JP2010509205A - Ｐｏｓｈ及びｐｏｓｈ−ａｐ阻害剤としてのピリミジン誘導体 - Google Patents
Ｐｏｓｈ及びｐｏｓｈ−ａｐ阻害剤としてのピリミジン誘導体 Download PDFInfo
- Publication number
- JP2010509205A JP2010509205A JP2009535189A JP2009535189A JP2010509205A JP 2010509205 A JP2010509205 A JP 2010509205A JP 2009535189 A JP2009535189 A JP 2009535189A JP 2009535189 A JP2009535189 A JP 2009535189A JP 2010509205 A JP2010509205 A JP 2010509205A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- posh
- polypeptide
- disease
- heterocyclyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003112 inhibitor Substances 0.000 title abstract description 31
- 150000003230 pyrimidines Chemical class 0.000 title abstract description 11
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title abstract description 6
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 194
- 229920001184 polypeptide Polymers 0.000 claims abstract description 193
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 193
- 230000000694 effects Effects 0.000 claims abstract description 116
- 238000010798 ubiquitination Methods 0.000 claims abstract description 42
- 208000036142 Viral infection Diseases 0.000 claims abstract description 41
- 230000009385 viral infection Effects 0.000 claims abstract description 41
- 230000034512 ubiquitination Effects 0.000 claims abstract description 40
- 208000012902 Nervous system disease Diseases 0.000 claims abstract description 36
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 claims abstract description 36
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 claims abstract description 36
- 208000025966 Neurological disease Diseases 0.000 claims abstract description 22
- 101000837060 Homo sapiens E3 ubiquitin-protein ligase SH3RF1 Proteins 0.000 claims abstract description 15
- 108090000623 proteins and genes Proteins 0.000 claims description 178
- 102000004169 proteins and genes Human genes 0.000 claims description 158
- 150000001875 compounds Chemical class 0.000 claims description 152
- 210000004027 cell Anatomy 0.000 claims description 92
- 238000000034 method Methods 0.000 claims description 87
- 239000003795 chemical substances by application Substances 0.000 claims description 68
- 101001035137 Homo sapiens Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein Proteins 0.000 claims description 59
- 102100039923 Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein Human genes 0.000 claims description 59
- 241000700605 Viruses Species 0.000 claims description 58
- 125000000623 heterocyclic group Chemical group 0.000 claims description 49
- 125000000217 alkyl group Chemical group 0.000 claims description 48
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 45
- 125000003118 aryl group Chemical group 0.000 claims description 34
- 208000031886 HIV Infections Diseases 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 32
- -1 1,3,4-triazinyl Chemical group 0.000 claims description 28
- 125000001072 heteroaryl group Chemical group 0.000 claims description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims description 27
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 27
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 25
- 201000010099 disease Diseases 0.000 claims description 24
- 208000024827 Alzheimer disease Diseases 0.000 claims description 23
- 229940125904 compound 1 Drugs 0.000 claims description 23
- 238000004519 manufacturing process Methods 0.000 claims description 23
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 22
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 claims description 21
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 claims description 21
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 claims description 21
- 241000713772 Human immunodeficiency virus 1 Species 0.000 claims description 21
- 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 claims description 21
- 208000035475 disorder Diseases 0.000 claims description 21
- 229910052717 sulfur Inorganic materials 0.000 claims description 21
- 241000713340 Human immunodeficiency virus 2 Species 0.000 claims description 20
- 230000002401 inhibitory effect Effects 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 19
- 125000005842 heteroatom Chemical group 0.000 claims description 19
- 229940125782 compound 2 Drugs 0.000 claims description 13
- 229940125898 compound 5 Drugs 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 108050008861 SH3 domains Proteins 0.000 claims description 12
- 102000000395 SH3 domains Human genes 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 241001493065 dsRNA viruses Species 0.000 claims description 12
- 241001492409 Retro-transcribing viruses Species 0.000 claims description 11
- 230000000840 anti-viral effect Effects 0.000 claims description 11
- 102000052665 human SH3RF1 Human genes 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 230000008569 process Effects 0.000 claims description 11
- 241000711549 Hepacivirus C Species 0.000 claims description 10
- 230000000926 neurological effect Effects 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 150000003384 small molecules Chemical class 0.000 claims description 10
- 239000004593 Epoxy Substances 0.000 claims description 9
- 229920006395 saturated elastomer Polymers 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 201000000980 schizophrenia Diseases 0.000 claims description 8
- 241000700721 Hepatitis B virus Species 0.000 claims description 7
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 7
- 230000005764 inhibitory process Effects 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 7
- 241001115402 Ebolavirus Species 0.000 claims description 6
- 208000023105 Huntington disease Diseases 0.000 claims description 6
- 241000713666 Lentivirus Species 0.000 claims description 6
- 208000018737 Parkinson disease Diseases 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 5
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- 241000713711 Primate lentivirus group Species 0.000 claims description 4
- 208000000389 T-cell leukemia Diseases 0.000 claims description 4
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000002619 bicyclic group Chemical group 0.000 claims description 4
- 125000001188 haloalkyl group Chemical group 0.000 claims description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 229940126214 compound 3 Drugs 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 125000004529 1,2,3-triazinyl group Chemical group N1=NN=C(C=C1)* 0.000 claims description 2
- 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 claims description 2
- 208000020401 Depressive disease Diseases 0.000 claims description 2
- 125000002015 acyclic group Chemical group 0.000 claims description 2
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000003310 benzodiazepinyl group Chemical group N1N=C(C=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims 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 claims description 2
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims description 2
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 claims description 2
- 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000005946 imidazo[1,2-a]pyridyl group Chemical group 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000000169 tricyclic heterocycle group Chemical group 0.000 claims description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- 235000010290 biphenyl Nutrition 0.000 claims 1
- 239000004305 biphenyl Substances 0.000 claims 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 102100028660 E3 ubiquitin-protein ligase SH3RF1 Human genes 0.000 abstract description 2
- 235000018102 proteins Nutrition 0.000 description 149
- 238000003556 assay Methods 0.000 description 72
- 108090000848 Ubiquitin Proteins 0.000 description 64
- 102000044159 Ubiquitin Human genes 0.000 description 64
- 239000000203 mixture Substances 0.000 description 49
- 230000015572 biosynthetic process Effects 0.000 description 28
- 238000012360 testing method Methods 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 23
- 230000006870 function Effects 0.000 description 22
- 230000001404 mediated effect Effects 0.000 description 22
- 239000000243 solution Substances 0.000 description 22
- 230000003993 interaction Effects 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 19
- 239000000543 intermediate Substances 0.000 description 19
- 102000004190 Enzymes Human genes 0.000 description 18
- 108090000790 Enzymes Proteins 0.000 description 18
- 238000001514 detection method Methods 0.000 description 18
- 239000000758 substrate Substances 0.000 description 17
- 238000003786 synthesis reaction Methods 0.000 description 17
- 239000002253 acid Substances 0.000 description 16
- 238000011534 incubation Methods 0.000 description 16
- 239000002245 particle Substances 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 14
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 14
- 230000027455 binding Effects 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 13
- 230000003612 virological effect Effects 0.000 description 13
- 230000009918 complex formation Effects 0.000 description 11
- 230000010305 self ubiquitination Effects 0.000 description 11
- 230000014509 gene expression Effects 0.000 description 10
- 230000037361 pathway Effects 0.000 description 10
- 238000012545 processing Methods 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 108010036933 Presenilin-1 Proteins 0.000 description 9
- 102000012412 Presenilin-1 Human genes 0.000 description 9
- 108091030071 RNAI Proteins 0.000 description 9
- 239000003443 antiviral agent Substances 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 230000009368 gene silencing by RNA Effects 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 230000006907 apoptotic process Effects 0.000 description 8
- 239000011324 bead Substances 0.000 description 8
- 235000019441 ethanol Nutrition 0.000 description 8
- 108091006047 fluorescent proteins Proteins 0.000 description 8
- 102000034287 fluorescent proteins Human genes 0.000 description 8
- 108020001507 fusion proteins Proteins 0.000 description 8
- 102000037865 fusion proteins Human genes 0.000 description 8
- 238000013537 high throughput screening Methods 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 238000007423 screening assay Methods 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000001890 transfection Methods 0.000 description 8
- 230000029302 virus maturation Effects 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 description 7
- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 7
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 7
- 108010057466 NF-kappa B Proteins 0.000 description 7
- 102000003945 NF-kappa B Human genes 0.000 description 7
- 108010067390 Viral Proteins Proteins 0.000 description 7
- 229960000583 acetic acid Drugs 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 230000031018 biological processes and functions Effects 0.000 description 7
- 230000007423 decrease Effects 0.000 description 7
- 239000000499 gel Substances 0.000 description 7
- 239000012362 glacial acetic acid Substances 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 238000013518 transcription Methods 0.000 description 7
- 230000035897 transcription Effects 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 230000004807 localization Effects 0.000 description 6
- 230000035800 maturation Effects 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 229940124597 therapeutic agent Drugs 0.000 description 6
- 241001430294 unidentified retrovirus Species 0.000 description 6
- 230000017613 viral reproduction Effects 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 108700024394 Exon Proteins 0.000 description 5
- 102000013446 GTP Phosphohydrolases Human genes 0.000 description 5
- 108091006109 GTPases Proteins 0.000 description 5
- 102000012419 Presenilin-2 Human genes 0.000 description 5
- 108010036908 Presenilin-2 Proteins 0.000 description 5
- 102000015499 Presenilins Human genes 0.000 description 5
- 108010050254 Presenilins Proteins 0.000 description 5
- 108020004459 Small interfering RNA Proteins 0.000 description 5
- 101800001117 Ubiquitin-related Proteins 0.000 description 5
- 108010004469 allophycocyanin Proteins 0.000 description 5
- 150000001413 amino acids Chemical group 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 231100000433 cytotoxic Toxicity 0.000 description 5
- 230000001472 cytotoxic effect Effects 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 238000010172 mouse model Methods 0.000 description 5
- 150000007523 nucleic acids Chemical class 0.000 description 5
- 102000039446 nucleic acids Human genes 0.000 description 5
- 108020004707 nucleic acids Proteins 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000000159 protein binding assay Methods 0.000 description 5
- 102000016914 ras Proteins Human genes 0.000 description 5
- 108010014186 ras Proteins Proteins 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 230000003248 secreting effect Effects 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 5
- 230000014616 translation Effects 0.000 description 5
- 230000032258 transport Effects 0.000 description 5
- 108091005957 yellow fluorescent proteins Proteins 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 4
- 102000011068 Cdc42 Human genes 0.000 description 4
- 108050001278 Cdc42 Proteins 0.000 description 4
- 102000005853 Clathrin Human genes 0.000 description 4
- 108010019874 Clathrin Proteins 0.000 description 4
- 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 4
- 241000711950 Filoviridae Species 0.000 description 4
- 102100034347 Integrase Human genes 0.000 description 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 230000034303 cell budding Effects 0.000 description 4
- 239000006143 cell culture medium Substances 0.000 description 4
- 230000033077 cellular process Effects 0.000 description 4
- 229930193282 clathrin Natural products 0.000 description 4
- 230000021615 conjugation Effects 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 108010082025 cyan fluorescent protein Proteins 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000001378 electrochemiluminescence detection Methods 0.000 description 4
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 4
- 238000000695 excitation spectrum Methods 0.000 description 4
- 239000007850 fluorescent dye Substances 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 238000003197 gene knockdown Methods 0.000 description 4
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 239000012139 lysis buffer Substances 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 208000015122 neurodegenerative disease Diseases 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 230000004850 protein–protein interaction Effects 0.000 description 4
- 230000017854 proteolysis Effects 0.000 description 4
- 230000011664 signaling Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 4
- 210000003412 trans-golgi network Anatomy 0.000 description 4
- 238000003158 yeast two-hybrid assay Methods 0.000 description 4
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 108700028369 Alleles Proteins 0.000 description 3
- 101100181041 Arabidopsis thaliana KINUA gene Proteins 0.000 description 3
- 101150072950 BRCA1 gene Proteins 0.000 description 3
- 101150059668 Bard1 gene Proteins 0.000 description 3
- 101800001318 Capsid protein VP4 Proteins 0.000 description 3
- 101710163595 Chaperone protein DnaK Proteins 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 101100484539 Drosophila melanogaster Vav gene Proteins 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 102100035273 E3 ubiquitin-protein ligase CBL-B Human genes 0.000 description 3
- 102100027259 Ena/VASP-like protein Human genes 0.000 description 3
- 102100040351 FK506-binding protein 15 Human genes 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 101710178376 Heat shock 70 kDa protein Proteins 0.000 description 3
- 101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 description 3
- 101710113864 Heat shock protein 90 Proteins 0.000 description 3
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 description 3
- 101000737265 Homo sapiens E3 ubiquitin-protein ligase CBL-B Proteins 0.000 description 3
- 101001057143 Homo sapiens Ena/VASP-like protein Proteins 0.000 description 3
- 101000891018 Homo sapiens FK506-binding protein 15 Proteins 0.000 description 3
- 101000987310 Homo sapiens Serine/threonine-protein kinase PAK 2 Proteins 0.000 description 3
- 101000617738 Homo sapiens Survival motor neuron protein Proteins 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- LFZAGIJXANFPFN-UHFFFAOYSA-N N-[3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-thiophen-2-ylpropyl]acetamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CCC(C=1SC=CC=1)NC(C)=O)C LFZAGIJXANFPFN-UHFFFAOYSA-N 0.000 description 3
- 101150097297 Nedd4 gene Proteins 0.000 description 3
- 102100023031 Neural Wiskott-Aldrich syndrome protein Human genes 0.000 description 3
- 108010009519 Neuronal Wiskott-Aldrich Syndrome Protein Proteins 0.000 description 3
- 101700056750 PAK1 Proteins 0.000 description 3
- 102000038030 PI3Ks Human genes 0.000 description 3
- 108091007960 PI3Ks Proteins 0.000 description 3
- 101150058540 RAC1 gene Proteins 0.000 description 3
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 3
- 102100022122 Ras-related C3 botulinum toxin substrate 1 Human genes 0.000 description 3
- 108700008625 Reporter Genes Proteins 0.000 description 3
- 102100027609 Rho-related GTP-binding protein RhoD Human genes 0.000 description 3
- 102100027910 Serine/threonine-protein kinase PAK 1 Human genes 0.000 description 3
- 102100027939 Serine/threonine-protein kinase PAK 2 Human genes 0.000 description 3
- 241000713311 Simian immunodeficiency virus Species 0.000 description 3
- 102100027650 Sprouty-related, EVH1 domain-containing protein 2 Human genes 0.000 description 3
- 101710112211 Sprouty-related, EVH1 domain-containing protein 2 Proteins 0.000 description 3
- 102100021947 Survival motor neuron protein Human genes 0.000 description 3
- 108700030796 Tsg101 Proteins 0.000 description 3
- 101150072717 Tsg101 gene Proteins 0.000 description 3
- 102000018478 Ubiquitin-Activating Enzymes Human genes 0.000 description 3
- 108010091546 Ubiquitin-Activating Enzymes Proteins 0.000 description 3
- 108060008747 Ubiquitin-Conjugating Enzyme Proteins 0.000 description 3
- 102000003431 Ubiquitin-Conjugating Enzyme Human genes 0.000 description 3
- 101150042678 VAV1 gene Proteins 0.000 description 3
- 102100021164 Vasodilator-stimulated phosphoprotein Human genes 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 238000007413 biotinylation Methods 0.000 description 3
- 230000006287 biotinylation Effects 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 239000013592 cell lysate Substances 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 210000002806 clathrin-coated vesicle Anatomy 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 238000001739 density measurement Methods 0.000 description 3
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 3
- 229960003964 deoxycholic acid Drugs 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 238000000295 emission spectrum Methods 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 230000005284 excitation Effects 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 3
- 108010027225 gag-pol Fusion Proteins Proteins 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 238000003119 immunoblot Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000002452 interceptive effect Effects 0.000 description 3
- 230000010189 intracellular transport Effects 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 102000006240 membrane receptors Human genes 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 230000030648 nucleus localization Effects 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 230000001323 posttranslational effect Effects 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 239000011535 reaction buffer Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000002976 reverse transcriptase assay Methods 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 150000007970 thio esters Chemical class 0.000 description 3
- 108091006106 transcriptional activators Proteins 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 108010054220 vasodilator-stimulated phosphoprotein Proteins 0.000 description 3
- 230000029812 viral genome replication Effects 0.000 description 3
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 description 2
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 2
- KXALDPMLWMNCBR-UHFFFAOYSA-N 2-thiophen-2-yl-4-(thiophen-2-ylmethylidene)-1,3-oxazol-5-one Chemical compound O=C1OC(C=2SC=CC=2)=NC1=CC1=CC=CS1 KXALDPMLWMNCBR-UHFFFAOYSA-N 0.000 description 2
- NNMALANKTSRILL-LXENMSTPSA-N 3-[(2z,5e)-2-[[3-(2-carboxyethyl)-5-[(z)-[(3e,4r)-3-ethylidene-4-methyl-5-oxopyrrolidin-2-ylidene]methyl]-4-methyl-1h-pyrrol-2-yl]methylidene]-5-[(4-ethyl-3-methyl-5-oxopyrrol-2-yl)methylidene]-4-methylpyrrol-3-yl]propanoic acid Chemical compound O=C1C(CC)=C(C)C(\C=C\2C(=C(CCC(O)=O)C(=C/C3=C(C(C)=C(\C=C/4\C(\[C@@H](C)C(=O)N\4)=C\C)N3)CCC(O)=O)/N/2)C)=N1 NNMALANKTSRILL-LXENMSTPSA-N 0.000 description 2
- WDBQJSCPCGTAFG-QHCPKHFHSA-N 4,4-difluoro-N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-pyridin-3-ylpropyl]cyclohexane-1-carboxamide Chemical compound FC1(CCC(CC1)C(=O)N[C@@H](CCN1CCC(CC1)N1C(=NN=C1C)C(C)C)C=1C=NC=CC=1)F WDBQJSCPCGTAFG-QHCPKHFHSA-N 0.000 description 2
- 102100027211 Albumin Human genes 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 208000037259 Amyloid Plaque Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102100032307 BTB/POZ domain-containing adapter for CUL3-mediated RhoA degradation protein 3 Human genes 0.000 description 2
- 241000714266 Bovine leukemia virus Species 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- 101100539484 Caenorhabditis elegans unc-84 gene Proteins 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 101000637625 Cricetulus griseus GTP-binding protein SAR1b Proteins 0.000 description 2
- 101710201734 E3 protein Proteins 0.000 description 2
- 201000011001 Ebola Hemorrhagic Fever Diseases 0.000 description 2
- 241000713730 Equine infectious anemia virus Species 0.000 description 2
- 108010089790 Eukaryotic Initiation Factor-3 Proteins 0.000 description 2
- 102100037115 Eukaryotic translation initiation factor 3 subunit H Human genes 0.000 description 2
- 241000714165 Feline leukemia virus Species 0.000 description 2
- 108010028690 Fish Proteins Proteins 0.000 description 2
- 102100032174 GTP-binding protein SAR1a Human genes 0.000 description 2
- 101710177291 Gag polyprotein Proteins 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 102100024013 Golgi SNAP receptor complex member 2 Human genes 0.000 description 2
- 101710161767 Golgi resident protein GCP60 Proteins 0.000 description 2
- 102100033415 Golgi resident protein GCP60 Human genes 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- 101000798319 Homo sapiens BTB/POZ domain-containing adapter for CUL3-mediated RhoA degradation protein 3 Proteins 0.000 description 2
- 101000637622 Homo sapiens GTP-binding protein SAR1a Proteins 0.000 description 2
- 101000904234 Homo sapiens Golgi SNAP receptor complex member 2 Proteins 0.000 description 2
- 101000994792 Homo sapiens Ras GTPase-activating-like protein IQGAP1 Proteins 0.000 description 2
- 101001130465 Homo sapiens Ras-related protein Ral-A Proteins 0.000 description 2
- 101001087418 Homo sapiens Tyrosine-protein phosphatase non-receptor type 12 Proteins 0.000 description 2
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 description 2
- 241000714259 Human T-lymphotropic virus 2 Species 0.000 description 2
- 102100023408 KH domain-containing, RNA-binding, signal transduction-associated protein 1 Human genes 0.000 description 2
- 101710094958 KH domain-containing, RNA-binding, signal transduction-associated protein 1 Proteins 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 239000012097 Lipofectamine 2000 Substances 0.000 description 2
- 241001115401 Marburgvirus Species 0.000 description 2
- 241000713869 Moloney murine leukemia virus Species 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 239000000020 Nitrocellulose Substances 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- 108091005461 Nucleic proteins Proteins 0.000 description 2
- 108700020796 Oncogene Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108010068086 Polyubiquitin Proteins 0.000 description 2
- 102100037935 Polyubiquitin-C Human genes 0.000 description 2
- 102000029797 Prion Human genes 0.000 description 2
- 108091000054 Prion Proteins 0.000 description 2
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 102100031424 Ras-related protein Ral-A Human genes 0.000 description 2
- 108091007354 SIAHs Proteins 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229930182558 Sterol Natural products 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102100033020 Tyrosine-protein phosphatase non-receptor type 12 Human genes 0.000 description 2
- 241000710886 West Nile virus Species 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 230000001668 ameliorated effect Effects 0.000 description 2
- 108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 238000002820 assay format Methods 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000006369 cell cycle progression Effects 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 230000003822 cell turnover Effects 0.000 description 2
- 210000004671 cell-free system Anatomy 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 229960005156 digoxin Drugs 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 208000037765 diseases and disorders Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 238000007876 drug discovery Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 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 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 238000000799 fluorescence microscopy Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 229960003180 glutathione Drugs 0.000 description 2
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 2
- 210000002288 golgi apparatus Anatomy 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 238000003018 immunoassay Methods 0.000 description 2
- 238000001114 immunoprecipitation Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000012669 liquid formulation Substances 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 108020004084 membrane receptors Proteins 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000003068 molecular probe Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 229920001220 nitrocellulos Polymers 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000001566 pro-viral effect Effects 0.000 description 2
- 229940121649 protein inhibitor Drugs 0.000 description 2
- 239000012268 protein inhibitor Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 102000016731 rac GTP-Binding Proteins Human genes 0.000 description 2
- 108010092883 rac GTP-Binding Proteins Proteins 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000022983 regulation of cell cycle Effects 0.000 description 2
- 230000017610 release of virus from host Effects 0.000 description 2
- 230000003938 response to stress Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 150000003432 sterols Chemical class 0.000 description 2
- 235000003702 sterols Nutrition 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- ASWVTGNCAZCNNR-UHFFFAOYSA-N sulfamethazine Chemical compound CC1=CC(C)=NC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 ASWVTGNCAZCNNR-UHFFFAOYSA-N 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 230000007486 viral budding Effects 0.000 description 2
- 230000007502 viral entry Effects 0.000 description 2
- 239000011534 wash buffer Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- SLLFVLKNXABYGI-UHFFFAOYSA-N 1,2,3-benzoxadiazole Chemical compound C1=CC=C2ON=NC2=C1 SLLFVLKNXABYGI-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-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
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
- RNTCWULFNYNFGI-UHFFFAOYSA-N 1-(2,3-dihydroindol-1-yl)ethanone Chemical compound C1=CC=C2N(C(=O)C)CCC2=C1 RNTCWULFNYNFGI-UHFFFAOYSA-N 0.000 description 1
- QNFXLCHANYHGIF-UHFFFAOYSA-N 1-acetyl-2,3-dihydroindole-5-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C2N(C(=O)C)CCC2=C1 QNFXLCHANYHGIF-UHFFFAOYSA-N 0.000 description 1
- 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 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- GPWNWKWQOLEVEQ-UHFFFAOYSA-N 2,4-diaminopyrimidine-5-carbaldehyde Chemical compound NC1=NC=C(C=O)C(N)=N1 GPWNWKWQOLEVEQ-UHFFFAOYSA-N 0.000 description 1
- NXTJGIBOVGESBV-UHFFFAOYSA-N 2-(thiophene-2-carbonylamino)acetic acid Chemical compound OC(=O)CNC(=O)C1=CC=CS1 NXTJGIBOVGESBV-UHFFFAOYSA-N 0.000 description 1
- GHCFWKFREBNSPC-UHFFFAOYSA-N 2-Amino-4-methylpyrimidine Chemical compound CC1=CC=NC(N)=N1 GHCFWKFREBNSPC-UHFFFAOYSA-N 0.000 description 1
- CFBILACNYSPRPM-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;2-[[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]amino]acetic acid Chemical compound OCC(N)(CO)CO.OCC(CO)(CO)NCC(O)=O CFBILACNYSPRPM-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- BNBQQYFXBLBYJK-UHFFFAOYSA-N 2-pyridin-2-yl-1,3-oxazole Chemical compound C1=COC(C=2N=CC=CC=2)=N1 BNBQQYFXBLBYJK-UHFFFAOYSA-N 0.000 description 1
- LECKKBMOOVJZMV-UHFFFAOYSA-N 2-pyrimidin-2-ylbenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1C1=NC=CC=N1 LECKKBMOOVJZMV-UHFFFAOYSA-N 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 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
- 241000251468 Actinopterygii Species 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 description 1
- 241000607620 Aliivibrio fischeri Species 0.000 description 1
- 101000935845 Aliivibrio fischeri Blue fluorescence protein Proteins 0.000 description 1
- 241000710929 Alphavirus Species 0.000 description 1
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 1
- 102000014303 Amyloid beta-Protein Precursor Human genes 0.000 description 1
- 108010079054 Amyloid beta-Protein Precursor Proteins 0.000 description 1
- 102000018430 Amyloid-beta precursor proteins Human genes 0.000 description 1
- 108050007552 Amyloid-beta precursor proteins Proteins 0.000 description 1
- 241000242757 Anthozoa Species 0.000 description 1
- 240000003291 Armoracia rusticana Species 0.000 description 1
- 235000011330 Armoracia rusticana Nutrition 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 230000007082 Aβ accumulation Effects 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 1
- 125000005865 C2-C10alkynyl group Chemical group 0.000 description 1
- 108091007381 CBL proteins Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 235000014653 Carica parviflora Nutrition 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- WXNHTRQTJJLYTM-XMHGGMMESA-N Cc(cc(cc1)S(Nc2ncccn2)(=O)=O)c1NC(/C(/NC(c1ccc[s]1)=O)=C\c1ccc[s]1)=O Chemical compound Cc(cc(cc1)S(Nc2ncccn2)(=O)=O)c1NC(/C(/NC(c1ccc[s]1)=O)=C\c1ccc[s]1)=O WXNHTRQTJJLYTM-XMHGGMMESA-N 0.000 description 1
- APLTZGGOHIJIGB-XSFVSMFZSA-N Cc1nc(NS(c(cc2)ccc2NC(/C(/NC(c2ccc[s]2)=O)=C\c2ccc[s]2)=O)(=O)=O)nc(C)c1 Chemical compound Cc1nc(NS(c(cc2)ccc2NC(/C(/NC(c2ccc[s]2)=O)=C\c2ccc[s]2)=O)(=O)=O)nc(C)c1 APLTZGGOHIJIGB-XSFVSMFZSA-N 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 241000178041 Ceropegia media Species 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 241000709687 Coxsackievirus Species 0.000 description 1
- 241000700108 Ctenophora <comb jellyfish phylum> Species 0.000 description 1
- 241000192700 Cyanobacteria Species 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 241000725619 Dengue virus Species 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 108050002772 E3 ubiquitin-protein ligase Mdm2 Proteins 0.000 description 1
- 102000012199 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 description 1
- 102100029211 E3 ubiquitin-protein ligase TTC3 Human genes 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 241000709661 Enterovirus Species 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 101000935842 Escherichia coli O127:H6 (strain E2348/69 / EPEC) Major structural subunit of bundle-forming pilus Proteins 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 102100039556 Galectin-4 Human genes 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 108010010369 HIV Protease Proteins 0.000 description 1
- 108010078851 HIV Reverse Transcriptase Proteins 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 241000709721 Hepatovirus A Species 0.000 description 1
- 101000633723 Homo sapiens E3 ubiquitin-protein ligase TTC3 Proteins 0.000 description 1
- 101000608765 Homo sapiens Galectin-4 Proteins 0.000 description 1
- 101001057305 Homo sapiens Microtubule-associated protein 1S Proteins 0.000 description 1
- 101001079872 Homo sapiens RING finger protein 112 Proteins 0.000 description 1
- 101000821100 Homo sapiens Synapsin-1 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 208000033892 Hyperhomocysteinemia Diseases 0.000 description 1
- 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 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 208000029400 Inclusion myopathy Diseases 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000004890 Interleukin-8 Human genes 0.000 description 1
- 108090001007 Interleukin-8 Proteins 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
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 101710125418 Major capsid protein Proteins 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 241000712079 Measles morbillivirus Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102100027228 Microtubule-associated protein 1S Human genes 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 241000711386 Mumps virus Species 0.000 description 1
- 101100533424 Mus musculus Sh3rf1 gene Proteins 0.000 description 1
- 208000029578 Muscle disease Diseases 0.000 description 1
- 241000282339 Mustela Species 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
- 108010052419 NF-KappaB Inhibitor alpha Proteins 0.000 description 1
- 102100039337 NF-kappa-B inhibitor alpha Human genes 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- SEEPANYCNGTZFQ-UHFFFAOYSA-N Nc(cc1)ccc1S(Nc1ncccn1)(=O)=O Chemical compound Nc(cc1)ccc1S(Nc1ncccn1)(=O)=O SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 description 1
- 208000014060 Niemann-Pick disease Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 241000369774 Norwalk-like virus Species 0.000 description 1
- PENRZFCUHJBZHQ-NBVRZTHBSA-N O=C(/C(/NC(c1ccc[s]1)=O)=C\c1ccc[s]1)Nc(cc1)ccc1S(Nc1ncccn1)(=O)=O Chemical compound O=C(/C(/NC(c1ccc[s]1)=O)=C\c1ccc[s]1)Nc(cc1)ccc1S(Nc1ncccn1)(=O)=O PENRZFCUHJBZHQ-NBVRZTHBSA-N 0.000 description 1
- KXALDPMLWMNCBR-VQHVLOKHSA-N O=C1OC(c2ccc[s]2)=N/C1=C/c1ccc[s]1 Chemical compound O=C1OC(c2ccc[s]2)=N/C1=C/c1ccc[s]1 KXALDPMLWMNCBR-VQHVLOKHSA-N 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 241000713112 Orthobunyavirus Species 0.000 description 1
- 241000150452 Orthohantavirus Species 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 101000579647 Penaeus vannamei Penaeidin-2a Proteins 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 101710122592 Peridinin-chlorophyll a-binding protein Proteins 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 102000011420 Phospholipase D Human genes 0.000 description 1
- 108090000553 Phospholipase D Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 108010053210 Phycocyanin Proteins 0.000 description 1
- 108010004729 Phycoerythrin Proteins 0.000 description 1
- 208000024571 Pick disease Diseases 0.000 description 1
- 241000709664 Picornaviridae Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
- 229940079156 Proteasome inhibitor Drugs 0.000 description 1
- 102000055251 Proto-Oncogene Proteins c-cbl Human genes 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 241000711798 Rabies lyssavirus Species 0.000 description 1
- 241000712907 Retroviridae Species 0.000 description 1
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
- 241000713124 Rift Valley fever virus Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000710799 Rubella virus Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 241000242583 Scyphozoa Species 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 229940122055 Serine protease inhibitor Drugs 0.000 description 1
- 101710102218 Serine protease inhibitor Proteins 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
- 229920002472 Starch Polymers 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 241000200261 Symbiodinium Species 0.000 description 1
- 241000200270 Symbiodinium sp. Species 0.000 description 1
- 102100021905 Synapsin-1 Human genes 0.000 description 1
- 241000192707 Synechococcus Species 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 241000656145 Thyrsites atun Species 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 206010044688 Trisomy 21 Diseases 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 108010005705 Ubiquitinated Proteins Proteins 0.000 description 1
- 241000710772 Yellow fever virus Species 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
- 230000007488 abnormal function Effects 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 239000003570 air Substances 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
- 239000003513 alkali Substances 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 101150089041 aph-1 gene Proteins 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 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
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 229940093761 bile salts Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 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
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 238000012832 cell culture technique Methods 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000033366 cell cycle process Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 210000003850 cellular structure Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 239000005081 chemiluminescent agent Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 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
- GJQPMPFPNINLKP-UHFFFAOYSA-N diclofenamide Chemical compound NS(=O)(=O)C1=CC(Cl)=C(Cl)C(S(N)(=O)=O)=C1 GJQPMPFPNINLKP-UHFFFAOYSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 1
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical class [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical class O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 238000007878 drug screening assay Methods 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000005014 ectopic expression Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000002337 electrophoretic mobility shift assay Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 230000001973 epigenetic effect Effects 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- GWQVMPWSEVRGPY-UHFFFAOYSA-N europium cryptate Chemical compound [Eu+3].N=1C2=CC=CC=1CN(CC=1N=C(C=CC=1)C=1N=C(C3)C=CC=1)CC(N=1)=CC(C(=O)NCCN)=CC=1C(N=1)=CC(C(=O)NCCN)=CC=1CN3CC1=CC=CC2=N1 GWQVMPWSEVRGPY-UHFFFAOYSA-N 0.000 description 1
- 230000005281 excited state Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000028023 exocytosis Effects 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical class O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 230000009454 functional inhibition Effects 0.000 description 1
- IECPWNUMDGFDKC-MZJAQBGESA-N fusidic acid Chemical class O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C(O)=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C IECPWNUMDGFDKC-MZJAQBGESA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000003209 gene knockout Methods 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000005182 global health Effects 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000012203 high throughput assay Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 230000003225 hyperhomocysteinemia Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000012405 in silico analysis Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 201000008319 inclusion body myositis Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 208000037797 influenza A Diseases 0.000 description 1
- 208000037798 influenza B Diseases 0.000 description 1
- 208000037799 influenza C Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 1
- 229940096397 interleukin-8 Drugs 0.000 description 1
- 230000009878 intermolecular interaction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- DLBFLQKQABVKGT-UHFFFAOYSA-L lucifer yellow dye Chemical compound [Li+].[Li+].[O-]S(=O)(=O)C1=CC(C(N(C(=O)NN)C2=O)=O)=C3C2=CC(S([O-])(=O)=O)=CC3=C1N DLBFLQKQABVKGT-UHFFFAOYSA-L 0.000 description 1
- 208000025036 lymphosarcoma Diseases 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000006249 magnetic particle Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- FDZZZRQASAIRJF-UHFFFAOYSA-M malachite green Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1C(C=1C=CC=CC=1)=C1C=CC(=[N+](C)C)C=C1 FDZZZRQASAIRJF-UHFFFAOYSA-M 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
- 210000004962 mammalian cell Anatomy 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 235000019988 mead Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000034217 membrane fusion Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 238000001466 metabolic labeling Methods 0.000 description 1
- 125000005341 metaphosphate group Chemical group 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000011812 mixed powder Substances 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 238000000329 molecular dynamics simulation Methods 0.000 description 1
- 230000004784 molecular pathogenesis Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 108091005763 multidomain proteins Proteins 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 229940105132 myristate Drugs 0.000 description 1
- 125000001419 myristoyl group Chemical group O=C([*])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
- ISKWOQDJOISDFV-UHFFFAOYSA-N n-(4-methylpyrimidin-2-yl)-2,3-dihydro-1h-indole-5-sulfonamide Chemical compound CC1=CC=NC(NS(=O)(=O)C=2C=C3CCNC3=CC=2)=N1 ISKWOQDJOISDFV-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 102000046701 nicastrin Human genes 0.000 description 1
- 108700022821 nicastrin Proteins 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000000082 organ preservation Substances 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000816 peptidomimetic Substances 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 230000000079 pharmacotherapeutic effect Effects 0.000 description 1
- 229940049953 phenylacetate 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
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 208000026689 polyglucosan body myopathy Diseases 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000034190 positive regulation of NF-kappaB transcription factor activity Effects 0.000 description 1
- 230000006555 post-translational control Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 239000003207 proteasome inhibitor Substances 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000002441 reversible effect Effects 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
- 108091092562 ribozyme Proteins 0.000 description 1
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 230000000698 schizophrenic effect Effects 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000009991 scouring Methods 0.000 description 1
- 229940116351 sebacate Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000009962 secretion pathway Effects 0.000 description 1
- 230000008684 selective degradation Effects 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 102000030938 small GTPase Human genes 0.000 description 1
- 108060007624 small GTPase Proteins 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- ZNJHFNUEQDVFCJ-UHFFFAOYSA-M sodium;2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid;hydroxide Chemical compound [OH-].[Na+].OCCN1CCN(CCS(O)(=O)=O)CC1 ZNJHFNUEQDVFCJ-UHFFFAOYSA-M 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000002904 solvent 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
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 208000023516 stroke disease Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000003774 sulfhydryl reagent Substances 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
- QIQITDHWZYEEPA-UHFFFAOYSA-N thiophene-2-carbonyl chloride Chemical compound ClC(=O)C1=CC=CS1 QIQITDHWZYEEPA-UHFFFAOYSA-N 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 238000010396 two-hybrid screening Methods 0.000 description 1
- 108010084736 ubiquitin carrier proteins Proteins 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 210000003934 vacuole Anatomy 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000007332 vesicle formation Effects 0.000 description 1
- 230000028973 vesicle-mediated transport Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000010463 virion release Effects 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 238000001086 yeast two-hybrid system Methods 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Virology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US85737806P | 2006-11-07 | 2006-11-07 | |
| US95983107P | 2007-07-17 | 2007-07-17 | |
| PCT/IL2007/001356 WO2008056356A2 (en) | 2006-11-07 | 2007-11-07 | Pyrimidine derivatives as posh and posh-ap inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010509205A true JP2010509205A (ja) | 2010-03-25 |
| JP2010509205A5 JP2010509205A5 (enExample) | 2010-12-24 |
Family
ID=39364907
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009535189A Pending JP2010509205A (ja) | 2006-11-07 | 2007-11-07 | Ｐｏｓｈ及びｐｏｓｈ−ａｐ阻害剤としてのピリミジン誘導体 |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US8283355B2 (enExample) |
| EP (1) | EP2083826A4 (enExample) |
| JP (1) | JP2010509205A (enExample) |
| AU (1) | AU2007318922C1 (enExample) |
| CA (1) | CA2668859A1 (enExample) |
| WO (1) | WO2008056356A2 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20120116425A (ko) * | 2009-11-30 | 2012-10-22 | 프로테오로직스 엘티디 | 작은 피리미딘 유도체 및 이의 사용 방법 |
| WO2013088445A1 (en) * | 2011-12-13 | 2013-06-20 | Proteologics Ltd | Pyrimidine derivatives for treatment of inflammatory diseases |
| GB201415688D0 (en) * | 2014-09-04 | 2014-10-22 | Univ Edinburgh | Method and Systems |
| SG10201913958QA (en) * | 2015-07-15 | 2020-03-30 | Agency Science Tech & Res | Modulation of hepatitis b virus replication |
| WO2018085208A1 (en) | 2016-11-02 | 2018-05-11 | The Research Foundation For The State University Of New York | Methods of inhibiting viruses using compositions targeting tsg101-ubiquitin interaction |
| MA53086B1 (fr) * | 2018-07-05 | 2024-07-31 | Bayer Aktiengesellschaft | Thiophènecarboxamides substitués et analogues comme agents antibactériens |
| US20220193041A1 (en) * | 2019-04-02 | 2022-06-23 | Yonsei University, University - Industry Foundation (UIF) | Novel compound and method for preventing or treating of respiratory diseases comprising the same as an active ingredient |
| CN110760597B (zh) * | 2019-11-22 | 2022-08-23 | 西北农林科技大学 | 一种检测黄牛ncstn基因拷贝数变异的方法及其应用 |
| TW202527955A (zh) * | 2023-11-27 | 2025-07-16 | 美商尼坎醫療公司 | 用於經由泛素蛋白酶體途徑降解週期蛋白依賴性激酶２和週期蛋白依賴性激酶４的含有２，５－取代的嘧啶衍生物的雙功能化合物 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005013914A2 (en) * | 2003-08-08 | 2005-02-17 | Vertex Pharmaceuticals Incorporated | Heteroarylaminosulfonylphenyl derivatives for use as sodium or calcium channel blockers in the treatment of pain |
| US20060014807A1 (en) * | 2004-07-19 | 2006-01-19 | Lin Leu-Fen H | Neuroprotective small organic molecules, compositions and uses related thereto |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5734081A (en) | 1994-08-05 | 1998-03-31 | Warner-Lambert Company | Arylthio compounds |
| JP2004515235A (ja) | 2000-12-08 | 2004-05-27 | ノボ ノルディスク アクティーゼルスカブ | Ｔｆｆペプチド |
| FI116940B (fi) | 2001-07-20 | 2006-04-13 | Juvantia Pharma Ltd Oy | Alfa-2B-adrenoseptorivälitteisen sairauden hoitoon tai ehkäisyyn käyttökelpoiset yhdisteet |
| CA2456754A1 (en) * | 2001-08-08 | 2003-02-20 | Yuji Iizawa | Benzazepine derivative, process for producing the same, and use |
| FR2845382A1 (fr) | 2002-10-02 | 2004-04-09 | Sanofi Synthelabo | Derives d'indazolecarboxamides, leur preparation et leur utilisation en therapeutique |
| US20050214751A1 (en) | 2004-03-02 | 2005-09-29 | Proteologics, Inc. | Inhibition of viral maturation, methods and compositions related thereto |
-
2007
- 2007-11-07 AU AU2007318922A patent/AU2007318922C1/en not_active Ceased
- 2007-11-07 EP EP07827329A patent/EP2083826A4/en not_active Withdrawn
- 2007-11-07 CA CA002668859A patent/CA2668859A1/en not_active Abandoned
- 2007-11-07 WO PCT/IL2007/001356 patent/WO2008056356A2/en not_active Ceased
- 2007-11-07 US US12/312,416 patent/US8283355B2/en not_active Expired - Fee Related
- 2007-11-07 JP JP2009535189A patent/JP2010509205A/ja active Pending
-
2012
- 2012-10-04 US US13/645,465 patent/US20130131094A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005013914A2 (en) * | 2003-08-08 | 2005-02-17 | Vertex Pharmaceuticals Incorporated | Heteroarylaminosulfonylphenyl derivatives for use as sodium or calcium channel blockers in the treatment of pain |
| US20060014807A1 (en) * | 2004-07-19 | 2006-01-19 | Lin Leu-Fen H | Neuroprotective small organic molecules, compositions and uses related thereto |
Non-Patent Citations (4)
| Title |
|---|
| JPN6013000717; 'Ｓｙｎｔｈｅｓｉｓ ｏｆ ｓｏｍｅ ｎｅｗ ｈｅｔｅｒｏｂｉｃｙｃｌｉｃ ｃｏｍｐｏｕｎｄ ｂｅａｒｉｎｇ ｃｈｒｏｍｏｎ-３-ｙｌ ｍｏｉｅｔｙ ａｎｄ ｒｅｌａｔｅｄ ｃｏｍｐｏｕｎｄａ ａｓ ａ' Ｃｈｅｍｉｃａｌ ａｂｓｔｒａｃｔｓ Ｖｏｌ．１２７, 1997, ３４１７０ｈ，３４１７１ａ * |
| JPN6013000719; Ｒｅｇｉｓｔｒｙ Ｎｏ．３２６０２６-７５-９，Ｒｅｇｉｓｔｒｙ ［ｏｎｌｉｎｅ］； Ｒｅｔｒｉｅｖｅｄ ｆｒｏｍ ＳＴＮ , 20010307 * |
| JPN6013000721; Ｊｏｕｒｎａｌ ｏｆ Ｃｏｍｂｉｎａｔｏｒｉａｌ Ｃｈｅｍｉｓｔｒｙ Ｖｏｌ．８， Ｎｏ．３, 2006, ｐ．３２６-３３７ * |
| JPN6013000723; Ｓｕｌｆｕｒ Ｌｅｔｔｅｒｓ Ｖｏｌ．２４， Ｎｏ．４, 2001, ｐ．１５１-１７９ * |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2083826A4 (en) | 2010-09-22 |
| AU2007318922B2 (en) | 2013-01-10 |
| US8283355B2 (en) | 2012-10-09 |
| AU2007318922C1 (en) | 2013-09-12 |
| WO2008056356A3 (en) | 2009-09-03 |
| CA2668859A1 (en) | 2008-05-15 |
| WO2008056356A2 (en) | 2008-05-15 |
| EP2083826A2 (en) | 2009-08-05 |
| AU2007318922A1 (en) | 2008-05-15 |
| US20130131094A1 (en) | 2013-05-23 |
| US20100179178A1 (en) | 2010-07-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20130131094A1 (en) | Pyrimidine derivatives as posh and posh-ap inhibitors | |
| US7323490B2 (en) | Pyrrole compounds and uses thereof | |
| Agola et al. | A competitive nucleotide binding inhibitor: in vitro characterization of Rab7 GTPase inhibition | |
| US20120135089A1 (en) | E3 ligase inhibitors | |
| US20050059628A1 (en) | Modulation of beta-catenin/TCF-activated transcription | |
| DK2780326T3 (en) | PROCEDURE FOR INHIBITING DEUBIQUITINATION ACTIVITY | |
| Donkor | An update on the therapeutic potential of calpain inhibitors: a patent review | |
| Blaquiere et al. | Medicinal chemistry of inhibiting RING-type E3 ubiquitin ligases | |
| CN114025766B (zh) | 用于抑制gapdh的噁噻嗪化合物 | |
| JP2021167301A (ja) | Ｃｄｋ２阻害剤に対する腫瘍適応を抑制するためのｃｄｋ４／６およびｃｄｋ２阻害剤による同時処置 | |
| US20120015967A1 (en) | Pyrimidine and pyridine derivatives as posh and posh-ap inhibitors | |
| CN111670188B (zh) | 用于治疗纤维化的化合物和组合物 | |
| AU2005279845A1 (en) | Inhibition of viruses using RNase H inhibitors | |
| EP1646644A2 (en) | Posh interacting proteins and related methods | |
| KR20220142363A (ko) | 선택적 mTORC2 저해제 및 이의 용도 | |
| QUEZADA MEZA | PROTEIN KINASE CK2 IN HUMAN DISEASES: TOO MUCH OR TOO LITTLE? | |
| CN109790523A (zh) | 组合物及其用途 | |
| MX2007013738A (es) | Derivados de pirimidilaminobenzamida para sindrome hipereosinofilico. | |
| 하재영 | Development and applications of thermal stability shift-based methodology for label-free target protein identification | |
| US20060286630A1 (en) | Posh interacting proteins and related methods | |
| Sanna | Design, synthesis and biological evaluation of pyrazolo-pyrimidines and related isosteres as inhibitors of protein kinases, potential antineoplastic agents | |
| TW201217341A (en) | Receptor-type kinase modulator and methods of treating polycystic kidney disease | |
| Birsa | Mitochondrial transport regulation in Parkinson’s disease | |
| Metcalf et al. | Targeting Protein Kinases for Bone Disease: Discovery and Development of Src Inhibitors | |
| Sroka | Effects of Roscovitine and Indirubin-derivatives on platelet derived growth factor signalling in vascular smooth muscle cells |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20101105 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20101105 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130111 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130411 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20130412 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130802 |