1
• OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 210000004899 c-terminal region Anatomy 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 229910052799 carbon Inorganic materials 0.000 description 1
• 239000012876 carrier material Substances 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
• 229960000590 celecoxib Drugs 0.000 description 1
• 238000000423 cell based assay Methods 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 230000002032 cellular defenses Effects 0.000 description 1
• 210000003710 cerebral cortex Anatomy 0.000 description 1
• CETPSERCERDGAM-UHFFFAOYSA-N ceric oxide Chemical compound O=[Ce]=O CETPSERCERDGAM-UHFFFAOYSA-N 0.000 description 1
• 229910000422 cerium(IV) oxide Inorganic materials 0.000 description 1
• SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 1
• 238000002038 chemiluminescence detection Methods 0.000 description 1
• 230000002113 chemopreventative effect Effects 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 230000001713 cholinergic effect Effects 0.000 description 1
• 229940059329 chondroitin sulfate Drugs 0.000 description 1
• 208000012601 choreatic disease Diseases 0.000 description 1
• 229960001653 citalopram Drugs 0.000 description 1
• 229960004606 clomipramine Drugs 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 230000007278 cognition impairment Effects 0.000 description 1
• 208000010877 cognitive disease Diseases 0.000 description 1
• 208000029742 colonic neoplasm Diseases 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 230000000295 complement effect Effects 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 229940125782 compound 2 Drugs 0.000 description 1
• 239000004020 conductor Substances 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 229960001681 croscarmellose sodium Drugs 0.000 description 1
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
• 229940097362 cyclodextrins Drugs 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
• 150000001944 cysteine derivatives Chemical class 0.000 description 1
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
• 238000007405 data analysis Methods 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000006735 deficit Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 229960003914 desipramine Drugs 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• FASDKYOPVNHBLU-SSDOTTSWSA-N dexpramipexole Chemical compound C1[C@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-SSDOTTSWSA-N 0.000 description 1
• 229950004920 dexpramipexole Drugs 0.000 description 1
• 235000019425 dextrin Nutrition 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• RAABOESOVLLHRU-UHFFFAOYSA-O diazenium Chemical compound [NH2+]=N RAABOESOVLLHRU-UHFFFAOYSA-O 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• 235000015872 dietary supplement Nutrition 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• 229960000520 diphenhydramine Drugs 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 150000004141 diterpene derivatives Chemical class 0.000 description 1
• 229940052760 dopamine agonists Drugs 0.000 description 1
• 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
• 210000005064 dopaminergic neuron Anatomy 0.000 description 1
• 229960005426 doxepin Drugs 0.000 description 1
• ODQWQRRAPPTVAG-GZTJUZNOSA-N doxepin Chemical compound C1OC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 ODQWQRRAPPTVAG-GZTJUZNOSA-N 0.000 description 1
• 229960002866 duloxetine Drugs 0.000 description 1
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 230000037149 energy metabolism Effects 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 210000003743 erythrocyte Anatomy 0.000 description 1
• 229960004341 escitalopram Drugs 0.000 description 1
• WSEQXVZVJXJVFP-FQEVSTJZSA-N escitalopram Chemical compound C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-FQEVSTJZSA-N 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• 235000019441 ethanol Nutrition 0.000 description 1
• SUPCQIBBMFXVTL-UHFFFAOYSA-N ethyl 2-methylprop-2-enoate Chemical compound CCOC(=O)C(C)=C SUPCQIBBMFXVTL-UHFFFAOYSA-N 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• 235000010944 ethyl methyl cellulose Nutrition 0.000 description 1
• 239000001761 ethyl methyl cellulose Substances 0.000 description 1
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
• 231100000318 excitotoxic Toxicity 0.000 description 1
• 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 210000001097 facial muscle Anatomy 0.000 description 1
• 201000006061 fatal familial insomnia Diseases 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 229960002464 fluoxetine Drugs 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 108020001507 fusion proteins Proteins 0.000 description 1
• 102000037865 fusion proteins Human genes 0.000 description 1
• 229960003980 galantamine Drugs 0.000 description 1
• ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 230000002496 gastric effect Effects 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 238000003208 gene overexpression Methods 0.000 description 1
• 208000016361 genetic disease Diseases 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• 229960003180 glutathione Drugs 0.000 description 1
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 101150113725 hd gene Proteins 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
• 125000004415 heterocyclylalkyl group Chemical group 0.000 description 1
• 238000000265 homogenisation Methods 0.000 description 1
• 229920002674 hyaluronan Polymers 0.000 description 1
• 229960003160 hyaluronic acid Drugs 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 150000002430 hydrocarbons Chemical group 0.000 description 1
• 229920013821 hydroxy alkyl cellulose Polymers 0.000 description 1
• 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
• 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
• 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
• 229960001680 ibuprofen Drugs 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 229960004801 imipramine Drugs 0.000 description 1
• BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 1
• 230000001900 immune effect Effects 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 210000003000 inclusion body Anatomy 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
• 208000015181 infectious disease Diseases 0.000 description 1
• 239000003112 inhibitor Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 229960004461 interferon beta-1a Drugs 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 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
• 238000011813 knockout mouse model Methods 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 229960004502 levodopa Drugs 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 239000012669 liquid formulation Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 229960001571 loperamide Drugs 0.000 description 1
• RDOIQAHITMMDAJ-UHFFFAOYSA-N loperamide Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)N(C)C)CCN(CC1)CCC1(O)C1=CC=C(Cl)C=C1 RDOIQAHITMMDAJ-UHFFFAOYSA-N 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 238000002961 luciferase induction Methods 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
• 239000001095 magnesium carbonate Substances 0.000 description 1
• 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
• 229960001708 magnesium carbonate Drugs 0.000 description 1
• 235000014380 magnesium carbonate Nutrition 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 229940057948 magnesium stearate Drugs 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• 230000010534 mechanism of action Effects 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 1
• 229960004640 memantine Drugs 0.000 description 1
• 230000006984 memory degeneration Effects 0.000 description 1
• 208000023060 memory loss Diseases 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 210000001589 microsome Anatomy 0.000 description 1
• 230000005012 migration Effects 0.000 description 1
• 238000013508 migration Methods 0.000 description 1
• 208000012268 mitochondrial disease Diseases 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
• 239000012046 mixed solvent Substances 0.000 description 1
• 229960001165 modafinil Drugs 0.000 description 1
• 229950007856 mofetil Drugs 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 210000002161 motor neuron Anatomy 0.000 description 1
• 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 1
• 229960004866 mycophenolate mofetil Drugs 0.000 description 1
• 210000005012 myelin Anatomy 0.000 description 1
• 230000023105 myelination Effects 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
• 229960005027 natalizumab Drugs 0.000 description 1
• 230000000926 neurological effect Effects 0.000 description 1
• 230000016273 neuron death Effects 0.000 description 1
• 230000003961 neuronal insult Effects 0.000 description 1
• 230000004112 neuroprotection Effects 0.000 description 1
• 239000002581 neurotoxin Substances 0.000 description 1
• 231100000618 neurotoxin Toxicity 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 230000003448 neutrophilic effect Effects 0.000 description 1
• 229960002715 nicotine Drugs 0.000 description 1
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
• 150000002829 nitrogen Chemical class 0.000 description 1
• 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
• 239000002767 noradrenalin uptake inhibitor Substances 0.000 description 1
• 229960002748 norepinephrine Drugs 0.000 description 1
• SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
• 229960001158 nortriptyline Drugs 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 235000019198 oils Nutrition 0.000 description 1
• 210000004248 oligodendroglia Anatomy 0.000 description 1
• 231100000822 oral exposure Toxicity 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• RYDICHIKLKVOEJ-UHFFFAOYSA-N oxadiazepine Chemical compound O1C=CC=CN=N1 RYDICHIKLKVOEJ-UHFFFAOYSA-N 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 208000010403 panophthalmitis Diseases 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 102000045222 parkin Human genes 0.000 description 1
• 229960002296 paroxetine Drugs 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 239000001814 pectin Substances 0.000 description 1
• 235000010987 pectin Nutrition 0.000 description 1
• 229920001277 pectin Polymers 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 230000010412 perfusion Effects 0.000 description 1
• 229960004851 pergolide Drugs 0.000 description 1
• YYPWGCZOLGTTER-MZMPZRCHSA-N pergolide Chemical compound C1=CC=C2[C@H]3C[C@@H](CSC)CN(CCC)[C@@H]3CC3=CN=C1[C]32 YYPWGCZOLGTTER-MZMPZRCHSA-N 0.000 description 1
• 238000005502 peroxidation Methods 0.000 description 1
• 230000002085 persistent effect Effects 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• CMCWWLVWPDLCRM-UHFFFAOYSA-N phenidone Chemical compound N1C(=O)CCN1C1=CC=CC=C1 CMCWWLVWPDLCRM-UHFFFAOYSA-N 0.000 description 1
• 208000019899 phobic disease Diseases 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 125000003386 piperidinyl group Chemical group 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
• 239000000902 placebo Substances 0.000 description 1
• 229940068196 placebo Drugs 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 229920001993 poloxamer 188 Polymers 0.000 description 1
• 229920000136 polysorbate Polymers 0.000 description 1
• 229940068965 polysorbates Drugs 0.000 description 1
• 229920002451 polyvinyl alcohol Polymers 0.000 description 1
• 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
• 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 230000001144 postural effect Effects 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 229960003089 pramipexole Drugs 0.000 description 1
• FASDKYOPVNHBLU-ZETCQYMHSA-N pramipexole Chemical compound C1[C@@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-ZETCQYMHSA-N 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 239000002243 precursor Substances 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
• 229960005205 prednisolone Drugs 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 239000000651 prodrug Substances 0.000 description 1
• 229940002612 prodrug Drugs 0.000 description 1
• 230000007101 progressive neurodegeneration Effects 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 210000004129 prosencephalon Anatomy 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 230000009979 protective mechanism Effects 0.000 description 1
• 229960002601 protriptyline Drugs 0.000 description 1
• BWPIARFWQZKAIA-UHFFFAOYSA-N protriptyline Chemical compound C1=CC2=CC=CC=C2C(CCCNC)C2=CC=CC=C21 BWPIARFWQZKAIA-UHFFFAOYSA-N 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 125000001422 pyrrolinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• GJAWHXHKYYXBSV-UHFFFAOYSA-N quinolinic acid Chemical compound OC(=O)C1=CC=CN=C1C(O)=O GJAWHXHKYYXBSV-UHFFFAOYSA-N 0.000 description 1
• 229940038850 rebif Drugs 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 230000008929 regeneration Effects 0.000 description 1
• 238000011069 regeneration method Methods 0.000 description 1
• 238000002271 resection Methods 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 229940072169 rilutek Drugs 0.000 description 1
• 229960004136 rivastigmine Drugs 0.000 description 1
• 238000011808 rodent model Methods 0.000 description 1
• 229960001879 ropinirole Drugs 0.000 description 1
• UHSKFQJFRQCDBE-UHFFFAOYSA-N ropinirole Chemical compound CCCN(CCC)CCC1=CC=CC2=C1CC(=O)N2 UHSKFQJFRQCDBE-UHFFFAOYSA-N 0.000 description 1
• 229960004586 rosiglitazone Drugs 0.000 description 1
• 229940080817 rotenone Drugs 0.000 description 1
• JUVIOZPCNVVQFO-UHFFFAOYSA-N rotenone Natural products O1C2=C3CC(C(C)=C)OC3=CC=C2C(=O)C2C1COC1=C2C=C(OC)C(OC)=C1 JUVIOZPCNVVQFO-UHFFFAOYSA-N 0.000 description 1
• 102220020162 rs397508045 Human genes 0.000 description 1
• 229910052707 ruthenium Inorganic materials 0.000 description 1
• 238000005070 sampling Methods 0.000 description 1
• HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
• MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 description 1
• 229960003946 selegiline Drugs 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
• 229960002073 sertraline Drugs 0.000 description 1
• 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 1
• 230000001568 sexual effect Effects 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 208000019116 sleep disease Diseases 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 239000011775 sodium fluoride Substances 0.000 description 1
• 235000013024 sodium fluoride Nutrition 0.000 description 1
• DUYSYHSSBDVJSM-KRWOKUGFSA-N sphingosine 1-phosphate Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)COP(O)(O)=O DUYSYHSSBDVJSM-KRWOKUGFSA-N 0.000 description 1
• 238000013222 sprague-dawley male rat Methods 0.000 description 1
• 208000024794 sputum Diseases 0.000 description 1
• 210000003802 sputum Anatomy 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 230000035882 stress Effects 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 210000003523 substantia nigra Anatomy 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 230000004083 survival effect Effects 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 230000007470 synaptic degeneration Effects 0.000 description 1
• 230000000946 synaptic effect Effects 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 229960001685 tacrine Drugs 0.000 description 1
• YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 229940033134 talc Drugs 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 229960000331 teriflunomide Drugs 0.000 description 1
• 150000003505 terpenes Chemical group 0.000 description 1
• 235000007586 terpenes Nutrition 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 238000011285 therapeutic regimen Methods 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 229940094937 thioredoxin Drugs 0.000 description 1
• 230000000451 tissue damage Effects 0.000 description 1
• 231100000827 tissue damage Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 231100000027 toxicology Toxicity 0.000 description 1
• 239000003053 toxin Substances 0.000 description 1
• 231100000765 toxin Toxicity 0.000 description 1
• 108700012359 toxins Proteins 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 238000001890 transfection Methods 0.000 description 1
• 230000009261 transgenic effect Effects 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
• 229960001032 trihexyphenidyl Drugs 0.000 description 1
• 229960002431 trimipramine Drugs 0.000 description 1
• ZSCDBOWYZJWBIY-UHFFFAOYSA-N trimipramine Chemical compound C1CC2=CC=CC=C2N(CC(CN(C)C)C)C2=CC=CC=C21 ZSCDBOWYZJWBIY-UHFFFAOYSA-N 0.000 description 1
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
• 229940079023 tysabri Drugs 0.000 description 1
• 229960004688 venlafaxine Drugs 0.000 description 1
• PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 1
• 239000013603 viral vector Substances 0.000 description 1
• 235000019165 vitamin E Nutrition 0.000 description 1
• 229940046009 vitamin E Drugs 0.000 description 1
• 239000011709 vitamin E Substances 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 239000002676 xenobiotic agent Substances 0.000 description 1
• 230000002034 xenobiotic effect Effects 0.000 description 1