CA2642647A1

CA2642647A1 - Compositions and methods for treatment of disorders of protein aggregation

Compositions and methods for treatment of disorders of protein aggregation Download PDF

Info

Publication number: CA2642647A1
Authority: CA; Canada
Prior art keywords: epi; disease; compound; pharmaceutical composition; amyloid
Prior art date: 2006-02-17
Legal status : Abandoned

Application number

CA002642647A

Other languages

English (en)

French (fr)

Inventor

Joanne Mclaurin

Current Assignee

Individual

Original Assignee

Individual

Priority date

2006-02-17

Filing date

2007-02-16

Publication date

2007-11-15

2007-02-16 Application filed by Individual filed Critical Individual

2007-11-15 Publication of CA2642647A1 publication Critical patent/CA2642647A1/en

Status Abandoned legal-status Critical Current

Links

208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 186
238000011282 treatment Methods 0.000 title claims abstract description 128
238000000034 method Methods 0.000 title claims abstract description 98
230000004845 protein aggregation Effects 0.000 title claims abstract description 18
208000035475 disorder Diseases 0.000 title claims description 64
239000000203 mixture Substances 0.000 title abstract description 154
-1 epi-inositol compound Chemical class 0.000 claims abstract description 258
CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 claims abstract description 213
201000010099 disease Diseases 0.000 claims abstract description 114
208000024827 Alzheimer disease Diseases 0.000 claims abstract description 90
230000009286 beneficial effect Effects 0.000 claims abstract description 79
230000003941 amyloidogenesis Effects 0.000 claims abstract description 53
238000009825 accumulation Methods 0.000 claims abstract description 40
238000004220 aggregation Methods 0.000 claims abstract description 34
208000010877 cognitive disease Diseases 0.000 claims abstract description 29
230000002688 persistence Effects 0.000 claims abstract description 25
230000012846 protein folding Effects 0.000 claims abstract description 19
230000007082 Aβ accumulation Effects 0.000 claims abstract description 18
208000027061 mild cognitive impairment Diseases 0.000 claims abstract description 12
150000001875 compounds Chemical class 0.000 claims description 120
239000008194 pharmaceutical composition Substances 0.000 claims description 48
230000009467 reduction Effects 0.000 claims description 46
239000003937 drug carrier Substances 0.000 claims description 45
239000000546 pharmaceutical excipient Substances 0.000 claims description 44
239000003981 vehicle Substances 0.000 claims description 42
150000003839 salts Chemical class 0.000 claims description 38
125000000217 alkyl group Chemical group 0.000 claims description 37
108090000765 processed proteins & peptides Proteins 0.000 claims description 37
230000002459 sustained effect Effects 0.000 claims description 31
230000001965 increasing effect Effects 0.000 claims description 29
239000003814 drug Substances 0.000 claims description 27
230000004083 survival effect Effects 0.000 claims description 26
108090000623 proteins and genes Proteins 0.000 claims description 24
230000001225 therapeutic effect Effects 0.000 claims description 24
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
230000015654 memory Effects 0.000 claims description 23
102000004169 proteins and genes Human genes 0.000 claims description 23
230000035508 accumulation Effects 0.000 claims description 22
125000002252 acyl group Chemical group 0.000 claims description 22
230000008021 deposition Effects 0.000 claims description 21
241000124008 Mammalia Species 0.000 claims description 18
230000003993 interaction Effects 0.000 claims description 16
230000002159 abnormal effect Effects 0.000 claims description 15
230000002776 aggregation Effects 0.000 claims description 15
125000003545 alkoxy group Chemical group 0.000 claims description 15
239000001257 hydrogen Substances 0.000 claims description 15
229910052739 hydrogen Inorganic materials 0.000 claims description 15
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 15
125000000753 cycloalkyl group Chemical group 0.000 claims description 14
125000001424 substituent group Chemical group 0.000 claims description 13
230000001988 toxicity Effects 0.000 claims description 12
231100000419 toxicity Toxicity 0.000 claims description 12
210000003169 central nervous system Anatomy 0.000 claims description 11
238000002360 preparation method Methods 0.000 claims description 11
125000003342 alkenyl group Chemical group 0.000 claims description 10
210000000056 organ Anatomy 0.000 claims description 10
102000004196 processed proteins & peptides Human genes 0.000 claims description 10
230000019771 cognition Effects 0.000 claims description 8
230000001502 supplementing effect Effects 0.000 claims description 8
230000009885 systemic effect Effects 0.000 claims description 8
229910052736 halogen Inorganic materials 0.000 claims description 7
150000002367 halogens Chemical class 0.000 claims description 7
230000005764 inhibitory process Effects 0.000 claims description 6
150000002632 lipids Chemical class 0.000 claims description 6
210000001428 peripheral nervous system Anatomy 0.000 claims description 6
229910006069 SO3H Inorganic materials 0.000 claims description 5
238000004090 dissolution Methods 0.000 claims description 4
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
230000001133 acceleration Effects 0.000 claims description 3
125000001475 halogen functional group Chemical group 0.000 claims description 3
239000000651 prodrug Substances 0.000 claims description 3
229940002612 prodrug Drugs 0.000 claims description 3
125000006823 (C1-C6) acyl group Chemical group 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
235000005911 diet Nutrition 0.000 claims description 2
230000037213 diet Effects 0.000 claims description 2
239000012634 fragment Substances 0.000 claims description 2
230000014759 maintenance of location Effects 0.000 claims description 2
230000007483 microbial process Effects 0.000 claims description 2
208000031124 Dementia Alzheimer type Diseases 0.000 claims 1
229910018828 PO3H2 Inorganic materials 0.000 claims 1
CDAISMWEOUEBRE-NIPYSYMMSA-N epi-inositol Chemical class O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](O)[C@H]1O CDAISMWEOUEBRE-NIPYSYMMSA-N 0.000 abstract description 22
241000699670 Mus sp. Species 0.000 description 127
230000000694 effects Effects 0.000 description 59
CDAISMWEOUEBRE-CDRYSYESSA-N scyllo-inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O CDAISMWEOUEBRE-CDRYSYESSA-N 0.000 description 57
210000004556 brain Anatomy 0.000 description 51
235000002639 sodium chloride Nutrition 0.000 description 38
208000037259 Amyloid Plaque Diseases 0.000 description 30
230000002490 cerebral effect Effects 0.000 description 29
102000004874 Synaptophysin Human genes 0.000 description 26
108090001076 Synaptophysin Proteins 0.000 description 26
206010002022 amyloidosis Diseases 0.000 description 25
238000012360 testing method Methods 0.000 description 24
230000027928 long-term synaptic potentiation Effects 0.000 description 23
235000018102 proteins Nutrition 0.000 description 21
208000024891 symptom Diseases 0.000 description 20
241001465754 Metazoa Species 0.000 description 19
229960000367 inositol Drugs 0.000 description 19
230000002829 reductive effect Effects 0.000 description 19
239000013589 supplement Substances 0.000 description 19
CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical class O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 18
230000000069 prophylactic effect Effects 0.000 description 18
235000015872 dietary supplement Nutrition 0.000 description 16
230000002265 prevention Effects 0.000 description 16
230000003977 synaptic function Effects 0.000 description 16
206010012289 Dementia Diseases 0.000 description 15
125000003118 aryl group Chemical group 0.000 description 15
125000004432 carbon atom Chemical group C* 0.000 description 15
239000000126 substance Substances 0.000 description 15
230000002354 daily effect Effects 0.000 description 14
238000009472 formulation Methods 0.000 description 14
230000001771 impaired effect Effects 0.000 description 14
238000002560 therapeutic procedure Methods 0.000 description 14
238000004458 analytical method Methods 0.000 description 13
230000003542 behavioural effect Effects 0.000 description 13
230000007171 neuropathology Effects 0.000 description 13
150000001413 amino acids Chemical group 0.000 description 12
150000001720 carbohydrates Chemical class 0.000 description 12
235000014633 carbohydrates Nutrition 0.000 description 12
210000004027 cell Anatomy 0.000 description 12
230000002401 inhibitory effect Effects 0.000 description 12
206010018341 Gliosis Diseases 0.000 description 11
235000001014 amino acid Nutrition 0.000 description 11
229940024606 amino acid Drugs 0.000 description 11
230000006999 cognitive decline Effects 0.000 description 11
DSCFFEYYQKSRSV-UHFFFAOYSA-N 1L-O1-methyl-muco-inositol Natural products COC1C(O)C(O)C(O)C(O)C1O DSCFFEYYQKSRSV-UHFFFAOYSA-N 0.000 description 10
108010090849 Amyloid beta-Peptides Proteins 0.000 description 10
102000013455 Amyloid beta-Peptides Human genes 0.000 description 10
VJXUJFAZXQOXMJ-UHFFFAOYSA-N D-1-O-Methyl-muco-inositol Natural products CC12C(OC)(C)OC(C)(C)C2CC(=O)C(C23OC2C(=O)O2)(C)C1CCC3(C)C2C=1C=COC=1 VJXUJFAZXQOXMJ-UHFFFAOYSA-N 0.000 description 10
238000000540 analysis of variance Methods 0.000 description 10
229940079593 drug Drugs 0.000 description 10
230000002518 glial effect Effects 0.000 description 10
230000004054 inflammatory process Effects 0.000 description 10
239000007788 liquid Substances 0.000 description 10
230000002792 vascular Effects 0.000 description 10
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 9
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 9
239000003795 chemical substances by application Substances 0.000 description 9
125000000623 heterocyclic group Chemical group 0.000 description 9
210000001320 hippocampus Anatomy 0.000 description 9
150000003254 radicals Chemical class 0.000 description 9
102000009091 Amyloidogenic Proteins Human genes 0.000 description 8
108010048112 Amyloidogenic Proteins Proteins 0.000 description 8
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
206010061218 Inflammation Diseases 0.000 description 8
208000037875 astrocytosis Diseases 0.000 description 8
230000007341 astrogliosis Effects 0.000 description 8
230000006399 behavior Effects 0.000 description 8
239000002775 capsule Substances 0.000 description 8
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
230000007423 decrease Effects 0.000 description 8
125000001072 heteroaryl group Chemical group 0.000 description 8
238000001727 in vivo Methods 0.000 description 8
239000003112 inhibitor Substances 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
238000012423 maintenance Methods 0.000 description 8
235000012054 meals Nutrition 0.000 description 8
150000002772 monosaccharides Chemical class 0.000 description 8
229920000642 polymer Polymers 0.000 description 8
230000002035 prolonged effect Effects 0.000 description 8
239000000243 solution Substances 0.000 description 8
DSCFFEYYQKSRSV-KLJZZCKASA-N D-pinitol Chemical group CO[C@@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@H]1O DSCFFEYYQKSRSV-KLJZZCKASA-N 0.000 description 7
208000018737 Parkinson disease Diseases 0.000 description 7
239000000654 additive Substances 0.000 description 7
230000007278 cognition impairment Effects 0.000 description 7
230000003247 decreasing effect Effects 0.000 description 7
238000010172 mouse model Methods 0.000 description 7
230000004770 neurodegeneration Effects 0.000 description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 7
239000000523 sample Substances 0.000 description 7
239000007787 solid Substances 0.000 description 7
239000000829 suppository Substances 0.000 description 7
125000005309 thioalkoxy group Chemical group 0.000 description 7
238000012549 training Methods 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 6
108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 6
238000012347 Morris Water Maze Methods 0.000 description 6
208000001089 Multiple system atrophy Diseases 0.000 description 6
241000699666 Mus <mouse, genus> Species 0.000 description 6
206010035226 Plasma cell myeloma Diseases 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 6
229930006000 Sucrose Natural products 0.000 description 6
230000008901 benefit Effects 0.000 description 6
MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 6
125000004181 carboxyalkyl group Chemical group 0.000 description 6
230000003920 cognitive function Effects 0.000 description 6
125000004093 cyano group Chemical group *C#N 0.000 description 6
230000006735 deficit Effects 0.000 description 6
230000003111 delayed effect Effects 0.000 description 6
239000000839 emulsion Substances 0.000 description 6
238000002474 experimental method Methods 0.000 description 6
239000008103 glucose Substances 0.000 description 6
239000008187 granular material Substances 0.000 description 6
230000003370 grooming effect Effects 0.000 description 6
125000005843 halogen group Chemical group 0.000 description 6
235000006486 human diet Nutrition 0.000 description 6
239000002609 medium Substances 0.000 description 6
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
230000007388 microgliosis Effects 0.000 description 6
230000004048 modification Effects 0.000 description 6
238000012986 modification Methods 0.000 description 6
208000015122 neurodegenerative disease Diseases 0.000 description 6
230000002981 neuropathic effect Effects 0.000 description 6
238000012346 open field test Methods 0.000 description 6
230000004044 response Effects 0.000 description 6
239000005720 sucrose Substances 0.000 description 6
235000000346 sugar Nutrition 0.000 description 6
230000000946 synaptic effect Effects 0.000 description 6
125000003396 thiol group Chemical class [H]S* 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
206010002023 Amyloidoses Diseases 0.000 description 5
208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 5
241000282412 Homo Species 0.000 description 5
229930194542 Keto Natural products 0.000 description 5
229920002472 Starch Polymers 0.000 description 5
239000004480 active ingredient Substances 0.000 description 5
125000000033 alkoxyamino group Chemical group 0.000 description 5
238000003556 assay Methods 0.000 description 5
239000006172 buffering agent Substances 0.000 description 5
239000000969 carrier Substances 0.000 description 5
208000037976 chronic inflammation Diseases 0.000 description 5
238000011284 combination treatment Methods 0.000 description 5
230000006870 function Effects 0.000 description 5
125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 5
230000006872 improvement Effects 0.000 description 5
238000000338 in vitro Methods 0.000 description 5
125000000468 ketone group Chemical group 0.000 description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
241000894007 species Species 0.000 description 5
235000019698 starch Nutrition 0.000 description 5
239000000725 suspension Substances 0.000 description 5
239000006188 syrup Substances 0.000 description 5
235000020357 syrup Nutrition 0.000 description 5
239000003826 tablet Substances 0.000 description 5
229940124597 therapeutic agent Drugs 0.000 description 5
125000005323 thioketone group Chemical group 0.000 description 5
208000001072 type 2 diabetes mellitus Diseases 0.000 description 5
229960005486 vaccine Drugs 0.000 description 5
230000009184 walking Effects 0.000 description 5
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 4
208000003808 Amyloid Neuropathies Diseases 0.000 description 4
206010059245 Angiopathy Diseases 0.000 description 4
208000028698 Cognitive impairment Diseases 0.000 description 4
208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 4
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
150000008574 D-amino acids Chemical class 0.000 description 4
201000010374 Down Syndrome Diseases 0.000 description 4
102000004190 Enzymes Human genes 0.000 description 4
108090000790 Enzymes Proteins 0.000 description 4
201000011240 Frontotemporal dementia Diseases 0.000 description 4
108010010803 Gelatin Proteins 0.000 description 4
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
101000823051 Homo sapiens Amyloid-beta precursor protein Proteins 0.000 description 4
208000023105 Huntington disease Diseases 0.000 description 4
201000000162 ITM2B-related cerebral amyloid angiopathy 1 Diseases 0.000 description 4
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 4
201000002832 Lewy body dementia Diseases 0.000 description 4
229930195725 Mannitol Natural products 0.000 description 4
102000029797 Prion Human genes 0.000 description 4
108091000054 Prion Proteins 0.000 description 4
208000024777 Prion disease Diseases 0.000 description 4
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
239000013543 active substance Substances 0.000 description 4
230000000996 additive effect Effects 0.000 description 4
238000013459 approach Methods 0.000 description 4
239000011230 binding agent Substances 0.000 description 4
230000033228 biological regulation Effects 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
230000037396 body weight Effects 0.000 description 4
208000006752 brain edema Diseases 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
210000005056 cell body Anatomy 0.000 description 4
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
230000001684 chronic effect Effects 0.000 description 4
239000003636 conditioned culture medium Substances 0.000 description 4
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 4
230000004064 dysfunction Effects 0.000 description 4
229940088598 enzyme Drugs 0.000 description 4
235000019441 ethanol Nutrition 0.000 description 4
125000000524 functional group Chemical group 0.000 description 4
239000008273 gelatin Substances 0.000 description 4
229920000159 gelatin Polymers 0.000 description 4
235000019322 gelatine Nutrition 0.000 description 4
235000011852 gelatine desserts Nutrition 0.000 description 4
239000001963 growth medium Substances 0.000 description 4
210000005154 hemibrain Anatomy 0.000 description 4
150000002402 hexoses Chemical class 0.000 description 4
239000008101 lactose Substances 0.000 description 4
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
239000000594 mannitol Substances 0.000 description 4
235000010355 mannitol Nutrition 0.000 description 4
238000007911 parenteral administration Methods 0.000 description 4
230000001575 pathological effect Effects 0.000 description 4
230000007170 pathology Effects 0.000 description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
239000006187 pill Substances 0.000 description 4
230000008569 process Effects 0.000 description 4
230000000750 progressive effect Effects 0.000 description 4
238000011321 prophylaxis Methods 0.000 description 4
208000020016 psychiatric disease Diseases 0.000 description 4
230000009257 reactivity Effects 0.000 description 4
230000002441 reversible effect Effects 0.000 description 4
230000006403 short-term memory Effects 0.000 description 4
239000008107 starch Substances 0.000 description 4
229940032147 starch Drugs 0.000 description 4
125000005346 substituted cycloalkyl group Chemical group 0.000 description 4
238000013268 sustained release Methods 0.000 description 4
239000012730 sustained-release form Substances 0.000 description 4
230000032258 transport Effects 0.000 description 4
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 4
230000031836 visual learning Effects 0.000 description 4
238000001262 western blot Methods 0.000 description 4
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 3
208000023697 ABri amyloidosis Diseases 0.000 description 3
102000014461 Ataxins Human genes 0.000 description 3
108010078286 Ataxins Proteins 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
201000009030 Carcinoma Diseases 0.000 description 3
206010008025 Cerebellar ataxia Diseases 0.000 description 3
208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 3
206010067889 Dementia with Lewy bodies Diseases 0.000 description 3
238000002965 ELISA Methods 0.000 description 3
206010016207 Familial Mediterranean fever Diseases 0.000 description 3
102000003886 Glycoproteins Human genes 0.000 description 3
108090000288 Glycoproteins Proteins 0.000 description 3
229920002683 Glycosaminoglycan Polymers 0.000 description 3
208000005531 Immunoglobulin Light-chain Amyloidosis Diseases 0.000 description 3
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
150000008575 L-amino acids Chemical class 0.000 description 3
206010028980 Neoplasm Diseases 0.000 description 3
206010029350 Neurotoxicity Diseases 0.000 description 3
239000000020 Nitrocellulose Substances 0.000 description 3
108091000080 Phosphotransferase Proteins 0.000 description 3
208000000609 Pick Disease of the Brain Diseases 0.000 description 3
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
208000009415 Spinocerebellar Ataxias Diseases 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
206010044221 Toxic encephalopathy Diseases 0.000 description 3
102100029290 Transthyretin Human genes 0.000 description 3
239000002253 acid Substances 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
230000009471 action Effects 0.000 description 3
125000004442 acylamino group Chemical group 0.000 description 3
125000004423 acyloxy group Chemical group 0.000 description 3
230000032683 aging Effects 0.000 description 3
125000000266 alpha-aminoacyl group Chemical group 0.000 description 3
230000004075 alteration Effects 0.000 description 3
150000001408 amides Chemical class 0.000 description 3
PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 3
125000004104 aryloxy group Chemical group 0.000 description 3
210000001130 astrocyte Anatomy 0.000 description 3
201000004562 autosomal dominant cerebellar ataxia Diseases 0.000 description 3
239000002585 base Substances 0.000 description 3
XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 3
230000027455 binding Effects 0.000 description 3
210000001124 body fluid Anatomy 0.000 description 3
239000010839 body fluid Substances 0.000 description 3
230000007541 cellular toxicity Effects 0.000 description 3
125000001309 chloro group Chemical group Cl* 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
230000003931 cognitive performance Effects 0.000 description 3
239000003086 colorant Substances 0.000 description 3
FGFCSHCXBYAKOL-UHFFFAOYSA-N cyclohexane-1,1,2,2,3,3-hexol Chemical class OC1(O)CCCC(O)(O)C1(O)O FGFCSHCXBYAKOL-UHFFFAOYSA-N 0.000 description 3
230000034994 death Effects 0.000 description 3
231100000517 death Toxicity 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
150000002016 disaccharides Chemical class 0.000 description 3
238000009826 distribution Methods 0.000 description 3
230000002708 enhancing effect Effects 0.000 description 3
206010015037 epilepsy Diseases 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
230000035557 fibrillogenesis Effects 0.000 description 3
125000001153 fluoro group Chemical group F* 0.000 description 3
235000019253 formic acid Nutrition 0.000 description 3
239000007903 gelatin capsule Substances 0.000 description 3
230000007387 gliosis Effects 0.000 description 3
150000004676 glycans Chemical class 0.000 description 3
235000011187 glycerol Nutrition 0.000 description 3
238000001631 haemodialysis Methods 0.000 description 3
210000002216 heart Anatomy 0.000 description 3
230000000322 hemodialysis Effects 0.000 description 3
230000000971 hippocampal effect Effects 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
238000002649 immunization Methods 0.000 description 3
230000003053 immunization Effects 0.000 description 3
238000007912 intraperitoneal administration Methods 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
238000002372 labelling Methods 0.000 description 3
239000000314 lubricant Substances 0.000 description 3
210000002540 macrophage Anatomy 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
230000007246 mechanism Effects 0.000 description 3
230000001404 mediated effect Effects 0.000 description 3
230000004060 metabolic process Effects 0.000 description 3
229920000609 methyl cellulose Polymers 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
239000001923 methylcellulose Substances 0.000 description 3
235000010981 methylcellulose Nutrition 0.000 description 3
208000005264 motor neuron disease Diseases 0.000 description 3
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 3
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
125000001624 naphthyl group Chemical group 0.000 description 3
239000013642 negative control Substances 0.000 description 3
230000007135 neurotoxicity Effects 0.000 description 3
231100000228 neurotoxicity Toxicity 0.000 description 3
229920001220 nitrocellulos Polymers 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
229920001542 oligosaccharide Polymers 0.000 description 3
150000002482 oligosaccharides Chemical class 0.000 description 3
239000000816 peptidomimetic Substances 0.000 description 3
230000002093 peripheral effect Effects 0.000 description 3
102000020233 phosphotransferase Human genes 0.000 description 3
229920001282 polysaccharide Polymers 0.000 description 3
239000005017 polysaccharide Substances 0.000 description 3
229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
239000001267 polyvinylpyrrolidone Substances 0.000 description 3
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
208000022256 primary systemic amyloidosis Diseases 0.000 description 3
210000002966 serum Anatomy 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
238000007920 subcutaneous administration Methods 0.000 description 3
125000000547 substituted alkyl group Chemical group 0.000 description 3
125000003107 substituted aryl group Chemical group 0.000 description 3
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 3
150000003462 sulfoxides Chemical class 0.000 description 3
230000002195 synergetic effect Effects 0.000 description 3
231100000331 toxic Toxicity 0.000 description 3
230000002588 toxic effect Effects 0.000 description 3
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
ZSTLCHCDLIUXJE-ZGBAEQJLSA-N (2S,5S)-2-methylspiro[1,3-oxathiolane-5,3'-1-azabicyclo[2.2.2]octane] hydrate dihydrochloride Chemical compound O.Cl.Cl.C1S[C@@H](C)O[C@@]21C(CC1)CCN1C2.C1S[C@@H](C)O[C@@]21C(CC1)CCN1C2 ZSTLCHCDLIUXJE-ZGBAEQJLSA-N 0.000 description 2
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
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 2
MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
208000023769 AA amyloidosis Diseases 0.000 description 2
108010088751 Albumins Proteins 0.000 description 2
102000009027 Albumins Human genes 0.000 description 2
208000007848 Alcoholism Diseases 0.000 description 2
235000019489 Almond oil Nutrition 0.000 description 2
102000001049 Amyloid Human genes 0.000 description 2
108010094108 Amyloid Proteins 0.000 description 2
101710137189 Amyloid-beta A4 protein Proteins 0.000 description 2
101710151993 Amyloid-beta precursor protein Proteins 0.000 description 2
102100022704 Amyloid-beta precursor protein Human genes 0.000 description 2
208000019901 Anxiety disease Diseases 0.000 description 2
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
102000007371 Ataxin-3 Human genes 0.000 description 2
241000894006 Bacteria Species 0.000 description 2
BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
208000005145 Cerebral amyloid angiopathy Diseases 0.000 description 2
206010008111 Cerebral haemorrhage Diseases 0.000 description 2
208000035473 Communicable disease Diseases 0.000 description 2
206010010904 Convulsion Diseases 0.000 description 2
WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 2
HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 2
SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
201000008163 Dentatorubral pallidoluysian atrophy Diseases 0.000 description 2
241000588724 Escherichia coli Species 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
208000003736 Gerstmann-Straussler-Scheinker Disease Diseases 0.000 description 2
239000004471 Glycine Substances 0.000 description 2
229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 2
SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 2
206010020772 Hypertension Diseases 0.000 description 2
HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
102100021496 Insulin-degrading enzyme Human genes 0.000 description 2
108090000828 Insulysin Proteins 0.000 description 2
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
WQZGKKKJIJFFOK-VSOAQEOCSA-N L-altropyranose Chemical compound OC[C@@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-VSOAQEOCSA-N 0.000 description 2
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
235000010643 Leucaena leucocephala Nutrition 0.000 description 2
240000007472 Leucaena leucocephala Species 0.000 description 2
208000002569 Machado-Joseph Disease Diseases 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
102000005431 Molecular Chaperones Human genes 0.000 description 2
108010006519 Molecular Chaperones Proteins 0.000 description 2
PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 2
208000026072 Motor neurone disease Diseases 0.000 description 2
208000034578 Multiple myelomas Diseases 0.000 description 2
102000003729 Neprilysin Human genes 0.000 description 2
108090000028 Neprilysin Proteins 0.000 description 2
102000012404 Orosomucoid Human genes 0.000 description 2
108010061952 Orosomucoid Proteins 0.000 description 2
206010033892 Paraplegia Diseases 0.000 description 2
208000002774 Paraproteinemias Diseases 0.000 description 2
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
206010062519 Poor quality sleep Diseases 0.000 description 2
108010071690 Prealbumin Proteins 0.000 description 2
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
208000028017 Psychotic disease Diseases 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
206010037660 Pyrexia Diseases 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 2
RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 2
206010039811 Secondary amyloidosis Diseases 0.000 description 2
102000054727 Serum Amyloid A Human genes 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
208000032930 Spastic paraplegia Diseases 0.000 description 2
208000036834 Spinocerebellar ataxia type 3 Diseases 0.000 description 2
PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
102000019355 Synuclein Human genes 0.000 description 2
108050006783 Synuclein Proteins 0.000 description 2
208000032859 Synucleinopathies Diseases 0.000 description 2
208000003217 Tetany Diseases 0.000 description 2
DGDCHPCRMWEOJR-FQPOAREZSA-N Thr-Ala-Tyr Chemical group C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 DGDCHPCRMWEOJR-FQPOAREZSA-N 0.000 description 2
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
239000004473 Threonine Substances 0.000 description 2
108700019146 Transgenes Proteins 0.000 description 2
206010044688 Trisomy 21 Diseases 0.000 description 2
NOXKHHXSHQFSGJ-FQPOAREZSA-N Tyr-Ala-Thr Chemical group C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 NOXKHHXSHQFSGJ-FQPOAREZSA-N 0.000 description 2
208000018756 Variant Creutzfeldt-Jakob disease Diseases 0.000 description 2
DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
230000004913 activation Effects 0.000 description 2
239000000443 aerosol Substances 0.000 description 2
230000004931 aggregating effect Effects 0.000 description 2
235000004279 alanine Nutrition 0.000 description 2
201000007930 alcohol dependence Diseases 0.000 description 2
239000008168 almond oil Substances 0.000 description 2
HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 2
DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 2
206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
208000022531 anorexia Diseases 0.000 description 2
239000003963 antioxidant agent Substances 0.000 description 2
235000006708 antioxidants Nutrition 0.000 description 2
230000036506 anxiety Effects 0.000 description 2
239000007900 aqueous suspension Substances 0.000 description 2
PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 2
150000005840 aryl radicals Chemical class 0.000 description 2
229960001230 asparagine Drugs 0.000 description 2
235000009582 asparagine Nutrition 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
230000037424 autonomic function Effects 0.000 description 2
230000006736 behavioral deficit Effects 0.000 description 2
229940049706 benzodiazepine Drugs 0.000 description 2
125000003310 benzodiazepinyl group Chemical group N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
230000000903 blocking effect Effects 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
239000008280 blood Substances 0.000 description 2
230000008499 blood brain barrier function Effects 0.000 description 2
210000001218 blood-brain barrier Anatomy 0.000 description 2
125000001246 bromo group Chemical group Br* 0.000 description 2
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
235000019577 caloric intake Nutrition 0.000 description 2
201000011510 cancer Diseases 0.000 description 2
239000007894 caplet Substances 0.000 description 2
239000004202 carbamide Substances 0.000 description 2
230000015556 catabolic process Effects 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
235000010980 cellulose Nutrition 0.000 description 2
230000008859 change Effects 0.000 description 2
210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
235000012000 cholesterol Nutrition 0.000 description 2
230000006020 chronic inflammation Effects 0.000 description 2
208000037893 chronic inflammatory disorder Diseases 0.000 description 2
238000002648 combination therapy Methods 0.000 description 2
JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
230000002596 correlated effect Effects 0.000 description 2
CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 2
230000001186 cumulative effect Effects 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
125000000392 cycloalkenyl group Chemical group 0.000 description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
XVOYSCVBGLVSOL-UHFFFAOYSA-N cysteic acid Chemical compound OC(=O)C(N)CS(O)(=O)=O XVOYSCVBGLVSOL-UHFFFAOYSA-N 0.000 description 2
230000003013 cytotoxicity Effects 0.000 description 2
231100000135 cytotoxicity Toxicity 0.000 description 2
206010061428 decreased appetite Diseases 0.000 description 2
230000002950 deficient Effects 0.000 description 2
238000006731 degradation reaction Methods 0.000 description 2
208000017004 dementia pugilistica Diseases 0.000 description 2
230000006866 deterioration Effects 0.000 description 2
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
239000002270 dispersing agent Substances 0.000 description 2
239000003651 drinking water Substances 0.000 description 2
235000020188 drinking water Nutrition 0.000 description 2
238000009510 drug design Methods 0.000 description 2
230000008482 dysregulation Effects 0.000 description 2
239000003995 emulsifying agent Substances 0.000 description 2
206010014599 encephalitis Diseases 0.000 description 2
230000037149 energy metabolism Effects 0.000 description 2
230000002255 enzymatic effect Effects 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
208000001759 familial encephalopathy with neuroserpin inclusion bodies Diseases 0.000 description 2
230000002349 favourable effect Effects 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
235000013355 food flavoring agent Nutrition 0.000 description 2
230000037406 food intake Effects 0.000 description 2
235000012631 food intake Nutrition 0.000 description 2
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
229930182830 galactose Natural products 0.000 description 2
150000002270 gangliosides Chemical class 0.000 description 2
210000001035 gastrointestinal tract Anatomy 0.000 description 2
238000001415 gene therapy Methods 0.000 description 2
229960002442 glucosamine Drugs 0.000 description 2
150000002337 glycosamines Chemical class 0.000 description 2
230000012010 growth Effects 0.000 description 2
125000004438 haloalkoxy group Chemical group 0.000 description 2
LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 2
125000005553 heteroaryloxy group Chemical group 0.000 description 2
125000005842 heteroatom Chemical group 0.000 description 2
125000004470 heterocyclooxy group Chemical group 0.000 description 2
150000004000 hexols Chemical class 0.000 description 2
230000003284 homeostatic effect Effects 0.000 description 2
230000003054 hormonal effect Effects 0.000 description 2
102000046783 human APP Human genes 0.000 description 2
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
229960001680 ibuprofen Drugs 0.000 description 2
238000009169 immunotherapy Methods 0.000 description 2
210000003000 inclusion body Anatomy 0.000 description 2
238000011534 incubation Methods 0.000 description 2
208000015181 infectious disease Diseases 0.000 description 2
230000028709 inflammatory response Effects 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
208000019715 inherited Creutzfeldt-Jakob disease Diseases 0.000 description 2
150000004001 inositols Chemical class 0.000 description 2
238000007918 intramuscular administration Methods 0.000 description 2
238000002955 isolation Methods 0.000 description 2
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
210000003734 kidney Anatomy 0.000 description 2
230000003907 kidney function Effects 0.000 description 2
230000013016 learning Effects 0.000 description 2
239000000787 lecithin Substances 0.000 description 2
235000010445 lecithin Nutrition 0.000 description 2
229940067606 lecithin Drugs 0.000 description 2
230000003908 liver function Effects 0.000 description 2
238000011068 loading method Methods 0.000 description 2
230000006742 locomotor activity Effects 0.000 description 2
230000007774 longterm Effects 0.000 description 2
229960004844 lovastatin Drugs 0.000 description 2
PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 2
QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 2
239000007937 lozenge Substances 0.000 description 2
239000000463 material Substances 0.000 description 2
201000011475 meningoencephalitis Diseases 0.000 description 2
239000002207 metabolite Substances 0.000 description 2
229930182817 methionine Natural products 0.000 description 2
230000004001 molecular interaction Effects 0.000 description 2
239000000178 monomer Substances 0.000 description 2
235000019799 monosodium phosphate Nutrition 0.000 description 2
230000037023 motor activity Effects 0.000 description 2
230000035772 mutation Effects 0.000 description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
230000030523 negative regulation of long-term synaptic potentiation Effects 0.000 description 2
230000001537 neural effect Effects 0.000 description 2
201000007601 neurodegeneration with brain iron accumulation Diseases 0.000 description 2
210000002569 neuron Anatomy 0.000 description 2
231100000189 neurotoxic Toxicity 0.000 description 2
230000002887 neurotoxic effect Effects 0.000 description 2
238000006386 neutralization reaction Methods 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
239000002773 nucleotide Substances 0.000 description 2
235000016709 nutrition Nutrition 0.000 description 2
238000006384 oligomerization reaction Methods 0.000 description 2
208000031237 olivopontocerebellar atrophy Diseases 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
239000006179 pH buffering agent Substances 0.000 description 2
230000008506 pathogenesis Effects 0.000 description 2
230000001717 pathogenic effect Effects 0.000 description 2
239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 description 2
230000007505 plaque formation Effects 0.000 description 2
229920003229 poly(methyl methacrylate) Polymers 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
239000004926 polymethyl methacrylate Substances 0.000 description 2
229920001184 polypeptide Polymers 0.000 description 2
239000000843 powder Substances 0.000 description 2
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 2
238000011002 quantification Methods 0.000 description 2
230000000384 rearing effect Effects 0.000 description 2
230000000630 rising effect Effects 0.000 description 2
201000000980 schizophrenia Diseases 0.000 description 2
208000008864 scrapie Diseases 0.000 description 2
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
230000036362 sensorimotor function Effects 0.000 description 2
229960002855 simvastatin Drugs 0.000 description 2
RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 2
230000007958 sleep Effects 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 2
229910000162 sodium phosphate Inorganic materials 0.000 description 2
239000008279 sol Substances 0.000 description 2
239000002904 solvent Substances 0.000 description 2
230000006886 spatial memory Effects 0.000 description 2
230000002269 spontaneous effect Effects 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
238000007619 statistical method Methods 0.000 description 2
239000012058 sterile packaged powder Substances 0.000 description 2
230000004936 stimulating effect Effects 0.000 description 2
125000005017 substituted alkenyl group Chemical group 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
150000008163 sugars Chemical class 0.000 description 2
125000004646 sulfenyl group Chemical group S(*)* 0.000 description 2
125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 2
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
229910052717 sulfur Chemical group 0.000 description 2
239000011593 sulfur Chemical group 0.000 description 2
239000000375 suspending agent Substances 0.000 description 2
208000011580 syndromic disease Diseases 0.000 description 2
102000013498 tau Proteins Human genes 0.000 description 2
108010026424 tau Proteins Proteins 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
231100001274 therapeutic index Toxicity 0.000 description 2
150000003573 thiols Chemical class 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
230000009261 transgenic effect Effects 0.000 description 2
238000012301 transgenic model Methods 0.000 description 2
238000011830 transgenic mouse model Methods 0.000 description 2
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
230000004304 visual acuity Effects 0.000 description 2
238000009736 wetting Methods 0.000 description 2
JSPNNZKWADNWHI-PNANGNLXSA-N (2r)-2-hydroxy-n-[(2s,3r,4e,8e)-3-hydroxy-9-methyl-1-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoctadeca-4,8-dien-2-yl]heptadecanamide Chemical compound CCCCCCCCCCCCCCC[C@@H](O)C(=O)N[C@H]([C@H](O)\C=C\CC\C=C(/C)CCCCCCCCC)CO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O JSPNNZKWADNWHI-PNANGNLXSA-N 0.000 description 1
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
VYEGBDHSGHXOGT-ZLIBEWLCSA-N (2r,3s,5r,6s)-2,3,4,5,6-pentahydroxycyclohexan-1-one Chemical compound OC1[C@H](O)[C@@H](O)C(=O)[C@@H](O)[C@@H]1O VYEGBDHSGHXOGT-ZLIBEWLCSA-N 0.000 description 1
PHOZOHFUXHPOCK-QMMMGPOBSA-N (2s)-2-ethyl-8-methyl-1-thia-4,8-diazaspiro[4.5]decan-3-one Chemical compound N1C(=O)[C@H](CC)SC11CCN(C)CC1 PHOZOHFUXHPOCK-QMMMGPOBSA-N 0.000 description 1
IMGXDCAOBSTOQJ-CFTXMQDWSA-N (3R,4R,5R,6R)-3-amino-6-(hydroxymethyl)oxane-2,4,5-triol (2R,3R,4R,5R)-2-amino-3,4,5,6-tetrahydroxyhexanal Chemical compound O=C[C@H](N)[C@@H](O)[C@@H](O)[C@H](O)CO.N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O IMGXDCAOBSTOQJ-CFTXMQDWSA-N 0.000 description 1
FIARMZDBEGVMLV-UHFFFAOYSA-N 1,1,2,2,2-pentafluoroethanolate Chemical group [O-]C(F)(F)C(F)(F)F FIARMZDBEGVMLV-UHFFFAOYSA-N 0.000 description 1
DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
WIHMBLDNRMIGDW-UHFFFAOYSA-N 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-3h-2-benzofuran-5-carbonitrile;hydron;bromide Chemical compound [Br-].O1CC2=CC(C#N)=CC=C2C1(CCC[NH+](C)C)C1=CC=C(F)C=C1 WIHMBLDNRMIGDW-UHFFFAOYSA-N 0.000 description 1
OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
CDAISMWEOUEBRE-LKPKBOIGSA-N 1D-chiro-inositol Chemical compound O[C@H]1[C@@H](O)[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O CDAISMWEOUEBRE-LKPKBOIGSA-N 0.000 description 1
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
GZCGUPFRVQAUEE-UHFFFAOYSA-N 2,3,4,5,6-pentahydroxyhexanal Chemical compound OCC(O)C(O)C(O)C(O)C=O GZCGUPFRVQAUEE-UHFFFAOYSA-N 0.000 description 1
VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
VGGGBQVTSUMURJ-UHFFFAOYSA-N 2,8-dimethyl-1-thia-3,8-diazaspiro[4.5]dec-2-ene Chemical compound C1CN(C)CCC11SC(C)=NC1 VGGGBQVTSUMURJ-UHFFFAOYSA-N 0.000 description 1
125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
VLRSADZEDXVUPG-UHFFFAOYSA-N 2-naphthalen-1-ylpyridine Chemical compound N1=CC=CC=C1C1=CC=CC2=CC=CC=C12 VLRSADZEDXVUPG-UHFFFAOYSA-N 0.000 description 1
VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
AEMOLEFTQBMNLQ-UHFFFAOYSA-N 3,4,5,6-tetrahydroxyoxane-2-carboxylic acid Chemical compound OC1OC(C(O)=O)C(O)C(O)C1O AEMOLEFTQBMNLQ-UHFFFAOYSA-N 0.000 description 1
MIDXCONKKJTLDX-UHFFFAOYSA-N 3,5-dimethylcyclopentane-1,2-dione Chemical compound CC1CC(C)C(=O)C1=O MIDXCONKKJTLDX-UHFFFAOYSA-N 0.000 description 1
SNKZJIOFVMKAOJ-UHFFFAOYSA-N 3-Aminopropanesulfonate Chemical compound NCCCS(O)(=O)=O SNKZJIOFVMKAOJ-UHFFFAOYSA-N 0.000 description 1
GDRVFDDBLLKWRI-UHFFFAOYSA-N 4H-quinolizine Chemical compound C1=CC=CN2CC=CC=C21 GDRVFDDBLLKWRI-UHFFFAOYSA-N 0.000 description 1
FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
208000017227 ADan amyloidosis Diseases 0.000 description 1
208000023761 AL amyloidosis Diseases 0.000 description 1
102000012440 Acetylcholinesterase Human genes 0.000 description 1
108010022752 Acetylcholinesterase Proteins 0.000 description 1
241000251468 Actinopterygii Species 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
208000006888 Agnosia Diseases 0.000 description 1
241001047040 Agnosia Species 0.000 description 1
102000002260 Alkaline Phosphatase Human genes 0.000 description 1
108020004774 Alkaline Phosphatase Proteins 0.000 description 1
206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
101710081722 Antitrypsin Proteins 0.000 description 1
206010003062 Apraxia Diseases 0.000 description 1
240000003291 Armoracia rusticana Species 0.000 description 1
235000011330 Armoracia rusticana Nutrition 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
206010003591 Ataxia Diseases 0.000 description 1
108090001008 Avidin Proteins 0.000 description 1
238000000035 BCA protein assay Methods 0.000 description 1
208000027496 Behcet disease Diseases 0.000 description 1
208000009137 Behcet syndrome Diseases 0.000 description 1
102100026189 Beta-galactosidase Human genes 0.000 description 1
241000588832 Bordetella pertussis Species 0.000 description 1
241000589969 Borreliella burgdorferi Species 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
241000219475 Bougainvillea Species 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
241000283707 Capra Species 0.000 description 1
241000606153 Chlamydia trachomatis Species 0.000 description 1
108010062580 Concanavalin A Proteins 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
208000011990 Corticobasal Degeneration Diseases 0.000 description 1
208000011231 Crohn disease Diseases 0.000 description 1
102000013717 Cyclin-Dependent Kinase 5 Human genes 0.000 description 1
108010025454 Cyclin-Dependent Kinase 5 Proteins 0.000 description 1
YTBSYETUWUMLBZ-UHFFFAOYSA-N D-Erythrose Natural products OCC(O)C(O)C=O YTBSYETUWUMLBZ-UHFFFAOYSA-N 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
WQZGKKKJIJFFOK-CBPJZXOFSA-N D-Gulose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O WQZGKKKJIJFFOK-CBPJZXOFSA-N 0.000 description 1
WQZGKKKJIJFFOK-WHZQZERISA-N D-aldose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-WHZQZERISA-N 0.000 description 1
WQZGKKKJIJFFOK-IVMDWMLBSA-N D-allopyranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@H](O)[C@@H]1O WQZGKKKJIJFFOK-IVMDWMLBSA-N 0.000 description 1
YTBSYETUWUMLBZ-IUYQGCFVSA-N D-erythrose Chemical compound OC[C@@H](O)[C@@H](O)C=O YTBSYETUWUMLBZ-IUYQGCFVSA-N 0.000 description 1
AEMOLEFTQBMNLQ-YMDCURPLSA-N D-galactopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-YMDCURPLSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
YTBSYETUWUMLBZ-QWWZWVQMSA-N D-threose Chemical compound OC[C@@H](O)[C@H](O)C=O YTBSYETUWUMLBZ-QWWZWVQMSA-N 0.000 description 1
206010011878 Deafness Diseases 0.000 description 1
206010012218 Delirium Diseases 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 0.000 description 1
239000004338 Dichlorodifluoromethane Substances 0.000 description 1
101100511184 Dictyostelium discoideum limB gene Proteins 0.000 description 1
208000009093 Diffuse Neurofibrillary Tangles with Calcification Diseases 0.000 description 1
206010061818 Disease progression Diseases 0.000 description 1
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
241000196324 Embryophyta Species 0.000 description 1
208000001976 Endocrine Gland Neoplasms Diseases 0.000 description 1
241000283086 Equidae Species 0.000 description 1
206010056474 Erythrosis Diseases 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
108050001049 Extracellular proteins Proteins 0.000 description 1
208000034846 Familial Amyloid Neuropathies Diseases 0.000 description 1
206010016202 Familial Amyloidosis Diseases 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
108010049003 Fibrinogen Proteins 0.000 description 1
102000008946 Fibrinogen Human genes 0.000 description 1
201000007888 Finnish type amyloidosis Diseases 0.000 description 1
229930091371 Fructose Natural products 0.000 description 1
RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
239000005715 Fructose Substances 0.000 description 1
PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 1
241000233866 Fungi Species 0.000 description 1
102000001267 GSK3 Human genes 0.000 description 1
108060006662 GSK3 Proteins 0.000 description 1
IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
102100034004 Gamma-adducin Human genes 0.000 description 1
208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
206010072075 Gerstmann-Straussler-Scheinker syndrome Diseases 0.000 description 1
244000194101 Ginkgo biloba Species 0.000 description 1
102100039289 Glial fibrillary acidic protein Human genes 0.000 description 1
101710193519 Glial fibrillary acidic protein Proteins 0.000 description 1
102000006395 Globulins Human genes 0.000 description 1
108010044091 Globulins Proteins 0.000 description 1
102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
244000068988 Glycine max Species 0.000 description 1
235000010469 Glycine max Nutrition 0.000 description 1
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
229930186217 Glycolipid Natural products 0.000 description 1
241000282575 Gorilla Species 0.000 description 1
241000606768 Haemophilus influenzae Species 0.000 description 1
102000014702 Haptoglobin Human genes 0.000 description 1
108050005077 Haptoglobin Proteins 0.000 description 1
206010019196 Head injury Diseases 0.000 description 1
241000590002 Helicobacter pylori Species 0.000 description 1
206010019889 Hereditary neuropathic amyloidosis Diseases 0.000 description 1
208000017604 Hodgkin disease Diseases 0.000 description 1
208000021519 Hodgkin lymphoma Diseases 0.000 description 1
208000010747 Hodgkins lymphoma Diseases 0.000 description 1
241001272567 Hominoidea Species 0.000 description 1
101000799011 Homo sapiens Gamma-adducin Proteins 0.000 description 1
101000934372 Homo sapiens Macrosialin Proteins 0.000 description 1
101000772194 Homo sapiens Transthyretin Proteins 0.000 description 1
108010001336 Horseradish Peroxidase Proteins 0.000 description 1
241000701024 Human betaherpesvirus 5 Species 0.000 description 1
241000725303 Human immunodeficiency virus Species 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
201000000194 ITM2B-related cerebral amyloid angiopathy 2 Diseases 0.000 description 1
WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
208000003456 Juvenile Arthritis Diseases 0.000 description 1
206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 1
208000007976 Ketosis Diseases 0.000 description 1
SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 1
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
108090001090 Lectins Proteins 0.000 description 1
102000004856 Lectins Human genes 0.000 description 1
241000222724 Leishmania amazonensis Species 0.000 description 1
206010024229 Leprosy Diseases 0.000 description 1
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
208000009829 Lewy Body Disease Diseases 0.000 description 1
108090001030 Lipoproteins Proteins 0.000 description 1
102000004895 Lipoproteins Human genes 0.000 description 1
241000186779 Listeria monocytogenes Species 0.000 description 1
108060001084 Luciferase Proteins 0.000 description 1
239000005089 Luciferase Substances 0.000 description 1
LUWJPTVQOMUZLW-UHFFFAOYSA-N Luxol fast blue MBS Chemical compound [Cu++].Cc1ccccc1N\C(N)=N\c1ccccc1C.Cc1ccccc1N\C(N)=N\c1ccccc1C.OS(=O)(=O)c1cccc2c3nc(nc4nc([n-]c5[n-]c(nc6nc(n3)c3ccccc63)c3c(cccc53)S(O)(=O)=O)c3ccccc43)c12 LUWJPTVQOMUZLW-UHFFFAOYSA-N 0.000 description 1
102100025136 Macrosialin Human genes 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
235000019759 Maize starch Nutrition 0.000 description 1
GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
240000004658 Medicago sativa Species 0.000 description 1
235000017587 Medicago sativa ssp. sativa Nutrition 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
206010060880 Monoclonal gammopathy Diseases 0.000 description 1
201000002795 Muckle-Wells syndrome Diseases 0.000 description 1
241000187479 Mycobacterium tuberculosis Species 0.000 description 1
241000202934 Mycoplasma pneumoniae Species 0.000 description 1
206010068871 Myotonic dystrophy Diseases 0.000 description 1
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 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
241000588653 Neisseria Species 0.000 description 1
208000010577 Niemann-Pick disease type C Diseases 0.000 description 1
206010031252 Osteomyelitis Diseases 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
241000282577 Pan troglodytes Species 0.000 description 1
229930040373 Paraformaldehyde Natural products 0.000 description 1
208000027089 Parkinsonian disease Diseases 0.000 description 1
206010034010 Parkinsonism Diseases 0.000 description 1
108010046016 Peanut Agglutinin Proteins 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
241001494479 Pecora Species 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
208000037581 Persistent Infection Diseases 0.000 description 1
206010034719 Personality change Diseases 0.000 description 1
208000024571 Pick disease Diseases 0.000 description 1
235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
241000018646 Pinus brutia Species 0.000 description 1
235000011613 Pinus brutia Nutrition 0.000 description 1
240000004713 Pisum sativum Species 0.000 description 1
235000010582 Pisum sativum Nutrition 0.000 description 1
241000223960 Plasmodium falciparum Species 0.000 description 1
229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
229920002319 Poly(methyl acrylate) Polymers 0.000 description 1
229920000954 Polyglycolide Polymers 0.000 description 1
206010036105 Polyneuropathy Diseases 0.000 description 1
208000036757 Postencephalitic parkinsonism Diseases 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
208000023146 Pre-existing disease Diseases 0.000 description 1
206010036673 Primary amyloidosis Diseases 0.000 description 1
208000014675 Prion-associated disease Diseases 0.000 description 1
108010048233 Procalcitonin Proteins 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
239000004365 Protease Substances 0.000 description 1
241000589517 Pseudomonas aeruginosa Species 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
208000033464 Reiter syndrome Diseases 0.000 description 1
206010038389 Renal cancer Diseases 0.000 description 1
208000006265 Renal cell carcinoma Diseases 0.000 description 1
241000283984 Rodentia Species 0.000 description 1
108700028909 Serum Amyloid A Proteins 0.000 description 1
101710190759 Serum amyloid A protein Proteins 0.000 description 1
208000009106 Shy-Drager Syndrome Diseases 0.000 description 1
241000700584 Simplexvirus Species 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
229920002125 Sokalan® Polymers 0.000 description 1
241000191967 Staphylococcus aureus Species 0.000 description 1
108010090804 Streptavidin Proteins 0.000 description 1
241000194019 Streptococcus mutans Species 0.000 description 1
241000194021 Streptococcus suis Species 0.000 description 1
208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
241000701093 Suid alphaherpesvirus 1 Species 0.000 description 1
241000282887 Suidae Species 0.000 description 1
102000019197 Superoxide Dismutase Human genes 0.000 description 1
108010012715 Superoxide dismutase Proteins 0.000 description 1
210000001744 T-lymphocyte Anatomy 0.000 description 1
208000034799 Tauopathies Diseases 0.000 description 1
206010043376 Tetanus Diseases 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
102000004338 Transferrin Human genes 0.000 description 1
108090000901 Transferrin Proteins 0.000 description 1
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
102000004243 Tubulin Human genes 0.000 description 1
108090000704 Tubulin Proteins 0.000 description 1
208000007930 Type C Niemann-Pick Disease Diseases 0.000 description 1
208000024780 Urticaria Diseases 0.000 description 1
201000004810 Vascular dementia Diseases 0.000 description 1
241000700605 Viruses Species 0.000 description 1
229930003427 Vitamin E Natural products 0.000 description 1
208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
108010046516 Wheat Germ Agglutinins Proteins 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
229940022698 acetylcholinesterase Drugs 0.000 description 1
230000009056 active transport Effects 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
239000000853 adhesive Substances 0.000 description 1
230000001070 adhesive effect Effects 0.000 description 1
230000002411 adverse Effects 0.000 description 1
239000008272 agar Substances 0.000 description 1
229940023476 agar Drugs 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
150000001320 aldopentoses Chemical class 0.000 description 1
229940072056 alginate Drugs 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
125000005055 alkyl alkoxy group Chemical group 0.000 description 1
125000002877 alkyl aryl group Chemical group 0.000 description 1
125000000304 alkynyl group Chemical group 0.000 description 1
208000026935 allergic disease Diseases 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
230000006933 amyloid-beta aggregation Effects 0.000 description 1
238000010171 animal model Methods 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
230000001430 anti-depressive effect Effects 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
230000000561 anti-psychotic effect Effects 0.000 description 1
230000001475 anti-trypsic effect Effects 0.000 description 1
230000005875 antibody response Effects 0.000 description 1
239000000935 antidepressant agent Substances 0.000 description 1
229940005513 antidepressants Drugs 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
239000000164 antipsychotic agent Substances 0.000 description 1
229940005529 antipsychotics Drugs 0.000 description 1
201000007201 aphasia Diseases 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
125000001204 arachidyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000003140 astrocytic effect Effects 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
125000003828 azulenyl group Chemical group 0.000 description 1
210000003719 b-lymphocyte Anatomy 0.000 description 1
235000004251 balanced diet Nutrition 0.000 description 1
235000013871 bee wax Nutrition 0.000 description 1
239000012166 beeswax Substances 0.000 description 1
239000000440 bentonite Substances 0.000 description 1
229910000278 bentonite Inorganic materials 0.000 description 1
229940092782 bentonite Drugs 0.000 description 1
235000012216 bentonite Nutrition 0.000 description 1
SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
239000002439 beta secretase inhibitor Substances 0.000 description 1
MSWZFWKMSRAUBD-QZABAPFNSA-N beta-D-glucosamine Chemical compound N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-QZABAPFNSA-N 0.000 description 1
108010005774 beta-Galactosidase Proteins 0.000 description 1
GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
235000013361 beverage Nutrition 0.000 description 1
230000008512 biological response Effects 0.000 description 1
230000005540 biological transmission Effects 0.000 description 1
125000004057 biotinyl group Chemical group [H]N1C(=O)N([H])[C@]2([H])[C@@]([H])(SC([H])([H])[C@]12[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
239000005388 borosilicate glass Substances 0.000 description 1
208000005881 bovine spongiform encephalopathy Diseases 0.000 description 1
210000005013 brain tissue Anatomy 0.000 description 1
239000000872 buffer Substances 0.000 description 1
239000007853 buffer solution Substances 0.000 description 1
239000007975 buffered saline Substances 0.000 description 1
239000004067 bulking agent Substances 0.000 description 1
125000005510 but-1-en-2-yl group Chemical group 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
235000011132 calcium sulphate Nutrition 0.000 description 1
235000013736 caramel Nutrition 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
125000000837 carbohydrate group Chemical group 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
229960004424 carbon dioxide Drugs 0.000 description 1
125000001721 carboxyacetyl group Chemical group 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
235000012730 carminic acid Nutrition 0.000 description 1
208000003295 carpal tunnel syndrome Diseases 0.000 description 1
229940047495 celebrex Drugs 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
238000004113 cell culture Methods 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
235000013339 cereals Nutrition 0.000 description 1
210000003710 cerebral cortex Anatomy 0.000 description 1
229930183167 cerebroside Natural products 0.000 description 1
RIZIAUKTHDLMQX-UHFFFAOYSA-N cerebroside D Natural products CCCCCCCCCCCCCCCCC(O)C(=O)NC(C(O)C=CCCC=C(C)CCCCCCCCC)COC1OC(CO)C(O)C(O)C1O RIZIAUKTHDLMQX-UHFFFAOYSA-N 0.000 description 1
210000001175 cerebrospinal fluid Anatomy 0.000 description 1
208000026106 cerebrovascular disease Diseases 0.000 description 1
WUTYZMFRCNBCHQ-PSASIEDQSA-N cevimeline Chemical compound C1S[C@H](C)O[C@]21C(CC1)CCN1C2 WUTYZMFRCNBCHQ-PSASIEDQSA-N 0.000 description 1
229960001314 cevimeline Drugs 0.000 description 1
238000006243 chemical reaction Methods 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000013626 chemical specie Substances 0.000 description 1
229940038705 chlamydia trachomatis Drugs 0.000 description 1
239000000544 cholinesterase inhibitor Substances 0.000 description 1
WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
229960004170 clozapine Drugs 0.000 description 1
QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 1
239000003240 coconut oil Substances 0.000 description 1
235000019864 coconut oil Nutrition 0.000 description 1
230000001149 cognitive effect Effects 0.000 description 1
238000004737 colorimetric analysis Methods 0.000 description 1
208000004209 confusion Diseases 0.000 description 1
239000000039 congener Substances 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
238000011443 conventional therapy Methods 0.000 description 1
229920001577 copolymer Polymers 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
230000000875 corresponding effect Effects 0.000 description 1
230000001054 cortical effect Effects 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
229960003624 creatine Drugs 0.000 description 1
239000006046 creatine Substances 0.000 description 1
238000004132 cross linking Methods 0.000 description 1
230000009260 cross reactivity Effects 0.000 description 1
208000022993 cryopyrin-associated periodic syndrome Diseases 0.000 description 1
WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
125000006165 cyclic alkyl group Chemical group 0.000 description 1
125000006547 cyclononyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
231100000895 deafness Toxicity 0.000 description 1
230000007850 degeneration Effects 0.000 description 1
230000003412 degenerative effect Effects 0.000 description 1
238000012217 deletion Methods 0.000 description 1
230000037430 deletion Effects 0.000 description 1
238000000326 densiometry Methods 0.000 description 1
150000008266 deoxy sugars Chemical class 0.000 description 1
239000007933 dermal patch Substances 0.000 description 1
238000013461 design Methods 0.000 description 1
238000001514 detection method Methods 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
235000019700 dicalcium phosphate Nutrition 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
229940042935 dichlorodifluoromethane Drugs 0.000 description 1
229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
230000005750 disease progression Effects 0.000 description 1
208000037765 diseases and disorders Diseases 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
239000008157 edible vegetable oil Substances 0.000 description 1
230000002526 effect on cardiovascular system Effects 0.000 description 1
238000005538 encapsulation Methods 0.000 description 1
201000011523 endocrine gland cancer Diseases 0.000 description 1
230000000688 enterotoxigenic effect Effects 0.000 description 1
229940011871 estrogen Drugs 0.000 description 1
239000000262 estrogen Substances 0.000 description 1
BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
235000019325 ethyl cellulose Nutrition 0.000 description 1
229920001249 ethyl cellulose Polymers 0.000 description 1
DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
230000003203 everyday effect Effects 0.000 description 1
229940062770 evoxac Drugs 0.000 description 1
230000010326 executive functioning Effects 0.000 description 1
239000003925 fat Substances 0.000 description 1
235000013861 fat-free Nutrition 0.000 description 1
235000019197 fats Nutrition 0.000 description 1
229940012952 fibrinogen Drugs 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 description 1
235000013305 food Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
239000003540 gamma secretase inhibitor Substances 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
238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
239000000499 gel Substances 0.000 description 1
238000011773 genetically engineered mouse model Methods 0.000 description 1
210000005046 glial fibrillary acidic protein Anatomy 0.000 description 1
235000001727 glucose Nutrition 0.000 description 1
MNQZXJOMYWMBOU-UHFFFAOYSA-N glyceraldehyde Chemical compound OCC(O)C=O MNQZXJOMYWMBOU-UHFFFAOYSA-N 0.000 description 1
108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
229930182470 glycoside Natural products 0.000 description 1
230000013595 glycosylation Effects 0.000 description 1
238000006206 glycosylation reaction Methods 0.000 description 1
239000003979 granulating agent Substances 0.000 description 1
208000035474 group of disease Diseases 0.000 description 1
229940047650 haemophilus influenzae Drugs 0.000 description 1
125000004994 halo alkoxy alkyl group Chemical group 0.000 description 1
125000001188 haloalkyl group Chemical group 0.000 description 1
229960003878 haloperidol Drugs 0.000 description 1
230000036541 health Effects 0.000 description 1
208000016354 hearing loss disease Diseases 0.000 description 1
230000004217 heart function Effects 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
229940037467 helicobacter pylori Drugs 0.000 description 1
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
125000002768 hydroxyalkyl group Chemical group 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
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 1
150000002454 idoses Chemical class 0.000 description 1
238000010191 image analysis Methods 0.000 description 1
MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
238000003018 immunoassay Methods 0.000 description 1
238000011532 immunohistochemical staining Methods 0.000 description 1
230000001024 immunotherapeutic effect Effects 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000000099 in vitro assay Methods 0.000 description 1
239000005414 inactive ingredient Substances 0.000 description 1
201000008319 inclusion body myositis Diseases 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
238000001802 infusion Methods 0.000 description 1
229940102223 injectable solution Drugs 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
206010022498 insulinoma Diseases 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
230000009545 invasion Effects 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
230000007794 irritation Effects 0.000 description 1
210000004153 islets of langerhan Anatomy 0.000 description 1
229960002725 isoflurane Drugs 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
150000002584 ketoses Chemical class 0.000 description 1
208000017169 kidney disease Diseases 0.000 description 1
206010023497 kuru Diseases 0.000 description 1
150000003951 lactams Chemical group 0.000 description 1
229910052747 lanthanoid Inorganic materials 0.000 description 1
150000002602 lanthanoids Chemical class 0.000 description 1
201000010901 lateral sclerosis Diseases 0.000 description 1
239000002523 lectin Substances 0.000 description 1
231100000518 lethal Toxicity 0.000 description 1
230000001665 lethal effect Effects 0.000 description 1
210000004558 lewy body Anatomy 0.000 description 1
239000002502 liposome Substances 0.000 description 1
239000006193 liquid solution Substances 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
239000008176 lyophilized powder Substances 0.000 description 1
201000000564 macroglobulinemia Diseases 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 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
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
230000036210 malignancy Effects 0.000 description 1
125000002960 margaryl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000003550 marker Substances 0.000 description 1
238000002483 medication Methods 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
239000012528 membrane Substances 0.000 description 1
206010027175 memory impairment Diseases 0.000 description 1
230000003340 mental effect Effects 0.000 description 1
230000003924 mental process Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
229960002900 methylcellulose Drugs 0.000 description 1
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
230000000813 microbial effect Effects 0.000 description 1
239000003094 microcapsule Substances 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
210000000274 microglia Anatomy 0.000 description 1
238000001000 micrograph Methods 0.000 description 1
239000011859 microparticle Substances 0.000 description 1
235000013336 milk Nutrition 0.000 description 1
239000008267 milk Substances 0.000 description 1
210000004080 milk Anatomy 0.000 description 1
230000003278 mimic effect Effects 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000000877 morphologic effect Effects 0.000 description 1
230000007659 motor function Effects 0.000 description 1
239000000472 muscarinic agonist Substances 0.000 description 1
201000000050 myeloid neoplasm Diseases 0.000 description 1
XERMVRJWJCKFMG-SFHVURJKSA-N n-[(2s)-1-[4-(3-aminopropylamino)butylamino]-3-hydroxy-1-oxopropan-2-yl]-4-[4-(diaminomethylideneamino)phenyl]butanamide Chemical compound NCCCNCCCCNC(=O)[C@H](CO)NC(=O)CCCC1=CC=C(N=C(N)N)C=C1 XERMVRJWJCKFMG-SFHVURJKSA-N 0.000 description 1
NFVJNJQRWPQVOA-UHFFFAOYSA-N n-[2-chloro-5-(trifluoromethyl)phenyl]-2-[3-(4-ethyl-5-ethylsulfanyl-1,2,4-triazol-3-yl)piperidin-1-yl]acetamide Chemical compound CCN1C(SCC)=NN=C1C1CN(CC(=O)NC=2C(=CC=C(C=2)C(F)(F)F)Cl)CCC1 NFVJNJQRWPQVOA-UHFFFAOYSA-N 0.000 description 1
125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
229920001206 natural gum Polymers 0.000 description 1
230000001722 neurochemical effect Effects 0.000 description 1
210000002682 neurofibrillary tangle Anatomy 0.000 description 1
210000005044 neurofilament Anatomy 0.000 description 1
125000001196 nonadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
231100000956 nontoxicity Toxicity 0.000 description 1
125000003729 nucleotide group Chemical group 0.000 description 1
239000003921 oil Substances 0.000 description 1
239000012053 oil suspension Substances 0.000 description 1
235000019198 oils Nutrition 0.000 description 1
229960005017 olanzapine Drugs 0.000 description 1
KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
230000004203 pancreatic function Effects 0.000 description 1
208000021255 pancreatic insulinoma Diseases 0.000 description 1
208000002593 pantothenate kinase-associated neurodegeneration Diseases 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
229920002866 paraformaldehyde Polymers 0.000 description 1
230000009057 passive transport Effects 0.000 description 1
244000052769 pathogen Species 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000008188 pellet Substances 0.000 description 1
125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000002972 pentoses Chemical class 0.000 description 1
230000010412 perfusion Effects 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
230000003285 pharmacodynamic effect Effects 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000001828 phenalenyl group Chemical group C1(C=CC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
229950000688 phenothiazine Drugs 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003905 phosphatidylinositols Chemical class 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
230000037081 physical activity Effects 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
230000035479 physiological effects, processes and functions Effects 0.000 description 1
235000002949 phytic acid Nutrition 0.000 description 1
229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
108010054442 polyalanine Proteins 0.000 description 1
108010040003 polyglutamine Proteins 0.000 description 1
229920000155 polyglutamine Polymers 0.000 description 1
230000007824 polyneuropathy Effects 0.000 description 1
229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
229920006324 polyoxymethylene Polymers 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
239000013641 positive control Substances 0.000 description 1
238000010149 post-hoc-test Methods 0.000 description 1
208000000170 postencephalitic Parkinson disease Diseases 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
244000144977 poultry Species 0.000 description 1
239000002243 precursor Substances 0.000 description 1
CWCXERYKLSEGEZ-KDKHKZEGSA-N procalcitonin Chemical compound C([C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(O)=O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@H]1NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@@H](N)CSSC1)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 CWCXERYKLSEGEZ-KDKHKZEGSA-N 0.000 description 1
239000000047 product Substances 0.000 description 1
201000002212 progressive supranuclear palsy Diseases 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
230000006916 protein interaction Effects 0.000 description 1
230000020978 protein processing Effects 0.000 description 1
230000004850 protein–protein interaction Effects 0.000 description 1
238000013138 pruning Methods 0.000 description 1
CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
208000002574 reactive arthritis Diseases 0.000 description 1
238000011084 recovery Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
201000010174 renal carcinoma Diseases 0.000 description 1
230000000979 retarding effect Effects 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
239000011435 rock Substances 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
230000009156 sensorimotor behavior Effects 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
239000000377 silicon dioxide Substances 0.000 description 1
238000009097 single-agent therapy Methods 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
229940079832 sodium starch glycolate Drugs 0.000 description 1
229920003109 sodium starch glycolate Polymers 0.000 description 1
239000008109 sodium starch glycolate Substances 0.000 description 1
239000012453 solvate Substances 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
125000006850 spacer group Chemical group 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
210000000130 stem cell Anatomy 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
239000003206 sterilizing agent Substances 0.000 description 1
230000003637 steroidlike Effects 0.000 description 1
208000003755 striatonigral degeneration Diseases 0.000 description 1
230000002739 subcortical effect Effects 0.000 description 1
125000004426 substituted alkynyl group Chemical group 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
230000000153 supplemental effect Effects 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
230000003956 synaptic plasticity Effects 0.000 description 1
230000009782 synaptic response Effects 0.000 description 1
230000009897 systematic effect Effects 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
230000004797 therapeutic response Effects 0.000 description 1
125000004001 thioalkyl group Chemical group 0.000 description 1
125000005296 thioaryloxy group Chemical group 0.000 description 1
125000005404 thioheteroaryloxy group Chemical group 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000000699 topical effect Effects 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
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
230000037317 transdermal delivery Effects 0.000 description 1
239000012581 transferrin Substances 0.000 description 1
201000007905 transthyretin amyloidosis Diseases 0.000 description 1
150000003626 triacylglycerols Chemical class 0.000 description 1
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
229940029284 trichlorofluoromethane Drugs 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
239000002753 trypsin inhibitor Substances 0.000 description 1
201000008827 tuberculosis Diseases 0.000 description 1
125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
229920002554 vinyl polymer Polymers 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
239000001993 wax Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
229920001285 xanthan gum Polymers 0.000 description 1
239000000230 xanthan gum Substances 0.000 description 1
235000010493 xanthan gum Nutrition 0.000 description 1
229940082509 xanthan gum Drugs 0.000 description 1