CA2487438A1

CA2487438A1 - Methods of treating and diagnosing diabetes with cx3cr1 modulators

Methods of treating and diagnosing diabetes with cx3cr1 modulators Download PDF

Info

Publication number: CA2487438A1
Authority: CA; Canada
Prior art keywords: cx3cr1; polypeptide; fractalkine; seq; cell
Prior art date: 2002-06-10
Legal status : Abandoned

Application number

CA002487438A

Other languages

English (en)

French (fr)

Inventor

Shonna Moodie

Thomas A. Gustafson

Current Assignee

CymaBay Therapeutics Inc

Original Assignee

Individual

Priority date

2002-06-10

Filing date

2003-06-10

Publication date

2003-12-18

2003-06-10 Application filed by Individual filed Critical Individual

2003-12-18 Publication of CA2487438A1 publication Critical patent/CA2487438A1/en

Status Abandoned legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 197
206010012601 diabetes mellitus Diseases 0.000 title claims abstract description 99
102100039196 CX3C chemokine receptor 1 Human genes 0.000 claims abstract description 253
108010078239 Chemokine CX3CL1 Proteins 0.000 claims abstract description 207
208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 31
206010022489 Insulin Resistance Diseases 0.000 claims abstract description 28
108090000835 CX3C Chemokine Receptor 1 Proteins 0.000 claims abstract 18
210000004027 cell Anatomy 0.000 claims description 184
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 168
108090000765 processed proteins & peptides Proteins 0.000 claims description 140
102000004196 processed proteins & peptides Human genes 0.000 claims description 124
150000007523 nucleic acids Chemical class 0.000 claims description 116
229920001184 polypeptide Polymers 0.000 claims description 115
102000039446 nucleic acids Human genes 0.000 claims description 106
108020004707 nucleic acids Proteins 0.000 claims description 106
239000000523 sample Substances 0.000 claims description 99
230000000694 effects Effects 0.000 claims description 98
230000014509 gene expression Effects 0.000 claims description 90
102000004877 Insulin Human genes 0.000 claims description 85
108090001061 Insulin Proteins 0.000 claims description 85
229940125396 insulin Drugs 0.000 claims description 84
239000003795 chemical substances by application Substances 0.000 claims description 68
230000027455 binding Effects 0.000 claims description 57
238000009739 binding Methods 0.000 claims description 57
239000003446 ligand Substances 0.000 claims description 50
102000040430 polynucleotide Human genes 0.000 claims description 47
108091033319 polynucleotide Proteins 0.000 claims description 47
239000002157 polynucleotide Substances 0.000 claims description 47
125000003275 alpha amino acid group Chemical group 0.000 claims description 44
210000001519 tissue Anatomy 0.000 claims description 36
238000012360 testing method Methods 0.000 claims description 33
241001465754 Metazoa Species 0.000 claims description 31
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 29
239000012634 fragment Substances 0.000 claims description 29
239000008103 glucose Substances 0.000 claims description 29
238000003752 polymerase chain reaction Methods 0.000 claims description 29
108020004999 messenger RNA Proteins 0.000 claims description 27
239000008280 blood Substances 0.000 claims description 26
210000004369 blood Anatomy 0.000 claims description 26
206010018429 Glucose tolerance impaired Diseases 0.000 claims description 22
241000282414 Homo sapiens Species 0.000 claims description 22
210000001789 adipocyte Anatomy 0.000 claims description 21
230000001965 increasing effect Effects 0.000 claims description 20
102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 claims description 19
238000000338 in vitro Methods 0.000 claims description 15
108091054455 MAP kinase family Proteins 0.000 claims description 13
102000043136 MAP kinase family Human genes 0.000 claims description 13
230000026731 phosphorylation Effects 0.000 claims description 12
238000006366 phosphorylation reaction Methods 0.000 claims description 12
108091000080 Phosphotransferase Proteins 0.000 claims description 10
102000020233 phosphotransferase Human genes 0.000 claims description 10
108091008611 Protein Kinase B Proteins 0.000 claims description 9
239000013603 viral vector Substances 0.000 claims description 9
210000002700 urine Anatomy 0.000 claims description 7
102000058061 Glucose Transporter Type 4 Human genes 0.000 claims description 6
108091006300 SLC2A4 Proteins 0.000 claims description 6
239000012472 biological sample Substances 0.000 claims description 6
108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 claims description 6
230000002441 reversible effect Effects 0.000 claims description 6
101100457333 Homo sapiens MAPK11 gene Proteins 0.000 claims description 5
108700036166 Mitogen-Activated Protein Kinase 11 Proteins 0.000 claims description 5
102100026929 Mitogen-activated protein kinase 11 Human genes 0.000 claims description 5
101150046814 SAPK2 gene Proteins 0.000 claims description 5
230000003247 decreasing effect Effects 0.000 claims description 5
230000005945 translocation Effects 0.000 claims description 5
101000950669 Homo sapiens Mitogen-activated protein kinase 9 Proteins 0.000 claims description 4
102100037809 Mitogen-activated protein kinase 9 Human genes 0.000 claims description 4
210000005229 liver cell Anatomy 0.000 claims description 3
210000000601 blood cell Anatomy 0.000 claims description 2
230000003185 calcium uptake Effects 0.000 claims description 2
230000001747 exhibiting effect Effects 0.000 claims description 2
210000003296 saliva Anatomy 0.000 claims description 2
210000002363 skeletal muscle cell Anatomy 0.000 claims description 2
102000013818 Fractalkine Human genes 0.000 claims 4
101000950695 Homo sapiens Mitogen-activated protein kinase 8 Proteins 0.000 claims 2
102100037808 Mitogen-activated protein kinase 8 Human genes 0.000 claims 2
239000000203 mixture Substances 0.000 abstract description 38
102100020997 Fractalkine Human genes 0.000 abstract description 3
101000746022 Homo sapiens CX3C chemokine receptor 1 Proteins 0.000 description 241
102000014464 Chemokine CX3CL1 Human genes 0.000 description 200
108090000623 proteins and genes Proteins 0.000 description 188
102000004169 proteins and genes Human genes 0.000 description 150
235000018102 proteins Nutrition 0.000 description 143
238000003556 assay Methods 0.000 description 75
235000001014 amino acid Nutrition 0.000 description 47
229940024606 amino acid Drugs 0.000 description 46
239000013598 vector Substances 0.000 description 46
150000001875 compounds Chemical class 0.000 description 45
150000001413 amino acids Chemical group 0.000 description 44
238000009396 hybridization Methods 0.000 description 42
239000002773 nucleotide Substances 0.000 description 34
125000003729 nucleotide group Chemical group 0.000 description 33
239000013615 primer Substances 0.000 description 32
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 28
229960001031 glucose Drugs 0.000 description 28
102000019034 Chemokines Human genes 0.000 description 27
108010012236 Chemokines Proteins 0.000 description 27
108020003175 receptors Proteins 0.000 description 27
210000002027 skeletal muscle Anatomy 0.000 description 27
238000003018 immunoassay Methods 0.000 description 25
102000005962 receptors Human genes 0.000 description 25
239000000126 substance Substances 0.000 description 24
238000001514 detection method Methods 0.000 description 22
230000004913 activation Effects 0.000 description 21
239000000556 agonist Substances 0.000 description 21
239000007787 solid Substances 0.000 description 21
108020004414 DNA Proteins 0.000 description 20
102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 18
108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 18
239000012190 activator Substances 0.000 description 17
210000004379 membrane Anatomy 0.000 description 17
239000012528 membrane Substances 0.000 description 17
108020004459 Small interfering RNA Proteins 0.000 description 16
230000002163 immunogen Effects 0.000 description 16
238000012216 screening Methods 0.000 description 16
239000000758 substrate Substances 0.000 description 16
102000004190 Enzymes Human genes 0.000 description 15
108090000790 Enzymes Proteins 0.000 description 15
108091028043 Nucleic acid sequence Proteins 0.000 description 15
239000011230 binding agent Substances 0.000 description 15
229940088598 enzyme Drugs 0.000 description 15
238000001415 gene therapy Methods 0.000 description 15
239000003112 inhibitor Substances 0.000 description 15
-1 'y -carboxyglutamate Chemical compound 0.000 description 14
125000000539 amino acid group Chemical group 0.000 description 14
239000005557 antagonist Substances 0.000 description 14
238000004422 calculation algorithm Methods 0.000 description 14
230000019491 signal transduction Effects 0.000 description 14
108091032973 (ribonucleotides)n+m Proteins 0.000 description 13
241000699670 Mus sp. Species 0.000 description 13
230000007423 decrease Effects 0.000 description 13
238000012546 transfer Methods 0.000 description 13
108020004705 Codon Proteins 0.000 description 12
239000012491 analyte Substances 0.000 description 12
230000004190 glucose uptake Effects 0.000 description 12
238000002372 labelling Methods 0.000 description 12
230000003612 virological effect Effects 0.000 description 12
241000700605 Viruses Species 0.000 description 11
239000000872 buffer Substances 0.000 description 11
238000006243 chemical reaction Methods 0.000 description 11
239000003153 chemical reaction reagent Substances 0.000 description 11
239000002299 complementary DNA Substances 0.000 description 11
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
238000009472 formulation Methods 0.000 description 11
230000006870 function Effects 0.000 description 11
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 10
241000894006 Bacteria Species 0.000 description 10
241000702421 Dependoparvovirus Species 0.000 description 10
101000854520 Homo sapiens Fractalkine Proteins 0.000 description 10
235000005911 diet Nutrition 0.000 description 10
201000010099 disease Diseases 0.000 description 10
238000000159 protein binding assay Methods 0.000 description 10
238000006467 substitution reaction Methods 0.000 description 10
108091006027 G proteins Proteins 0.000 description 9
102000030782 GTP binding Human genes 0.000 description 9
108091000058 GTP-Binding Proteins 0.000 description 9
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 9
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 9
230000037213 diet Effects 0.000 description 9
239000003814 drug Substances 0.000 description 9
238000001727 in vivo Methods 0.000 description 9
230000003834 intracellular effect Effects 0.000 description 9
238000002493 microarray Methods 0.000 description 9
238000000746 purification Methods 0.000 description 9
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 8
101000854519 Mus musculus Fractalkine Proteins 0.000 description 8
108091005461 Nucleic proteins Proteins 0.000 description 8
101710113459 RAC-alpha serine/threonine-protein kinase Proteins 0.000 description 8
239000000427 antigen Substances 0.000 description 8
108091007433 antigens Proteins 0.000 description 8
102000036639 antigens Human genes 0.000 description 8
210000003000 inclusion body Anatomy 0.000 description 8
210000000265 leukocyte Anatomy 0.000 description 8
229920000642 polymer Polymers 0.000 description 8
230000004044 response Effects 0.000 description 8
238000012552 review Methods 0.000 description 8
239000003981 vehicle Substances 0.000 description 8
108700028369 Alleles Proteins 0.000 description 7
108700026244 Open Reading Frames Proteins 0.000 description 7
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 7
238000004458 analytical method Methods 0.000 description 7
230000015572 biosynthetic process Effects 0.000 description 7
210000001072 colon Anatomy 0.000 description 7
230000000295 complement effect Effects 0.000 description 7
229940079593 drug Drugs 0.000 description 7
102000057105 human CX3CL1 Human genes 0.000 description 7
238000011534 incubation Methods 0.000 description 7
150000002500 ions Chemical class 0.000 description 7
238000002360 preparation method Methods 0.000 description 7
230000001105 regulatory effect Effects 0.000 description 7
239000007790 solid phase Substances 0.000 description 7
239000000243 solution Substances 0.000 description 7
ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 6
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 6
238000000692 Student's t-test Methods 0.000 description 6
108091023040 Transcription factor Proteins 0.000 description 6
102000040945 Transcription factor Human genes 0.000 description 6
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 6
238000007792 addition Methods 0.000 description 6
229910052921 ammonium sulfate Inorganic materials 0.000 description 6
235000011130 ammonium sulphate Nutrition 0.000 description 6
210000004556 brain Anatomy 0.000 description 6
230000001413 cellular effect Effects 0.000 description 6
230000009260 cross reactivity Effects 0.000 description 6
238000003745 diagnosis Methods 0.000 description 6
230000002068 genetic effect Effects 0.000 description 6
230000001900 immune effect Effects 0.000 description 6
230000003993 interaction Effects 0.000 description 6
239000002502 liposome Substances 0.000 description 6
238000004519 manufacturing process Methods 0.000 description 6
150000003905 phosphatidylinositols Chemical class 0.000 description 6
239000013612 plasmid Substances 0.000 description 6
238000003753 real-time PCR Methods 0.000 description 6
230000001177 retroviral effect Effects 0.000 description 6
238000000926 separation method Methods 0.000 description 6
241000894007 species Species 0.000 description 6
230000000638 stimulation Effects 0.000 description 6
238000010361 transduction Methods 0.000 description 6
230000026683 transduction Effects 0.000 description 6
241000701161 unidentified adenovirus Species 0.000 description 6
238000001262 western blot Methods 0.000 description 6
MMWCIQZXVOZEGG-UHFFFAOYSA-N 1,4,5-IP3 Natural products OC1C(O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(O)C1OP(O)(O)=O MMWCIQZXVOZEGG-UHFFFAOYSA-N 0.000 description 5
MMWCIQZXVOZEGG-XJTPDSDZSA-N D-myo-Inositol 1,4,5-trisphosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H](O)[C@@H]1OP(O)(O)=O MMWCIQZXVOZEGG-XJTPDSDZSA-N 0.000 description 5
208000008589 Obesity Diseases 0.000 description 5
108091034117 Oligonucleotide Proteins 0.000 description 5
241000700159 Rattus Species 0.000 description 5
108700019146 Transgenes Proteins 0.000 description 5
JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 5
238000003491 array Methods 0.000 description 5
238000002820 assay format Methods 0.000 description 5
235000020958 biotin Nutrition 0.000 description 5
229960002685 biotin Drugs 0.000 description 5
239000011616 biotin Substances 0.000 description 5
230000000875 corresponding effect Effects 0.000 description 5
230000001186 cumulative effect Effects 0.000 description 5
230000001419 dependent effect Effects 0.000 description 5
210000003527 eukaryotic cell Anatomy 0.000 description 5
239000007850 fluorescent dye Substances 0.000 description 5
230000004927 fusion Effects 0.000 description 5
102000037865 fusion proteins Human genes 0.000 description 5
108020001507 fusion proteins Proteins 0.000 description 5
230000006377 glucose transport Effects 0.000 description 5
238000005259 measurement Methods 0.000 description 5
210000001616 monocyte Anatomy 0.000 description 5
210000000440 neutrophil Anatomy 0.000 description 5
238000007899 nucleic acid hybridization Methods 0.000 description 5
235000020824 obesity Nutrition 0.000 description 5
238000004806 packaging method and process Methods 0.000 description 5
239000008188 pellet Substances 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
239000000047 product Substances 0.000 description 5
150000003839 salts Chemical class 0.000 description 5
230000035945 sensitivity Effects 0.000 description 5
239000002904 solvent Substances 0.000 description 5
239000006228 supernatant Substances 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
230000001225 therapeutic effect Effects 0.000 description 5
238000011282 treatment Methods 0.000 description 5
241001430294 unidentified retrovirus Species 0.000 description 5
108091093088 Amplicon Proteins 0.000 description 4
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
102000009410 Chemokine receptor Human genes 0.000 description 4
108050000299 Chemokine receptor Proteins 0.000 description 4
108060003951 Immunoglobulin Proteins 0.000 description 4
108010021625 Immunoglobulin Fragments Proteins 0.000 description 4
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 4
241000283973 Oryctolagus cuniculus Species 0.000 description 4
102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 4
108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 4
101710182846 Polyhedrin Proteins 0.000 description 4
108010090804 Streptavidin Proteins 0.000 description 4
230000003213 activating effect Effects 0.000 description 4
239000013543 active substance Substances 0.000 description 4
230000003321 amplification Effects 0.000 description 4
238000013459 approach Methods 0.000 description 4
239000002585 base Substances 0.000 description 4
239000011324 bead Substances 0.000 description 4
230000008901 benefit Effects 0.000 description 4
229940049706 benzodiazepine Drugs 0.000 description 4
150000001557 benzodiazepines Chemical class 0.000 description 4
210000004899 c-terminal region Anatomy 0.000 description 4
229910052791 calcium Inorganic materials 0.000 description 4
239000011575 calcium Substances 0.000 description 4
210000000170 cell membrane Anatomy 0.000 description 4
230000008859 change Effects 0.000 description 4
238000003776 cleavage reaction Methods 0.000 description 4
238000010367 cloning Methods 0.000 description 4
238000002648 combination therapy Methods 0.000 description 4
238000012875 competitive assay Methods 0.000 description 4
230000009918 complex formation Effects 0.000 description 4
125000004122 cyclic group Chemical group 0.000 description 4
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
230000001086 cytosolic effect Effects 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
238000001502 gel electrophoresis Methods 0.000 description 4
239000011521 glass Substances 0.000 description 4
230000002209 hydrophobic effect Effects 0.000 description 4
102000018358 immunoglobulin Human genes 0.000 description 4
238000001802 infusion Methods 0.000 description 4
230000002401 inhibitory effect Effects 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
230000010354 integration Effects 0.000 description 4
125000005647 linker group Chemical group 0.000 description 4
150000002632 lipids Chemical class 0.000 description 4
238000001638 lipofection Methods 0.000 description 4
229930182817 methionine Natural products 0.000 description 4
238000003199 nucleic acid amplification method Methods 0.000 description 4
230000003287 optical effect Effects 0.000 description 4
239000000816 peptidomimetic Substances 0.000 description 4
239000008194 pharmaceutical composition Substances 0.000 description 4
230000002285 radioactive effect Effects 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
230000010076 replication Effects 0.000 description 4
230000007017 scission Effects 0.000 description 4
230000009870 specific binding Effects 0.000 description 4
210000000130 stem cell Anatomy 0.000 description 4
238000002560 therapeutic procedure Methods 0.000 description 4
238000001890 transfection Methods 0.000 description 4
238000013519 translation Methods 0.000 description 4
208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 4
241000701447 unidentified baculovirus Species 0.000 description 4
238000011179 visual inspection Methods 0.000 description 4
239000013607 AAV vector Substances 0.000 description 3
101150062345 CX3CR1 gene Proteins 0.000 description 3
101100220616 Caenorhabditis elegans chk-2 gene Proteins 0.000 description 3
108091026890 Coding region Proteins 0.000 description 3
102000004127 Cytokines Human genes 0.000 description 3
108090000695 Cytokines Proteins 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
241000238631 Hexapoda Species 0.000 description 3
241000725303 Human immunodeficiency virus Species 0.000 description 3
102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
108700005091 Immunoglobulin Genes Proteins 0.000 description 3
102100021244 Integral membrane protein GPR180 Human genes 0.000 description 3
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
241000124008 Mammalia Species 0.000 description 3
241000699666 Mus <mouse, genus> Species 0.000 description 3
238000000636 Northern blotting Methods 0.000 description 3
239000004677 Nylon Substances 0.000 description 3
101000746037 Rattus norvegicus CX3C chemokine receptor 1 Proteins 0.000 description 3
108700008625 Reporter Genes Proteins 0.000 description 3
229940123464 Thiazolidinedione Drugs 0.000 description 3
108060000200 adenylate cyclase Proteins 0.000 description 3
102000030621 adenylate cyclase Human genes 0.000 description 3
210000000577 adipose tissue Anatomy 0.000 description 3
239000002671 adjuvant Substances 0.000 description 3
235000004279 alanine Nutrition 0.000 description 3
230000000692 anti-sense effect Effects 0.000 description 3
230000000890 antigenic effect Effects 0.000 description 3
230000009460 calcium influx Effects 0.000 description 3
239000006285 cell suspension Substances 0.000 description 3
239000002975 chemoattractant Substances 0.000 description 3
230000001447 compensatory effect Effects 0.000 description 3
230000009137 competitive binding Effects 0.000 description 3
238000012217 deletion Methods 0.000 description 3
230000037430 deletion Effects 0.000 description 3
238000000502 dialysis Methods 0.000 description 3
239000013604 expression vector Substances 0.000 description 3
230000004907 flux Effects 0.000 description 3
238000005194 fractionation Methods 0.000 description 3
102000034345 heterotrimeric G proteins Human genes 0.000 description 3
108091006093 heterotrimeric G proteins Proteins 0.000 description 3
239000005556 hormone Substances 0.000 description 3
229940088597 hormone Drugs 0.000 description 3
102000051339 human CX3CR1 Human genes 0.000 description 3
230000028993 immune response Effects 0.000 description 3
230000001939 inductive effect Effects 0.000 description 3
108020001756 ligand binding domains Proteins 0.000 description 3
238000007834 ligase chain reaction Methods 0.000 description 3
230000002934 lysing effect Effects 0.000 description 3
210000004962 mammalian cell Anatomy 0.000 description 3
239000011159 matrix material Substances 0.000 description 3
230000010534 mechanism of action Effects 0.000 description 3
238000013508 migration Methods 0.000 description 3
238000010172 mouse model Methods 0.000 description 3
210000003205 muscle Anatomy 0.000 description 3
230000036963 noncompetitive effect Effects 0.000 description 3
229920001778 nylon Polymers 0.000 description 3
230000002018 overexpression Effects 0.000 description 3
239000002245 particle Substances 0.000 description 3
230000037361 pathway Effects 0.000 description 3
230000002093 peripheral effect Effects 0.000 description 3
210000001322 periplasm Anatomy 0.000 description 3
230000010287 polarization Effects 0.000 description 3
239000013641 positive control Substances 0.000 description 3
239000002987 primer (paints) Substances 0.000 description 3
230000000750 progressive effect Effects 0.000 description 3
238000011160 research Methods 0.000 description 3
238000012163 sequencing technique Methods 0.000 description 3
210000000952 spleen Anatomy 0.000 description 3
238000010561 standard procedure Methods 0.000 description 3
238000005406 washing Methods 0.000 description 3
VRYALKFFQXWPIH-PBXRRBTRSA-N (3r,4s,5r)-3,4,5,6-tetrahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)CC=O VRYALKFFQXWPIH-PBXRRBTRSA-N 0.000 description 2
102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
PMMURAAUARKVCB-CERMHHMHSA-N 2-deoxy-D-glucopyranose Chemical compound OC[C@H]1OC(O)C[C@@H](O)[C@@H]1O PMMURAAUARKVCB-CERMHHMHSA-N 0.000 description 2
HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
108020004774 Alkaline Phosphatase Proteins 0.000 description 2
102000002260 Alkaline Phosphatase Human genes 0.000 description 2
201000001320 Atherosclerosis Diseases 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
102000001902 CC Chemokines Human genes 0.000 description 2
108010040471 CC Chemokines Proteins 0.000 description 2
102000004325 CX3C Chemokines Human genes 0.000 description 2
108010081635 CX3C Chemokines Proteins 0.000 description 2
108091008925 CX3C chemokine receptors Proteins 0.000 description 2
108091006146 Channels Proteins 0.000 description 2
241000557626 Corvus corax Species 0.000 description 2
108010036281 Cyclic Nucleotide-Gated Cation Channels Proteins 0.000 description 2
102000012003 Cyclic Nucleotide-Gated Cation Channels Human genes 0.000 description 2
IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 2
230000004568 DNA-binding Effects 0.000 description 2
BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
238000002965 ELISA Methods 0.000 description 2
102100027723 Endogenous retrovirus group K member 6 Rec protein Human genes 0.000 description 2
101710091045 Envelope protein Proteins 0.000 description 2
241000206602 Eukaryota Species 0.000 description 2
OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 2
108010008959 G-Protein-Coupled Receptor Kinases Proteins 0.000 description 2
102000006575 G-Protein-Coupled Receptor Kinases Human genes 0.000 description 2
241000713813 Gibbon ape leukemia virus Species 0.000 description 2
102000005720 Glutathione transferase Human genes 0.000 description 2
108010070675 Glutathione transferase Proteins 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
101710154606 Hemagglutinin Proteins 0.000 description 2
241000282412 Homo Species 0.000 description 2
102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 2
108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 2
229940122355 Insulin sensitizer Drugs 0.000 description 2
108091092195 Intron Proteins 0.000 description 2
108090000862 Ion Channels Proteins 0.000 description 2
102000004310 Ion Channels Human genes 0.000 description 2
108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 2
102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 2
LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 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
241000713666 Lentivirus Species 0.000 description 2
101710125418 Major capsid protein Proteins 0.000 description 2
108010052285 Membrane Proteins Proteins 0.000 description 2
102000018697 Membrane Proteins Human genes 0.000 description 2
241001529936 Murinae Species 0.000 description 2
241000714177 Murine leukemia virus Species 0.000 description 2
241000699660 Mus musculus Species 0.000 description 2
101000746021 Mus musculus CX3C chemokine receptor 1 Proteins 0.000 description 2
108091061960 Naked DNA Proteins 0.000 description 2
101710093908 Outer capsid protein VP4 Proteins 0.000 description 2
101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 2
108010067902 Peptide Library Proteins 0.000 description 2
108010081690 Pertussis Toxin Proteins 0.000 description 2
108010064785 Phospholipases Proteins 0.000 description 2
102000015439 Phospholipases Human genes 0.000 description 2
241000276498 Pollachius virens Species 0.000 description 2
ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
101710176177 Protein A56 Proteins 0.000 description 2
108090000315 Protein Kinase C Proteins 0.000 description 2
102000003923 Protein Kinase C Human genes 0.000 description 2
108010076504 Protein Sorting Signals Proteins 0.000 description 2
101710188315 Protein X Proteins 0.000 description 2
241000700157 Rattus norvegicus Species 0.000 description 2
101000854518 Rattus norvegicus Fractalkine Proteins 0.000 description 2
108020004511 Recombinant DNA Proteins 0.000 description 2
YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
240000004808 Saccharomyces cerevisiae Species 0.000 description 2
FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
238000002105 Southern blotting Methods 0.000 description 2
229940100389 Sulfonylurea Drugs 0.000 description 2
101710120037 Toxin CcdB Proteins 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
IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
108020005202 Viral DNA Proteins 0.000 description 2
239000002253 acid Substances 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000000853 adhesive Substances 0.000 description 2
230000001070 adhesive effect Effects 0.000 description 2
239000000443 aerosol Substances 0.000 description 2
230000032683 aging Effects 0.000 description 2
PMMURAAUARKVCB-UHFFFAOYSA-N alpha-D-ara-dHexp Natural products OCC1OC(O)CC(O)C1O PMMURAAUARKVCB-UHFFFAOYSA-N 0.000 description 2
230000004075 alteration Effects 0.000 description 2
230000033115 angiogenesis Effects 0.000 description 2
238000010171 animal model Methods 0.000 description 2
230000003178 anti-diabetic effect Effects 0.000 description 2
239000003472 antidiabetic agent Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
206010003246 arthritis Diseases 0.000 description 2
238000000376 autoradiography Methods 0.000 description 2
230000001580 bacterial effect Effects 0.000 description 2
210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 2
230000009286 beneficial effect Effects 0.000 description 2
229920001222 biopolymer Polymers 0.000 description 2
210000001185 bone marrow Anatomy 0.000 description 2
210000002798 bone marrow cell Anatomy 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
238000000423 cell based assay Methods 0.000 description 2
239000013592 cell lysate Substances 0.000 description 2
239000007795 chemical reaction product Substances 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
238000004590 computer program Methods 0.000 description 2
230000021615 conjugation Effects 0.000 description 2
238000010276 construction Methods 0.000 description 2
230000002596 correlated effect Effects 0.000 description 2
229940095074 cyclic amp Drugs 0.000 description 2
235000018417 cysteine Nutrition 0.000 description 2
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
210000000805 cytoplasm Anatomy 0.000 description 2
238000013500 data storage Methods 0.000 description 2
230000002950 deficient Effects 0.000 description 2
FMGSKLZLMKYGDP-USOAJAOKSA-N dehydroepiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 FMGSKLZLMKYGDP-USOAJAOKSA-N 0.000 description 2
239000003398 denaturant Substances 0.000 description 2
238000004925 denaturation Methods 0.000 description 2
230000036425 denaturation Effects 0.000 description 2
239000003599 detergent Substances 0.000 description 2
229950006137 dexfosfoserine Drugs 0.000 description 2
150000001982 diacylglycerols Chemical class 0.000 description 2
230000029087 digestion Effects 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
238000006073 displacement reaction Methods 0.000 description 2
239000000386 donor Substances 0.000 description 2
239000000975 dye Substances 0.000 description 2
210000002889 endothelial cell Anatomy 0.000 description 2
238000005516 engineering process Methods 0.000 description 2
230000002255 enzymatic effect Effects 0.000 description 2
201000010063 epididymitis Diseases 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000012530 fluid Substances 0.000 description 2
235000013305 food Nutrition 0.000 description 2
239000000499 gel Substances 0.000 description 2
238000007429 general method Methods 0.000 description 2
238000007446 glucose tolerance test Methods 0.000 description 2
ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 2
PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
239000008187 granular material Substances 0.000 description 2
229960000789 guanidine hydrochloride Drugs 0.000 description 2
PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 2
239000000185 hemagglutinin Substances 0.000 description 2
239000000833 heterodimer Substances 0.000 description 2
235000009200 high fat diet Nutrition 0.000 description 2
238000012203 high throughput assay Methods 0.000 description 2
238000013537 high throughput screening Methods 0.000 description 2
210000004295 hippocampal neuron Anatomy 0.000 description 2
210000005260 human cell Anatomy 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
230000003053 immunization Effects 0.000 description 2
238000002649 immunization Methods 0.000 description 2
230000000984 immunochemical effect Effects 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
229960000367 inositol Drugs 0.000 description 2
230000002427 irreversible effect Effects 0.000 description 2
238000002955 isolation Methods 0.000 description 2
150000002611 lead compounds Chemical class 0.000 description 2
210000004698 lymphocyte Anatomy 0.000 description 2
239000000463 material Substances 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
150000002739 metals Chemical class 0.000 description 2
XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 2
229960003105 metformin Drugs 0.000 description 2
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-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
239000000178 monomer Substances 0.000 description 2
230000035772 mutation Effects 0.000 description 2
210000000822 natural killer cell Anatomy 0.000 description 2
239000013642 negative control Substances 0.000 description 2
210000002569 neuron Anatomy 0.000 description 2
102000037979 non-receptor tyrosine kinases Human genes 0.000 description 2
108091008046 non-receptor tyrosine kinases Proteins 0.000 description 2
238000001216 nucleic acid method Methods 0.000 description 2
230000001575 pathological effect Effects 0.000 description 2
230000007170 pathology Effects 0.000 description 2
210000005259 peripheral blood Anatomy 0.000 description 2
239000011886 peripheral blood Substances 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
239000004417 polycarbonate Substances 0.000 description 2
239000011148 porous material Substances 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
230000008569 process Effects 0.000 description 2
230000017854 proteolysis Effects 0.000 description 2
230000009257 reactivity Effects 0.000 description 2
102000037983 regulatory factors Human genes 0.000 description 2
108091008025 regulatory factors Proteins 0.000 description 2
238000003571 reporter gene assay Methods 0.000 description 2
238000007894 restriction fragment length polymorphism technique Methods 0.000 description 2
206010039073 rheumatoid arthritis Diseases 0.000 description 2
238000011808 rodent model Methods 0.000 description 2
230000011664 signaling Effects 0.000 description 2
150000003384 small molecules Chemical class 0.000 description 2
229910001415 sodium ion Inorganic materials 0.000 description 2
238000002764 solid phase assay Methods 0.000 description 2
238000003746 solid phase reaction Methods 0.000 description 2
238000010671 solid-state reaction Methods 0.000 description 2
210000004989 spleen cell Anatomy 0.000 description 2
150000003431 steroids Chemical class 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
239000013589 supplement Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
210000005222 synovial tissue Anatomy 0.000 description 2
150000001467 thiazolidinediones Chemical class 0.000 description 2
238000013518 transcription Methods 0.000 description 2
230000035897 transcription Effects 0.000 description 2
230000002103 transcriptional effect Effects 0.000 description 2
230000009466 transformation Effects 0.000 description 2
230000032258 transport Effects 0.000 description 2
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
238000000108 ultra-filtration Methods 0.000 description 2
230000003827 upregulation Effects 0.000 description 2
238000010200 validation analysis Methods 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 1
BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 description 1
LLJFMFZYVVLQKT-UHFFFAOYSA-N 1-cyclohexyl-3-[4-[2-(7-methoxy-4,4-dimethyl-1,3-dioxo-2-isoquinolinyl)ethyl]phenyl]sulfonylurea Chemical compound C=1C(OC)=CC=C(C(C2=O)(C)C)C=1C(=O)N2CCC(C=C1)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 LLJFMFZYVVLQKT-UHFFFAOYSA-N 0.000 description 1
VGONTNSXDCQUGY-RRKCRQDMSA-N 2'-deoxyinosine Chemical group C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC2=O)=C2N=C1 VGONTNSXDCQUGY-RRKCRQDMSA-N 0.000 description 1
BHNQPLPANNDEGL-UHFFFAOYSA-N 2-(4-octylphenoxy)ethanol Chemical compound CCCCCCCCC1=CC=C(OCCO)C=C1 BHNQPLPANNDEGL-UHFFFAOYSA-N 0.000 description 1
KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 1
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
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
208000030507 AIDS Diseases 0.000 description 1
229920000936 Agarose Polymers 0.000 description 1
244000105975 Antidesma platyphyllum Species 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
108090001008 Avidin Proteins 0.000 description 1
210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
108010077805 Bacterial Proteins Proteins 0.000 description 1
229940123208 Biguanide Drugs 0.000 description 1
206010006187 Breast cancer Diseases 0.000 description 1
208000026310 Breast neoplasm Diseases 0.000 description 1
241000208199 Buxus sempervirens Species 0.000 description 1
102100031172 C-C chemokine receptor type 1 Human genes 0.000 description 1
101710149814 C-C chemokine receptor type 1 Proteins 0.000 description 1
102100036166 C-X-C chemokine receptor type 1 Human genes 0.000 description 1
101710082501 C-X-C chemokine receptor type 1 Proteins 0.000 description 1
108091008927 CC chemokine receptors Proteins 0.000 description 1
102000005674 CCR Receptors Human genes 0.000 description 1
210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
108050006947 CXC Chemokine Proteins 0.000 description 1
102000019388 CXC chemokine Human genes 0.000 description 1
108091008928 CXC chemokine receptors Proteins 0.000 description 1
102000054900 CXCR Receptors Human genes 0.000 description 1
102000000905 Cadherin Human genes 0.000 description 1
108050007957 Cadherin Proteins 0.000 description 1
108090000565 Capsid Proteins Proteins 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
102000053642 Catalytic RNA Human genes 0.000 description 1
108090000994 Catalytic RNA Proteins 0.000 description 1
102000001327 Chemokine CCL5 Human genes 0.000 description 1
108010055166 Chemokine CCL5 Proteins 0.000 description 1
108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 1
RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 1
VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
KPSRODZRAIWAKH-JTQLQIEISA-N Ciprofibrate Natural products C1=CC(OC(C)(C)C(O)=O)=CC=C1[C@H]1C(Cl)(Cl)C1 KPSRODZRAIWAKH-JTQLQIEISA-N 0.000 description 1
108700010070 Codon Usage Proteins 0.000 description 1
238000000018 DNA microarray Methods 0.000 description 1
239000003155 DNA primer Substances 0.000 description 1
238000001712 DNA sequencing Methods 0.000 description 1
241000450599 DNA viruses Species 0.000 description 1
FMGSKLZLMKYGDP-UHFFFAOYSA-N Dehydroepiandrosterone Natural products C1C(O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CC=C21 FMGSKLZLMKYGDP-UHFFFAOYSA-N 0.000 description 1
SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 1
108091027757 Deoxyribozyme Proteins 0.000 description 1
239000004338 Dichlorodifluoromethane Substances 0.000 description 1
108010016626 Dipeptides Proteins 0.000 description 1
102000015554 Dopamine receptor Human genes 0.000 description 1
108050004812 Dopamine receptor Proteins 0.000 description 1
108010065556 Drug Receptors Proteins 0.000 description 1
102000013138 Drug Receptors Human genes 0.000 description 1
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
238000012286 ELISA Assay Methods 0.000 description 1
206010048554 Endothelial dysfunction Diseases 0.000 description 1
101800001467 Envelope glycoprotein E2 Proteins 0.000 description 1
241000701959 Escherichia virus Lambda Species 0.000 description 1
208000010201 Exanthema Diseases 0.000 description 1
108700024394 Exon Proteins 0.000 description 1
241000724791 Filamentous phage Species 0.000 description 1
102100039556 Galectin-4 Human genes 0.000 description 1
HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
208000002705 Glucose Intolerance Diseases 0.000 description 1
108010027915 Glutamate Receptors Proteins 0.000 description 1
102000018899 Glutamate Receptors Human genes 0.000 description 1
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
108010093488 His-His-His-His-His-His Proteins 0.000 description 1
101000884714 Homo sapiens Beta-defensin 4A Proteins 0.000 description 1
101001048716 Homo sapiens ETS domain-containing protein Elk-4 Proteins 0.000 description 1
101000851181 Homo sapiens Epidermal growth factor receptor Proteins 0.000 description 1
101000608765 Homo sapiens Galectin-4 Proteins 0.000 description 1
101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
101000628949 Homo sapiens Mitogen-activated protein kinase 10 Proteins 0.000 description 1
101001109800 Homo sapiens Pro-neuregulin-1, membrane-bound isoform Proteins 0.000 description 1
101001092930 Homo sapiens Prosaposin Proteins 0.000 description 1
101000911753 Homo sapiens Protein FAM107B Proteins 0.000 description 1
101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 1
108010001336 Horseradish Peroxidase Proteins 0.000 description 1
241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
108010058683 Immobilized Proteins Proteins 0.000 description 1
108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
206010056997 Impaired fasting glucose Diseases 0.000 description 1
208000026350 Inborn Genetic disease Diseases 0.000 description 1
102000003746 Insulin Receptor Human genes 0.000 description 1
108010001127 Insulin Receptor Proteins 0.000 description 1
108090001007 Interleukin-8 Proteins 0.000 description 1
102000004890 Interleukin-8 Human genes 0.000 description 1
108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 1
102000019145 JUN kinase activity proteins Human genes 0.000 description 1
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-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
QEFRNWWLZKMPFJ-ZXPFJRLXSA-N L-methionine (R)-S-oxide Chemical compound C[S@@](=O)CC[C@H]([NH3+])C([O-])=O QEFRNWWLZKMPFJ-ZXPFJRLXSA-N 0.000 description 1
QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Natural products CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 description 1
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
108090001090 Lectins Proteins 0.000 description 1
102000004856 Lectins Human genes 0.000 description 1
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
108060001084 Luciferase Proteins 0.000 description 1
239000005089 Luciferase Substances 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 1
102100026931 Mitogen-activated protein kinase 10 Human genes 0.000 description 1
241000713869 Moloney murine leukemia virus Species 0.000 description 1
102000016943 Muramidase Human genes 0.000 description 1
108010014251 Muramidase Proteins 0.000 description 1
102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 1
108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 1
102000047918 Myelin Basic Human genes 0.000 description 1
101710107068 Myelin basic protein Proteins 0.000 description 1
108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
108700019961 Neoplasm Genes Proteins 0.000 description 1
102000048850 Neoplasm Genes Human genes 0.000 description 1
206010029350 Neurotoxicity Diseases 0.000 description 1
108090000590 Neurotransmitter Receptors Proteins 0.000 description 1
239000000020 Nitrocellulose Substances 0.000 description 1
108020004711 Nucleic Acid Probes Proteins 0.000 description 1
108020005187 Oligonucleotide Probes Proteins 0.000 description 1
108700020796 Oncogene Proteins 0.000 description 1
102000043276 Oncogene Human genes 0.000 description 1
206010033307 Overweight Diseases 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
108010028924 PPAR alpha Proteins 0.000 description 1
102000023984 PPAR alpha Human genes 0.000 description 1
108010016731 PPAR gamma Proteins 0.000 description 1
102000000536 PPAR gamma Human genes 0.000 description 1
108010044210 PPAR-beta Proteins 0.000 description 1
239000002033 PVDF binder Substances 0.000 description 1
241001494479 Pecora Species 0.000 description 1
102000057297 Pepsin A Human genes 0.000 description 1
108090000284 Pepsin A Proteins 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
108091093037 Peptide nucleic acid Proteins 0.000 description 1
108010043958 Peptoids Proteins 0.000 description 1
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
206010035226 Plasma cell myeloma Diseases 0.000 description 1
102100036154 Platelet basic protein Human genes 0.000 description 1
239000004952 Polyamide Substances 0.000 description 1
229920002873 Polyethylenimine Polymers 0.000 description 1
239000004642 Polyimide Substances 0.000 description 1
239000004743 Polypropylene Substances 0.000 description 1
239000004793 Polystyrene Substances 0.000 description 1
229920002396 Polyurea Polymers 0.000 description 1
241000288906 Primates Species 0.000 description 1
241001415846 Procellariidae Species 0.000 description 1
102100026983 Protein FAM107B Human genes 0.000 description 1
102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 1
108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 1
241000125945 Protoparvovirus Species 0.000 description 1
101710097451 Putative G-protein coupled receptor Proteins 0.000 description 1
102100039117 Putative vomeronasal receptor-like protein 4 Human genes 0.000 description 1
108010066717 Q beta Replicase Proteins 0.000 description 1
238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 1
102100039664 Receptor-type tyrosine-protein phosphatase H Human genes 0.000 description 1
241000219061 Rheum Species 0.000 description 1
108091028664 Ribonucleotide Proteins 0.000 description 1
241000283984 Rodentia Species 0.000 description 1
102000001332 SRC Human genes 0.000 description 1
108060006706 SRC Proteins 0.000 description 1
102000003800 Selectins Human genes 0.000 description 1
108090000184 Selectins Proteins 0.000 description 1
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
241000700584 Simplexvirus Species 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
101800001271 Surface protein Proteins 0.000 description 1
210000001744 T-lymphocyte Anatomy 0.000 description 1
108700012920 TNF Proteins 0.000 description 1
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
239000004473 Threonine Substances 0.000 description 1
AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
206010044221 Toxic encephalopathy Diseases 0.000 description 1
102000004338 Transferrin Human genes 0.000 description 1
108090000901 Transferrin Proteins 0.000 description 1
108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
102100040247 Tumor necrosis factor Human genes 0.000 description 1
206010054094 Tumour necrosis Diseases 0.000 description 1
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
241000251539 Vertebrata <Metazoa> Species 0.000 description 1
208000036142 Viral infection Diseases 0.000 description 1
108070000030 Viral receptors Proteins 0.000 description 1
229930003316 Vitamin D Natural products 0.000 description 1
QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 1
INAPMGSXUVUWAF-GCVPSNMTSA-N [(2r,3s,5r,6r)-2,3,4,5,6-pentahydroxycyclohexyl] dihydrogen phosphate Chemical compound OC1[C@H](O)[C@@H](O)C(OP(O)(O)=O)[C@H](O)[C@@H]1O INAPMGSXUVUWAF-GCVPSNMTSA-N 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
229960002632 acarbose Drugs 0.000 description 1
XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
230000001133 acceleration Effects 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
229960001466 acetohexamide Drugs 0.000 description 1
VGZSUPCWNCWDAN-UHFFFAOYSA-N acetohexamide Chemical compound C1=CC(C(=O)C)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 VGZSUPCWNCWDAN-UHFFFAOYSA-N 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
108091005764 adaptor proteins Proteins 0.000 description 1
102000035181 adaptor proteins Human genes 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
230000002411 adverse Effects 0.000 description 1
239000011543 agarose gel Substances 0.000 description 1
238000007818 agglutination assay Methods 0.000 description 1
239000003513 alkali Substances 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
210000004102 animal cell Anatomy 0.000 description 1
238000005571 anion exchange chromatography Methods 0.000 description 1
238000000137 annealing Methods 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
230000009830 antibody antigen interaction Effects 0.000 description 1
210000000612 antigen-presenting cell Anatomy 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
235000009582 asparagine Nutrition 0.000 description 1
229960001230 asparagine Drugs 0.000 description 1
235000003704 aspartic acid Nutrition 0.000 description 1
238000003149 assay kit Methods 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
210000003719 b-lymphocyte Anatomy 0.000 description 1
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
229960000516 bezafibrate Drugs 0.000 description 1
IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 1
150000004283 biguanides Chemical class 0.000 description 1
239000003012 bilayer membrane Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
229960000074 biopharmaceutical Drugs 0.000 description 1
238000001574 biopsy Methods 0.000 description 1
125000005340 bisphosphate group Chemical group 0.000 description 1
230000017531 blood circulation Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
210000004958 brain cell Anatomy 0.000 description 1
210000005013 brain tissue Anatomy 0.000 description 1
238000004364 calculation method Methods 0.000 description 1
235000019577 caloric intake Nutrition 0.000 description 1
101150039352 can gene Proteins 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
239000002775 capsule Substances 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
125000002091 cationic group Chemical group 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
239000006143 cell culture medium Substances 0.000 description 1
230000032823 cell division Effects 0.000 description 1
230000010261 cell growth Effects 0.000 description 1
210000002421 cell wall Anatomy 0.000 description 1
230000019522 cellular metabolic process Effects 0.000 description 1
230000005754 cellular signaling Effects 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
210000001638 cerebellum Anatomy 0.000 description 1
239000002738 chelating agent Substances 0.000 description 1
238000009614 chemical analysis method Methods 0.000 description 1
230000002925 chemical effect Effects 0.000 description 1
125000003636 chemical group Chemical group 0.000 description 1
238000006757 chemical reactions by type Methods 0.000 description 1
239000013626 chemical specie Substances 0.000 description 1
239000005081 chemiluminescent agent Substances 0.000 description 1
230000003399 chemotactic effect Effects 0.000 description 1
230000035605 chemotaxis Effects 0.000 description 1
210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
SIHHLZPXQLFPMC-UHFFFAOYSA-N chloroform;methanol;hydrate Chemical compound O.OC.ClC(Cl)Cl SIHHLZPXQLFPMC-UHFFFAOYSA-N 0.000 description 1
229960001761 chlorpropamide Drugs 0.000 description 1
235000012000 cholesterol Nutrition 0.000 description 1
208000037976 chronic inflammation Diseases 0.000 description 1
208000037893 chronic inflammatory disorder Diseases 0.000 description 1
YZFWTZACSRHJQD-UHFFFAOYSA-N ciglitazone Chemical compound C=1C=C(CC2C(NC(=O)S2)=O)C=CC=1OCC1(C)CCCCC1 YZFWTZACSRHJQD-UHFFFAOYSA-N 0.000 description 1
229950009226 ciglitazone Drugs 0.000 description 1
229960002174 ciprofibrate Drugs 0.000 description 1
KPSRODZRAIWAKH-UHFFFAOYSA-N ciprofibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1C1C(Cl)(Cl)C1 KPSRODZRAIWAKH-UHFFFAOYSA-N 0.000 description 1
208000035850 clinical syndrome Diseases 0.000 description 1
229960001214 clofibrate Drugs 0.000 description 1
KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 1
238000000975 co-precipitation Methods 0.000 description 1
238000012761 co-transfection Methods 0.000 description 1
OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
230000002860 competitive effect Effects 0.000 description 1
238000003271 compound fluorescence assay Methods 0.000 description 1
238000001218 confocal laser scanning microscopy Methods 0.000 description 1
108010035886 connective tissue-activating peptide Proteins 0.000 description 1
239000000470 constituent Substances 0.000 description 1
238000011109 contamination Methods 0.000 description 1
239000013068 control sample Substances 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
208000029078 coronary artery disease Diseases 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
238000004132 cross linking Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
229920005565 cyclic polymer Polymers 0.000 description 1
150000001945 cysteines Chemical group 0.000 description 1
102000003675 cytokine receptors Human genes 0.000 description 1
108010057085 cytokine receptors Proteins 0.000 description 1
210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
230000007547 defect Effects 0.000 description 1
230000007812 deficiency Effects 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
230000001934 delay Effects 0.000 description 1
239000000841 delta opiate receptor agonist Substances 0.000 description 1
239000005547 deoxyribonucleotide Substances 0.000 description 1
125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
238000000586 desensitisation Methods 0.000 description 1
230000000368 destabilizing effect Effects 0.000 description 1
238000011026 diafiltration Methods 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
230000000378 dietary effect Effects 0.000 description 1
230000004069 differentiation Effects 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 compound 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
208000035475 disorder Diseases 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
230000007783 downstream signaling Effects 0.000 description 1
229940000406 drug candidate Drugs 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
241001493065 dsRNA viruses Species 0.000 description 1
230000004064 dysfunction Effects 0.000 description 1
235000006694 eating habits Nutrition 0.000 description 1
230000002500 effect on skin Effects 0.000 description 1
238000000295 emission spectrum Methods 0.000 description 1
230000002121 endocytic effect Effects 0.000 description 1
239000006274 endogenous ligand Substances 0.000 description 1
230000008694 endothelial dysfunction Effects 0.000 description 1
238000012869 ethanol precipitation Methods 0.000 description 1
LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
201000005884 exanthem Diseases 0.000 description 1
231100000318 excitotoxic Toxicity 0.000 description 1
230000003492 excitotoxic effect Effects 0.000 description 1
230000028023 exocytosis Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
229960002297 fenofibrate Drugs 0.000 description 1
YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
210000002950 fibroblast Anatomy 0.000 description 1
238000001914 filtration Methods 0.000 description 1
MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
238000000799 fluorescence microscopy Methods 0.000 description 1
239000003269 fluorescent indicator Substances 0.000 description 1
230000037406 food intake Effects 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
235000021588 free fatty acids Nutrition 0.000 description 1
238000002825 functional assay Methods 0.000 description 1
229960003627 gemfibrozil Drugs 0.000 description 1
238000001476 gene delivery Methods 0.000 description 1
230000030279 gene silencing Effects 0.000 description 1
230000009368 gene silencing by RNA Effects 0.000 description 1
238000012226 gene silencing method Methods 0.000 description 1
230000007274 generation of a signal involved in cell-cell signaling Effects 0.000 description 1
208000016361 genetic disease Diseases 0.000 description 1
208000004104 gestational diabetes Diseases 0.000 description 1
229960004580 glibenclamide Drugs 0.000 description 1
229960000346 gliclazide Drugs 0.000 description 1
229960004346 glimepiride Drugs 0.000 description 1
WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
229960001381 glipizide Drugs 0.000 description 1
ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 1
229960003468 gliquidone Drugs 0.000 description 1
230000004153 glucose metabolism Effects 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
125000003827 glycol group Chemical group 0.000 description 1
230000013595 glycosylation Effects 0.000 description 1
238000006206 glycosylation reaction Methods 0.000 description 1
229940120105 glynase Drugs 0.000 description 1
239000010931 gold Substances 0.000 description 1
229910052737 gold Inorganic materials 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
210000003714 granulocyte Anatomy 0.000 description 1
239000005090 green fluorescent protein Substances 0.000 description 1
235000009424 haa Nutrition 0.000 description 1
230000002650 habitual effect Effects 0.000 description 1
230000036541 health Effects 0.000 description 1
210000002064 heart cell Anatomy 0.000 description 1
210000005003 heart tissue Anatomy 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
210000003958 hematopoietic stem cell Anatomy 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
210000001320 hippocampus Anatomy 0.000 description 1
230000013632 homeostatic process Effects 0.000 description 1
230000006801 homologous recombination Effects 0.000 description 1
238000002744 homologous recombination Methods 0.000 description 1
108091008039 hormone receptors Proteins 0.000 description 1
102000055650 human NRG1 Human genes 0.000 description 1
150000001469 hydantoins Chemical class 0.000 description 1
150000002431 hydrogen Chemical group 0.000 description 1
239000000852 hydrogen donor Substances 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
229960002591 hydroxyproline Drugs 0.000 description 1
201000001421 hyperglycemia Diseases 0.000 description 1
210000002865 immune cell Anatomy 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
238000003119 immunoblot Methods 0.000 description 1
238000003365 immunocytochemistry Methods 0.000 description 1
230000005847 immunogenicity Effects 0.000 description 1
229940072221 immunoglobulins Drugs 0.000 description 1
238000003364 immunohistochemistry Methods 0.000 description 1
238000010324 immunological assay Methods 0.000 description 1
230000001976 improved effect Effects 0.000 description 1
238000007901 in situ hybridization Methods 0.000 description 1
238000000099 in vitro assay Methods 0.000 description 1
238000005462 in vivo assay Methods 0.000 description 1
230000006698 induction Effects 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
230000004941 influx Effects 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
230000006362 insulin response pathway Effects 0.000 description 1
102000006495 integrins Human genes 0.000 description 1
108010044426 integrins Proteins 0.000 description 1
102000002467 interleukin receptors Human genes 0.000 description 1
108010093036 interleukin receptors Proteins 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
230000037041 intracellular level Effects 0.000 description 1
102000027411 intracellular receptors Human genes 0.000 description 1
108091008582 intracellular receptors Proteins 0.000 description 1
230000004068 intracellular signaling Effects 0.000 description 1
238000007917 intracranial administration Methods 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000004255 ion exchange chromatography Methods 0.000 description 1
210000004153 islets of langerhan Anatomy 0.000 description 1
229960000310 isoleucine Drugs 0.000 description 1
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
238000000021 kinase assay Methods 0.000 description 1
238000011005 laboratory method Methods 0.000 description 1
229920000126 latex Polymers 0.000 description 1
239000004816 latex Substances 0.000 description 1
239000002523 lectin Substances 0.000 description 1
230000037356 lipid metabolism Effects 0.000 description 1
239000013554 lipid monolayer Substances 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
210000005228 liver tissue Anatomy 0.000 description 1
230000007774 longterm Effects 0.000 description 1
239000012139 lysis buffer Substances 0.000 description 1
229960000274 lysozyme Drugs 0.000 description 1
235000010335 lysozyme Nutrition 0.000 description 1
239000004325 lysozyme Substances 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
ADKOXSOCTOWDOP-UHFFFAOYSA-L magnesium;aluminum;dihydroxide;trihydrate Chemical compound O.O.O.[OH-].[OH-].[Mg+2].[Al] ADKOXSOCTOWDOP-UHFFFAOYSA-L 0.000 description 1
239000003550 marker Substances 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
235000012054 meals Nutrition 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
102000006240 membrane receptors Human genes 0.000 description 1
108020004084 membrane receptors Proteins 0.000 description 1
208000030159 metabolic disease Diseases 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
LSDPWZHWYPCBBB-UHFFFAOYSA-O methylsulfide anion Chemical compound [SH2+]C LSDPWZHWYPCBBB-UHFFFAOYSA-O 0.000 description 1
230000000813 microbial effect Effects 0.000 description 1
238000000520 microinjection Methods 0.000 description 1
210000004925 microvascular endothelial cell Anatomy 0.000 description 1
229960001110 miglitol Drugs 0.000 description 1
230000005012 migration Effects 0.000 description 1
230000001617 migratory effect Effects 0.000 description 1
108091005601 modified peptides Proteins 0.000 description 1
230000010070 molecular adhesion Effects 0.000 description 1
230000004001 molecular interaction Effects 0.000 description 1
239000002062 molecular scaffold Substances 0.000 description 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
210000000214 mouth Anatomy 0.000 description 1
238000002887 multiple sequence alignment Methods 0.000 description 1
210000000663 muscle cell Anatomy 0.000 description 1
230000000869 mutational effect Effects 0.000 description 1
201000000050 myeloid neoplasm Diseases 0.000 description 1
229960000698 nateglinide Drugs 0.000 description 1
OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 1
230000007135 neurotoxicity Effects 0.000 description 1
231100000228 neurotoxicity Toxicity 0.000 description 1
239000002858 neurotransmitter agent Substances 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
108010087904 neutravidin Proteins 0.000 description 1
229920001220 nitrocellulos Polymers 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
239000012457 nonaqueous media Substances 0.000 description 1
238000010606 normalization Methods 0.000 description 1
230000005937 nuclear translocation Effects 0.000 description 1
238000007826 nucleic acid assay Methods 0.000 description 1
239000002853 nucleic acid probe Substances 0.000 description 1
229920002113 octoxynol Polymers 0.000 description 1
238000002966 oligonucleotide array Methods 0.000 description 1
239000002751 oligonucleotide probe Substances 0.000 description 1
229920001542 oligosaccharide Polymers 0.000 description 1
150000002482 oligosaccharides Chemical class 0.000 description 1
229940127240 opiate Drugs 0.000 description 1
238000007410 oral glucose tolerance test Methods 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
201000008482 osteoarthritis Diseases 0.000 description 1
238000004091 panning Methods 0.000 description 1
238000012402 patch clamp technique Methods 0.000 description 1
229940111202 pepsin Drugs 0.000 description 1
210000003200 peritoneal cavity Anatomy 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
230000037081 physical activity Effects 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
229960005095 pioglitazone Drugs 0.000 description 1
230000036470 plasma concentration Effects 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
229920002401 polyacrylamide Polymers 0.000 description 1
238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
229920002647 polyamide Polymers 0.000 description 1
229920000412 polyarylene Polymers 0.000 description 1
229920000515 polycarbonate Polymers 0.000 description 1
201000010065 polycystic ovary syndrome Diseases 0.000 description 1
229920000728 polyester Polymers 0.000 description 1
229920000570 polyether Polymers 0.000 description 1
230000003234 polygenic effect Effects 0.000 description 1
229920001721 polyimide Polymers 0.000 description 1
229920001155 polypropylene Polymers 0.000 description 1
229920001296 polysiloxane Polymers 0.000 description 1
229920002223 polystyrene Polymers 0.000 description 1
229920002635 polyurethane Polymers 0.000 description 1
239000004814 polyurethane Substances 0.000 description 1
229920002981 polyvinylidene fluoride Polymers 0.000 description 1
230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
229960003611 pramlintide Drugs 0.000 description 1
108010029667 pramlintide Proteins 0.000 description 1
NRKVKVQDUCJPIZ-MKAGXXMWSA-N pramlintide acetate Chemical compound C([C@@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCCCN)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 NRKVKVQDUCJPIZ-MKAGXXMWSA-N 0.000 description 1
229960002847 prasterone Drugs 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
201000009104 prediabetes syndrome Diseases 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000000770 proinflammatory effect Effects 0.000 description 1
210000001236 prokaryotic cell Anatomy 0.000 description 1
AAEVYOVXGOFMJO-UHFFFAOYSA-N prometryn Chemical compound CSC1=NC(NC(C)C)=NC(NC(C)C)=N1 AAEVYOVXGOFMJO-UHFFFAOYSA-N 0.000 description 1
230000000644 propagated effect Effects 0.000 description 1
239000001294 propane Substances 0.000 description 1
239000003380 propellant Substances 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
235000019833 protease Nutrition 0.000 description 1
238000001742 protein purification Methods 0.000 description 1
239000012460 protein solution Substances 0.000 description 1
230000006337 proteolytic cleavage Effects 0.000 description 1
150000003235 pyrrolidines Chemical class 0.000 description 1
238000011002 quantification Methods 0.000 description 1
230000005855 radiation Effects 0.000 description 1
206010037844 rash Diseases 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000010188 recombinant method Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000004153 renaturation Methods 0.000 description 1
229960002354 repaglinide Drugs 0.000 description 1
230000004043 responsiveness Effects 0.000 description 1
108091008146 restriction endonucleases Proteins 0.000 description 1
239000012465 retentate Substances 0.000 description 1
210000000880 retinal rod photoreceptor cell Anatomy 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
239000002336 ribonucleotide Substances 0.000 description 1
125000002652 ribonucleotide group Chemical group 0.000 description 1
108091092562 ribozyme Proteins 0.000 description 1
229960004586 rosiglitazone Drugs 0.000 description 1
238000003345 scintillation counting Methods 0.000 description 1
CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
230000000276 sedentary effect Effects 0.000 description 1
108020002447 serine esterase Proteins 0.000 description 1
102000005428 serine esterase Human genes 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
230000035939 shock Effects 0.000 description 1
239000013605 shuttle vector Substances 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
238000010532 solid phase synthesis reaction Methods 0.000 description 1
230000007928 solubilization Effects 0.000 description 1
238000005063 solubilization Methods 0.000 description 1
230000003381 solubilizing effect Effects 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000011301 standard therapy Methods 0.000 description 1
238000007619 statistical method Methods 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
210000001179 synovial fluid Anatomy 0.000 description 1
229920001059 synthetic polymer Polymers 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
238000002626 targeted therapy Methods 0.000 description 1
230000008685 targeting Effects 0.000 description 1
150000003505 terpenes Chemical class 0.000 description 1
MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 1
238000011285 therapeutic regimen Methods 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
150000003568 thioethers Chemical class 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
239000005495 thyroid hormone Substances 0.000 description 1
229940036555 thyroid hormone Drugs 0.000 description 1
230000001550 time effect Effects 0.000 description 1
229960002277 tolazamide Drugs 0.000 description 1
OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
229960005371 tolbutamide Drugs 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
239000003053 toxin Substances 0.000 description 1
231100000765 toxin Toxicity 0.000 description 1
108700012359 toxins Proteins 0.000 description 1
FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
239000012581 transferrin Substances 0.000 description 1
230000009261 transgenic effect Effects 0.000 description 1
238000011830 transgenic mouse model Methods 0.000 description 1
230000010474 transient expression Effects 0.000 description 1
230000001960 triggered effect Effects 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
229960001641 troglitazone Drugs 0.000 description 1
GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
230000010415 tropism Effects 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
239000004474 valine Substances 0.000 description 1
230000002792 vascular Effects 0.000 description 1
239000002435 venom Substances 0.000 description 1
231100000611 venom Toxicity 0.000 description 1
210000001048 venom Anatomy 0.000 description 1
230000009385 viral infection Effects 0.000 description 1
210000002845 virion Anatomy 0.000 description 1
239000000277 virosome Substances 0.000 description 1
235000019166 vitamin D Nutrition 0.000 description 1
239000011710 vitamin D Substances 0.000 description 1
150000003710 vitamin D derivatives Chemical class 0.000 description 1
229940046008 vitamin d Drugs 0.000 description 1
229960001729 voglibose Drugs 0.000 description 1
QDLHCMPXEPAAMD-QAIWCSMKSA-N wortmannin Chemical compound C1([C@]2(C)C3=C(C4=O)OC=C3C(=O)O[C@@H]2COC)=C4[C@@H]2CCC(=O)[C@@]2(C)C[C@H]1OC(C)=O QDLHCMPXEPAAMD-QAIWCSMKSA-N 0.000 description 1
QDLHCMPXEPAAMD-UHFFFAOYSA-N wortmannin Natural products COCC1OC(=O)C2=COC(C3=O)=C2C1(C)C1=C3C2CCC(=O)C2(C)CC1OC(C)=O QDLHCMPXEPAAMD-UHFFFAOYSA-N 0.000 description 1
238000001086 yeast two-hybrid system Methods 0.000 description 1
238000013293 zucker diabetic fatty rat Methods 0.000 description 1
238000011680 zucker rat Methods 0.000 description 1