SG185996A1 - Inhibitors of human phosphatidyl-inositol 3-kinase delta - Google Patents

Info

Publication number

SG185996A1

SG185996A1 SG2012083556A SG2012083556A SG185996A1 SG 185996 A1 SG185996 A1 SG 185996A1 SG 2012083556 A SG2012083556 A SG 2012083556A SG 2012083556 A SG2012083556 A SG 2012083556A SG 185996 A1 SG185996 A1 SG 185996A1

Authority

SG

Singapore

Prior art keywords

substituted

unsubstituted

compound

group

compounds

Prior art date

2007-11-13

Links

• Espacenet
• Global Dossier
• Discuss

• 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 title claims abstract description 105
• 108091007960 PI3Ks Proteins 0.000 title claims abstract description 80
• 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 title claims abstract description 30
• 239000003112 inhibitor Substances 0.000 title abstract description 80
• 150000001875 compounds Chemical class 0.000 claims abstract description 247
• 238000000034 method Methods 0.000 claims abstract description 128
• 230000000694 effects Effects 0.000 claims abstract description 122
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 63
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 38
• 208000035475 disorder Diseases 0.000 claims abstract description 36
• 210000000265 leukocyte Anatomy 0.000 claims abstract description 31
• 108091000080 Phosphotransferase Proteins 0.000 claims abstract description 7
• 102000020233 phosphotransferase Human genes 0.000 claims abstract description 7
• -1 Cs.gheterocycloalkyl Chemical group 0.000 claims description 49
• 125000003118 aryl group Chemical group 0.000 claims description 46
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 45
• 125000000217 alkyl group Chemical group 0.000 claims description 44
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 41
• 125000001072 heteroaryl group Chemical group 0.000 claims description 37
• 229920001184 polypeptide Polymers 0.000 claims description 36
• 125000001424 substituent group Chemical group 0.000 claims description 26
• 229910052739 hydrogen Inorganic materials 0.000 claims description 20
• 229910052757 nitrogen Inorganic materials 0.000 claims description 19
• 239000008194 pharmaceutical composition Substances 0.000 claims description 19
• 229910052760 oxygen Inorganic materials 0.000 claims description 18
• 150000003839 salts Chemical class 0.000 claims description 18
• 229910052720 vanadium Inorganic materials 0.000 claims description 18
• 125000005843 halogen group Chemical group 0.000 claims description 16
• 229910052717 sulfur Inorganic materials 0.000 claims description 16
• 229910052799 carbon Inorganic materials 0.000 claims description 12
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 11
• 208000032839 leukemia Diseases 0.000 claims description 9
• 125000005842 heteroatom Chemical group 0.000 claims description 8
• 125000002950 monocyclic group Chemical group 0.000 claims description 8
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
• 208000006673 asthma Diseases 0.000 claims description 7
• 125000004429 atom Chemical group 0.000 claims description 7
• 206010025323 Lymphomas Diseases 0.000 claims description 6
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
• 208000006386 Bone Resorption Diseases 0.000 claims description 5
• 125000002947 alkylene group Chemical group 0.000 claims description 5
• 125000005218 alkyleneheteroaryl group Chemical group 0.000 claims description 5
• 230000024279 bone resorption Effects 0.000 claims description 5
• 201000006417 multiple sclerosis Diseases 0.000 claims description 5
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
• 208000026278 immune system disease Diseases 0.000 claims description 3
• 206010025135 lupus erythematosus Diseases 0.000 claims description 3
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
• 201000009030 Carcinoma Diseases 0.000 claims description 2
• 206010020772 Hypertension Diseases 0.000 claims description 2
• 206010039491 Sarcoma Diseases 0.000 claims description 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
• XCUAIINAJCDIPM-XVFCMESISA-N N(4)-hydroxycytidine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=NO)C=C1 XCUAIINAJCDIPM-XVFCMESISA-N 0.000 claims 1
• VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical group OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 claims 1
• 108010029485 Protein Isoforms Proteins 0.000 abstract description 29
• 102000001708 Protein Isoforms Human genes 0.000 abstract description 29
• 201000010099 disease Diseases 0.000 abstract description 27
• 230000004054 inflammatory process Effects 0.000 abstract description 17
• 206010061218 Inflammation Diseases 0.000 abstract description 15
• 230000036039 immunity Effects 0.000 abstract description 2
• 210000004027 cell Anatomy 0.000 description 89
• 102000038030 PI3Ks Human genes 0.000 description 77
• 210000000440 neutrophil Anatomy 0.000 description 73
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 66
• 230000006870 function Effects 0.000 description 52
• 239000000243 solution Substances 0.000 description 45
• 239000000203 mixture Substances 0.000 description 35
• 210000003719 b-lymphocyte Anatomy 0.000 description 30
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
• 230000005764 inhibitory process Effects 0.000 description 27
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 26
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
• 102000004190 Enzymes Human genes 0.000 description 26
• 108090000790 Enzymes Proteins 0.000 description 26
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 26
• 238000012360 testing method Methods 0.000 description 25
• 206010028980 Neoplasm Diseases 0.000 description 24
• OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 24
• 239000000047 product Substances 0.000 description 24
• 238000011282 treatment Methods 0.000 description 22
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
• 239000003795 chemical substances by application Substances 0.000 description 21
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 20
• 102100026169 Phosphatidylinositol 3-kinase regulatory subunit alpha Human genes 0.000 description 20
• 210000001519 tissue Anatomy 0.000 description 20
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 19
• 230000001404 mediated effect Effects 0.000 description 19
• 210000002997 osteoclast Anatomy 0.000 description 19
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
• 238000003556 assay Methods 0.000 description 18
• 108090000623 proteins and genes Proteins 0.000 description 17
• 239000007787 solid Substances 0.000 description 16
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
• 230000004913 activation Effects 0.000 description 14
• 210000003651 basophil Anatomy 0.000 description 14
• 230000005012 migration Effects 0.000 description 14
• 238000013508 migration Methods 0.000 description 14
• 230000004044 response Effects 0.000 description 14
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
• 229940124639 Selective inhibitor Drugs 0.000 description 13
• 210000001744 T-lymphocyte Anatomy 0.000 description 13
• 201000011510 cancer Diseases 0.000 description 13
• 238000006243 chemical reaction Methods 0.000 description 13
• 238000009472 formulation Methods 0.000 description 13
• 230000035755 proliferation Effects 0.000 description 13
• 102000004169 proteins and genes Human genes 0.000 description 13
• 239000011541 reaction mixture Substances 0.000 description 13
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 12
• 108010008211 N-Formylmethionine Leucyl-Phenylalanine Proteins 0.000 description 12
• PRQROPMIIGLWRP-BZSNNMDCSA-N chemotactic peptide Chemical compound CSCC[C@H](NC=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 PRQROPMIIGLWRP-BZSNNMDCSA-N 0.000 description 12
• 239000000460 chlorine Substances 0.000 description 12
• 230000003389 potentiating effect Effects 0.000 description 12
• 238000000746 purification Methods 0.000 description 12
• 241001465754 Metazoa Species 0.000 description 11
• 238000010256 biochemical assay Methods 0.000 description 11
• 125000004122 cyclic group Chemical group 0.000 description 11
• 230000028023 exocytosis Effects 0.000 description 11
• 208000027866 inflammatory disease Diseases 0.000 description 11
• 208000028867 ischemia Diseases 0.000 description 11
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 11
• 238000002360 preparation method Methods 0.000 description 11
• 239000000651 prodrug Substances 0.000 description 11
• 229940002612 prodrug Drugs 0.000 description 11
• 230000001105 regulatory effect Effects 0.000 description 11
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 10
• CZQHHVNHHHRRDU-UHFFFAOYSA-N LY294002 Chemical compound C1=CC=C2C(=O)C=C(N3CCOCC3)OC2=C1C1=CC=CC=C1 CZQHHVNHHHRRDU-UHFFFAOYSA-N 0.000 description 10
• 241000124008 Mammalia Species 0.000 description 10
• KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 10
• 230000003197 catalytic effect Effects 0.000 description 10
• 229960001340 histamine Drugs 0.000 description 10
• 238000002390 rotary evaporation Methods 0.000 description 10
• 239000000126 substance Substances 0.000 description 10
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
• 230000006378 damage Effects 0.000 description 9
• 238000010790 dilution Methods 0.000 description 9
• 239000012895 dilution Substances 0.000 description 9
• 239000012634 fragment Substances 0.000 description 9
• 238000004128 high performance liquid chromatography Methods 0.000 description 9
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
• 238000000338 in vitro Methods 0.000 description 9
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
• 235000019341 magnesium sulphate Nutrition 0.000 description 9
• 238000003375 selectivity assay Methods 0.000 description 9
• 238000003756 stirring Methods 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• 239000013598 vector Substances 0.000 description 9
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
• 241000894006 Bacteria Species 0.000 description 8
• 102000016387 Pancreatic elastase Human genes 0.000 description 8
• 108010067372 Pancreatic elastase Proteins 0.000 description 8
• 206010063837 Reperfusion injury Diseases 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• 125000003342 alkenyl group Chemical group 0.000 description 8
• 230000001580 bacterial effect Effects 0.000 description 8
• 239000011575 calcium Substances 0.000 description 8
• 239000003814 drug Substances 0.000 description 8
• 238000013537 high throughput screening Methods 0.000 description 8
• 230000002757 inflammatory effect Effects 0.000 description 8
• 208000014674 injury Diseases 0.000 description 8
• 230000002147 killing effect Effects 0.000 description 8
• 238000007911 parenteral administration Methods 0.000 description 8
• 239000011780 sodium chloride Substances 0.000 description 8
• 208000011580 syndromic disease Diseases 0.000 description 8
• 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 8
• 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 8
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
• 239000012981 Hank's balanced salt solution Substances 0.000 description 7
• 125000000304 alkynyl group Chemical group 0.000 description 7
• 239000000427 antigen Substances 0.000 description 7
• 102000036639 antigens Human genes 0.000 description 7
• 108091007433 antigens Proteins 0.000 description 7
• 230000027455 binding Effects 0.000 description 7
• 230000015572 biosynthetic process Effects 0.000 description 7
• 210000004369 blood Anatomy 0.000 description 7
• 239000008280 blood Substances 0.000 description 7
• 238000005516 engineering process Methods 0.000 description 7
• 210000003630 histaminocyte Anatomy 0.000 description 7
• 150000002430 hydrocarbons Chemical group 0.000 description 7
• 238000001727 in vivo Methods 0.000 description 7
• 239000002502 liposome Substances 0.000 description 7
• 210000004698 lymphocyte Anatomy 0.000 description 7
• 239000002609 medium Substances 0.000 description 7
• 150000003905 phosphatidylinositols Chemical class 0.000 description 7
• 239000000758 substrate Substances 0.000 description 7
• 241000701447 unidentified baculovirus Species 0.000 description 7
• 229930024421 Adenine Natural products 0.000 description 6
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 6
• 101000873927 Homo sapiens Squamous cell carcinoma antigen recognized by T-cells 3 Proteins 0.000 description 6
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 6
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• 229960000643 adenine Drugs 0.000 description 6
• 125000002619 bicyclic group Chemical group 0.000 description 6
• 239000000872 buffer Substances 0.000 description 6
• 230000004663 cell proliferation Effects 0.000 description 6
• 238000012512 characterization method Methods 0.000 description 6
• 230000003399 chemotactic effect Effects 0.000 description 6
• 229940125904 compound 1 Drugs 0.000 description 6
• 239000012043 crude product Substances 0.000 description 6
• 239000003937 drug carrier Substances 0.000 description 6
• 239000000284 extract Substances 0.000 description 6
• 230000012010 growth Effects 0.000 description 6
• 230000016784 immunoglobulin production Effects 0.000 description 6
• 208000015181 infectious disease Diseases 0.000 description 6
• 150000002632 lipids Chemical class 0.000 description 6
• 238000004519 manufacturing process Methods 0.000 description 6
• 238000005259 measurement Methods 0.000 description 6
• 210000000056 organ Anatomy 0.000 description 6
• 239000012044 organic layer Substances 0.000 description 6
• 238000012552 review Methods 0.000 description 6
• 229920006395 saturated elastomer Polymers 0.000 description 6
• 239000003381 stabilizer Substances 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
• 230000001225 therapeutic effect Effects 0.000 description 6
• 238000012384 transportation and delivery Methods 0.000 description 6
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 6
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 5
• 241000283707 Capra Species 0.000 description 5
• 101001024630 Drosophila melanogaster RNA cytidine acetyltransferase Proteins 0.000 description 5
• 101000652705 Drosophila melanogaster Transcription initiation factor TFIID subunit 4 Proteins 0.000 description 5
• 108010010803 Gelatin Proteins 0.000 description 5
• 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 5
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 5
• 102000000588 Interleukin-2 Human genes 0.000 description 5
• 108010002350 Interleukin-2 Proteins 0.000 description 5
• 108010044467 Isoenzymes Proteins 0.000 description 5
• 241000699666 Mus <mouse, genus> Species 0.000 description 5
• 108091034117 Oligonucleotide Proteins 0.000 description 5
• 239000012828 PI3K inhibitor Substances 0.000 description 5
• UBXIJOJXUFYNRG-RJKBCLGNSA-N PIP[3'](17:0/20:4(5Z,8Z,11Z,14Z)) Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)O[C@H](COC(=O)CCCCCCCCCCCCCCCC)COP(O)(=O)O[C@H]1C(O)C(O)C(O)[C@@H](OP(O)(O)=O)C1O UBXIJOJXUFYNRG-RJKBCLGNSA-N 0.000 description 5
• 206010057249 Phagocytosis Diseases 0.000 description 5
• 101000996915 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Nucleoporin NSP1 Proteins 0.000 description 5
• 102100035748 Squamous cell carcinoma antigen recognized by T-cells 3 Human genes 0.000 description 5
• 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 5
• 208000027418 Wounds and injury Diseases 0.000 description 5
• 239000013543 active substance Substances 0.000 description 5
• 230000001154 acute effect Effects 0.000 description 5
• 230000008901 benefit Effects 0.000 description 5
• 210000000988 bone and bone Anatomy 0.000 description 5
• 229940098773 bovine serum albumin Drugs 0.000 description 5
• 210000004556 brain Anatomy 0.000 description 5
• 239000000969 carrier Substances 0.000 description 5
• 150000001768 cations Chemical class 0.000 description 5
• 238000000423 cell based assay Methods 0.000 description 5
• 230000001684 chronic effect Effects 0.000 description 5
• 231100000673 dose–response relationship Toxicity 0.000 description 5
• 229940079593 drug Drugs 0.000 description 5
• 239000012091 fetal bovine serum Substances 0.000 description 5
• 239000008273 gelatin Substances 0.000 description 5
• 229920000159 gelatin Polymers 0.000 description 5
• 235000019322 gelatine Nutrition 0.000 description 5
• 235000011852 gelatine desserts Nutrition 0.000 description 5
• 230000003993 interaction Effects 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• 229960001428 mercaptopurine Drugs 0.000 description 5
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
• 230000004048 modification Effects 0.000 description 5
• 238000012986 modification Methods 0.000 description 5
• 229930014626 natural product Natural products 0.000 description 5
• 230000008782 phagocytosis Effects 0.000 description 5
• 239000002953 phosphate buffered saline Substances 0.000 description 5
• 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 description 5
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• 239000002244 precipitate Substances 0.000 description 5
• 230000008569 process Effects 0.000 description 5
• 210000002966 serum Anatomy 0.000 description 5
• 239000007858 starting material Substances 0.000 description 5
• 230000000451 tissue damage Effects 0.000 description 5
• 231100000827 tissue damage Toxicity 0.000 description 5
• 231100000419 toxicity Toxicity 0.000 description 5
• 230000001988 toxicity Effects 0.000 description 5
• 238000005406 washing Methods 0.000 description 5
• DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 4
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• 125000004648 C2-C8 alkenyl group Chemical group 0.000 description 4
• 125000004649 C2-C8 alkynyl group Chemical group 0.000 description 4
• 125000000041 C6-C10 aryl group Chemical group 0.000 description 4
• 102000004127 Cytokines Human genes 0.000 description 4
• 108090000695 Cytokines Proteins 0.000 description 4
• 208000009329 Graft vs Host Disease Diseases 0.000 description 4
• 101150101095 Mmp12 gene Proteins 0.000 description 4
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• 206010040047 Sepsis Diseases 0.000 description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
• 238000002835 absorbance Methods 0.000 description 4
• 125000002252 acyl group Chemical group 0.000 description 4
• 125000004442 acylamino group Chemical group 0.000 description 4
• 125000004183 alkoxy alkyl group Chemical group 0.000 description 4
• 125000003545 alkoxy group Chemical group 0.000 description 4
• 125000004414 alkyl thio group Chemical group 0.000 description 4
• 238000010171 animal model Methods 0.000 description 4
• 230000004071 biological effect Effects 0.000 description 4
• 230000036983 biotransformation Effects 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 125000004432 carbon atom Chemical group C* 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 238000010367 cloning Methods 0.000 description 4
• 238000007796 conventional method Methods 0.000 description 4
• 125000004093 cyano group Chemical group *C#N 0.000 description 4
• 238000011161 development Methods 0.000 description 4
• 230000018109 developmental process Effects 0.000 description 4
• 239000008298 dragée Substances 0.000 description 4
• 229910052731 fluorine Inorganic materials 0.000 description 4
• 208000024908 graft versus host disease Diseases 0.000 description 4
• 210000003714 granulocyte Anatomy 0.000 description 4
• 125000001188 haloalkyl group Chemical group 0.000 description 4
• 239000004615 ingredient Substances 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• 239000010410 layer Substances 0.000 description 4
• 210000002540 macrophage Anatomy 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 4
• 239000001301 oxygen Chemical group 0.000 description 4
• 230000002093 peripheral effect Effects 0.000 description 4
• 150000003916 phosphatidylinositol 3,4,5-trisphosphates Chemical class 0.000 description 4
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
• 238000010992 reflux Methods 0.000 description 4
• 238000013207 serial dilution Methods 0.000 description 4
• 230000011664 signaling Effects 0.000 description 4
• 235000017557 sodium bicarbonate Nutrition 0.000 description 4
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
• 230000035886 specific defense system Effects 0.000 description 4
• 208000024891 symptom Diseases 0.000 description 4
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 3
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 3
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• GGHDCDOWCZZNNC-UHFFFAOYSA-N 2-(1-chloroethyl)-3-phenylpyrido[3,2-d]pyrimidin-4-one Chemical compound CC(Cl)C1=NC2=CC=CN=C2C(=O)N1C1=CC=CC=C1 GGHDCDOWCZZNNC-UHFFFAOYSA-N 0.000 description 3
• NCQAKQIBPIHJAX-UHFFFAOYSA-N 6-(chloromethyl)-3-methyl-5-phenyl-[1,2]oxazolo[5,4-d]pyrimidin-4-one Chemical compound O=C1C=2C(C)=NOC=2N=C(CCl)N1C1=CC=CC=C1 NCQAKQIBPIHJAX-UHFFFAOYSA-N 0.000 description 3
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
• 229920000936 Agarose Polymers 0.000 description 3
• 208000023275 Autoimmune disease Diseases 0.000 description 3
• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 description 3
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 3
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
• 206010014561 Emphysema Diseases 0.000 description 3
• 229920001917 Ficoll Polymers 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
• 206010020751 Hypersensitivity Diseases 0.000 description 3
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
• 241001529936 Murinae Species 0.000 description 3
• 239000002033 PVDF binder Substances 0.000 description 3
• 239000002202 Polyethylene glycol Substances 0.000 description 3
• 102000003923 Protein Kinase C Human genes 0.000 description 3
• 108090000315 Protein Kinase C Proteins 0.000 description 3
• 206010037660 Pyrexia Diseases 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• 102000014128 RANK Ligand Human genes 0.000 description 3
• 108010025832 RANK Ligand Proteins 0.000 description 3
• 206010040070 Septic Shock Diseases 0.000 description 3
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
• 208000006011 Stroke Diseases 0.000 description 3
• 206010052779 Transplant rejections Diseases 0.000 description 3
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
• 102100040247 Tumor necrosis factor Human genes 0.000 description 3
• 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 3
• 230000002159 abnormal effect Effects 0.000 description 3
• 239000012190 activator Substances 0.000 description 3
• 125000004644 alkyl sulfinyl group Chemical group 0.000 description 3
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
• 125000005275 alkylenearyl group Chemical group 0.000 description 3
• 208000026935 allergic disease Diseases 0.000 description 3
• 239000002585 base Substances 0.000 description 3
• 239000011324 bead Substances 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
• 230000003915 cell function Effects 0.000 description 3
• 229910052801 chlorine Inorganic materials 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 238000000576 coating method Methods 0.000 description 3
• 239000002299 complementary DNA Substances 0.000 description 3
• 229940125797 compound 12 Drugs 0.000 description 3
• 229940125782 compound 2 Drugs 0.000 description 3
• 229940125898 compound 5 Drugs 0.000 description 3
• 230000007423 decrease Effects 0.000 description 3
• 238000013461 design Methods 0.000 description 3
• VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 3
• 210000002889 endothelial cell Anatomy 0.000 description 3
• 210000003038 endothelium Anatomy 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 239000000499 gel Substances 0.000 description 3
• 125000004404 heteroalkyl group Chemical group 0.000 description 3
• 239000001257 hydrogen Substances 0.000 description 3
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 3
• 230000028993 immune response Effects 0.000 description 3
• 210000000987 immune system Anatomy 0.000 description 3
• 238000011534 incubation Methods 0.000 description 3
• 230000006698 induction Effects 0.000 description 3
• 210000004969 inflammatory cell Anatomy 0.000 description 3
• 238000001990 intravenous administration Methods 0.000 description 3
• 238000002955 isolation Methods 0.000 description 3
• 239000011777 magnesium Substances 0.000 description 3
• 229910052749 magnesium Inorganic materials 0.000 description 3
• 244000005700 microbiome Species 0.000 description 3
• 208000010125 myocardial infarction Diseases 0.000 description 3
• HHQJWDKIRXRTLS-UHFFFAOYSA-N n'-bromobutanediamide Chemical compound NC(=O)CCC(=O)NBr HHQJWDKIRXRTLS-UHFFFAOYSA-N 0.000 description 3
• 229910052759 nickel Inorganic materials 0.000 description 3
• 230000035781 nonspecific defense system Effects 0.000 description 3
• 239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 description 3
• 239000013612 plasmid Substances 0.000 description 3
• 229920001223 polyethylene glycol Polymers 0.000 description 3
• 108091033319 polynucleotide Proteins 0.000 description 3
• 102000040430 polynucleotide Human genes 0.000 description 3
• 239000002157 polynucleotide Substances 0.000 description 3
• 229920002981 polyvinylidene fluoride Polymers 0.000 description 3
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
• 229910000160 potassium phosphate Inorganic materials 0.000 description 3
• 235000011009 potassium phosphates Nutrition 0.000 description 3
• GUUBJKMBDULZTE-UHFFFAOYSA-M potassium;2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid;hydroxide Chemical compound [OH-].[K+].OCCN1CCN(CCS(O)(=O)=O)CC1 GUUBJKMBDULZTE-UHFFFAOYSA-M 0.000 description 3
• 230000002685 pulmonary effect Effects 0.000 description 3
• 239000012264 purified product Substances 0.000 description 3
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
• 230000002829 reductive effect Effects 0.000 description 3
• 230000010410 reperfusion Effects 0.000 description 3
• 238000012216 screening Methods 0.000 description 3
• 208000017520 skin disease Diseases 0.000 description 3
• 239000011734 sodium Substances 0.000 description 3
• 239000012453 solvate Substances 0.000 description 3
• 239000002904 solvent Substances 0.000 description 3
• 239000000600 sorbitol Substances 0.000 description 3
• 239000006228 supernatant Substances 0.000 description 3
• 230000002195 synergetic effect Effects 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• 238000004809 thin layer chromatography Methods 0.000 description 3
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
• 230000008733 trauma Effects 0.000 description 3
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
• ZGMNAIODRDOMEK-UHFFFAOYSA-N 1,1,1-trimethoxypropane Chemical compound CCC(OC)(OC)OC ZGMNAIODRDOMEK-UHFFFAOYSA-N 0.000 description 2
• LOZWAPSEEHRYPG-UHFFFAOYSA-N 1,4-dithiane Chemical compound C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 2
• XMTDEXIBNUMBAK-UHFFFAOYSA-N 1-methyl-5-nitro-n-phenylpyrazole-4-carboxamide Chemical compound CN1N=CC(C(=O)NC=2C=CC=CC=2)=C1[N+]([O-])=O XMTDEXIBNUMBAK-UHFFFAOYSA-N 0.000 description 2
• YTYVPZSRZWASHJ-UHFFFAOYSA-N 2-(1-aminoethyl)-3-phenylpyrido[3,2-d]pyrimidin-4-one Chemical compound CC(N)C1=NC2=CC=CN=C2C(=O)N1C1=CC=CC=C1 YTYVPZSRZWASHJ-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
• FBBIJRUGCXQPEQ-UHFFFAOYSA-N 3-(2-chloropropanoylamino)-n-phenylpyridine-2-carboxamide Chemical compound CC(Cl)C(=O)NC1=CC=CN=C1C(=O)NC1=CC=CC=C1 FBBIJRUGCXQPEQ-UHFFFAOYSA-N 0.000 description 2
• IGGZBKPYCZZSPA-UHFFFAOYSA-N 3-amino-n-phenylpyridine-2-carboxamide Chemical compound NC1=CC=CN=C1C(=O)NC1=CC=CC=C1 IGGZBKPYCZZSPA-UHFFFAOYSA-N 0.000 description 2
• BKTSOLRYTODUFR-UHFFFAOYSA-N 3-bromo-6-(1-bromoethyl)-1-methyl-5-phenylpyrazolo[3,4-d]pyrimidin-4-one Chemical compound CC(Br)C1=NC=2N(C)N=C(Br)C=2C(=O)N1C1=CC=CC=C1 BKTSOLRYTODUFR-UHFFFAOYSA-N 0.000 description 2
• WGDCOWOOGIGJDV-UHFFFAOYSA-N 5-amino-1-methyl-n-phenylpyrazole-4-carboxamide Chemical compound CN1N=CC(C(=O)NC=2C=CC=CC=2)=C1N WGDCOWOOGIGJDV-UHFFFAOYSA-N 0.000 description 2
• KBIDJVBQDUKSSC-UHFFFAOYSA-N 5-amino-3-methyl-n-phenyl-1,2-oxazole-4-carboxamide Chemical compound CC1=NOC(N)=C1C(=O)NC1=CC=CC=C1 KBIDJVBQDUKSSC-UHFFFAOYSA-N 0.000 description 2
• CPQLXZTVSCHWPG-UHFFFAOYSA-N 6-[1-(6-aminopurin-9-yl)ethyl]-3-bromo-1-methyl-5-phenylpyrazolo[3,4-d]pyrimidin-4-one Chemical compound C1=NC2=C(N)N=CN=C2N1C(C)C1=NC=2N(C)N=C(Br)C=2C(=O)N1C1=CC=CC=C1 CPQLXZTVSCHWPG-UHFFFAOYSA-N 0.000 description 2
• CTGFGRDVWBZYNB-UHFFFAOYSA-N 6-bromo-7h-purine Chemical compound BrC1=NC=NC2=C1NC=N2 CTGFGRDVWBZYNB-UHFFFAOYSA-N 0.000 description 2
• 244000215068 Acacia senegal Species 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• 229920001817 Agar Polymers 0.000 description 2
• 241000416162 Astragalus gummifer Species 0.000 description 2
• 201000001320 Atherosclerosis Diseases 0.000 description 2
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
• 241000283690 Bos taurus Species 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
• 108091007958 Class I PI3Ks Proteins 0.000 description 2
• 206010009900 Colitis ulcerative Diseases 0.000 description 2
• 206010010744 Conjunctivitis allergic Diseases 0.000 description 2
• 208000011231 Crohn disease Diseases 0.000 description 2
• 102000018832 Cytochromes Human genes 0.000 description 2
• 108010052832 Cytochromes Proteins 0.000 description 2
• 102000005768 DNA-Activated Protein Kinase Human genes 0.000 description 2
• 108010006124 DNA-Activated Protein Kinase Proteins 0.000 description 2
• 201000004624 Dermatitis Diseases 0.000 description 2
• 206010012438 Dermatitis atopic Diseases 0.000 description 2
• 206010012442 Dermatitis contact Diseases 0.000 description 2
• 206010051392 Diapedesis Diseases 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 238000002965 ELISA Methods 0.000 description 2
• 241000196324 Embryophyta Species 0.000 description 2
• 241000283074 Equus asinus Species 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• 206010018367 Glomerulonephritis chronic Diseases 0.000 description 2
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
• 229920000084 Gum arabic Polymers 0.000 description 2
• 239000007821 HATU Substances 0.000 description 2
• 239000007995 HEPES buffer Substances 0.000 description 2
• WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
• 208000030836 Hashimoto thyroiditis Diseases 0.000 description 2
• 208000010496 Heart Arrest Diseases 0.000 description 2
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
• 241000238631 Hexapoda Species 0.000 description 2
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
• 201000009906 Meningitis Diseases 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• 208000034578 Multiple myelomas Diseases 0.000 description 2
• 208000000112 Myalgia Diseases 0.000 description 2
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
• 206010051606 Necrotising colitis Diseases 0.000 description 2
• 108010038807 Oligopeptides Proteins 0.000 description 2
• 102000015636 Oligopeptides Human genes 0.000 description 2
• 108700020796 Oncogene Proteins 0.000 description 2
• 102000004264 Osteopontin Human genes 0.000 description 2
• 108010081689 Osteopontin Proteins 0.000 description 2
• 101150037263 PIP2 gene Proteins 0.000 description 2
• WSLBJQQQZZTFBA-MLUQOLBVSA-N PIP[4'](17:0/20:4(5Z,8Z,11Z,14Z)) Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)O[C@H](COC(=O)CCCCCCCCCCCCCCCC)COP(O)(=O)OC1C(O)C(O)C(OP(O)(O)=O)[C@@H](O)C1O WSLBJQQQZZTFBA-MLUQOLBVSA-N 0.000 description 2
• 108091005804 Peptidases Proteins 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 239000004743 Polypropylene Substances 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• 241000288906 Primates Species 0.000 description 2
• 239000004365 Protease Substances 0.000 description 2
• 102000001253 Protein Kinase Human genes 0.000 description 2
• 201000004681 Psoriasis Diseases 0.000 description 2
• 239000012980 RPMI-1640 medium Substances 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• 108020004511 Recombinant DNA Proteins 0.000 description 2
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
• 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 2
• 101100262439 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) UBA2 gene Proteins 0.000 description 2
• 102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• 241000191967 Staphylococcus aureus Species 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• 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 2
• 229930006000 Sucrose Natural products 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 102000019197 Superoxide Dismutase Human genes 0.000 description 2
• 108010012715 Superoxide dismutase Proteins 0.000 description 2
• GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
• 229920001615 Tragacanth Polymers 0.000 description 2
• 201000006704 Ulcerative Colitis Diseases 0.000 description 2
• 208000024780 Urticaria Diseases 0.000 description 2
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
• 235000010489 acacia gum Nutrition 0.000 description 2
• 239000000205 acacia gum Substances 0.000 description 2
• 238000009825 accumulation Methods 0.000 description 2
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 235000010419 agar Nutrition 0.000 description 2
• 239000000556 agonist Substances 0.000 description 2
• 235000010443 alginic acid Nutrition 0.000 description 2
• 229920000615 alginic acid Polymers 0.000 description 2
• 125000003282 alkyl amino group Chemical group 0.000 description 2
• 150000001350 alkyl halides Chemical class 0.000 description 2
• 208000002205 allergic conjunctivitis Diseases 0.000 description 2
• 230000007815 allergy Effects 0.000 description 2
• 230000003281 allosteric effect Effects 0.000 description 2
• 150000001412 amines Chemical class 0.000 description 2
• 229940024606 amino acid Drugs 0.000 description 2
• 150000001413 amino acids Chemical class 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 230000002917 arthritic effect Effects 0.000 description 2
• 206010003246 arthritis Diseases 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• 201000008937 atopic dermatitis Diseases 0.000 description 2
• 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 2
• 239000011230 binding agent Substances 0.000 description 2
• 230000008499 blood brain barrier function Effects 0.000 description 2
• 230000017531 blood circulation Effects 0.000 description 2
• 210000001218 blood-brain barrier Anatomy 0.000 description 2
• 210000001185 bone marrow Anatomy 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 150000001649 bromium compounds Chemical class 0.000 description 2
• 239000007853 buffer solution Substances 0.000 description 2
• 239000007975 buffered saline Substances 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 230000020411 cell activation Effects 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 230000036755 cellular response Effects 0.000 description 2
• 239000001913 cellulose Substances 0.000 description 2
• 235000010980 cellulose Nutrition 0.000 description 2
• 210000003169 central nervous system Anatomy 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• 230000035605 chemotaxis Effects 0.000 description 2
• 238000002512 chemotherapy Methods 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 239000000470 constituent Substances 0.000 description 2
• 208000010247 contact dermatitis Diseases 0.000 description 2
• 239000013058 crude material Substances 0.000 description 2
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
• 230000001086 cytosolic effect Effects 0.000 description 2
• 210000004268 dentin Anatomy 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 239000008121 dextrose Substances 0.000 description 2
• 206010012601 diabetes mellitus Diseases 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 230000008030 elimination Effects 0.000 description 2
• 238000003379 elimination reaction Methods 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 239000002158 endotoxin Substances 0.000 description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 239000010685 fatty oil Substances 0.000 description 2
• 238000000855 fermentation Methods 0.000 description 2
• 230000004151 fermentation Effects 0.000 description 2
• 239000000706 filtrate Substances 0.000 description 2
• 239000012467 final product Substances 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 125000001153 fluoro group Chemical group F* 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 239000011521 glass Substances 0.000 description 2
• RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
• 230000003394 haemopoietic effect Effects 0.000 description 2
• 210000002216 heart Anatomy 0.000 description 2
• 210000003958 hematopoietic stem cell Anatomy 0.000 description 2
• 229960002897 heparin Drugs 0.000 description 2
• 229920000669 heparin Polymers 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 125000002883 imidazolyl group Chemical group 0.000 description 2
• 238000011065 in-situ storage Methods 0.000 description 2
• 230000004941 influx Effects 0.000 description 2
• 238000001802 infusion Methods 0.000 description 2
• 239000000543 intermediate Substances 0.000 description 2
• 238000007912 intraperitoneal administration Methods 0.000 description 2
• 150000004694 iodide salts Chemical class 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• 239000011630 iodine Substances 0.000 description 2
• 229920006008 lipopolysaccharide Polymers 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 210000004072 lung Anatomy 0.000 description 2
• 210000003563 lymphoid tissue Anatomy 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• 239000003550 marker Substances 0.000 description 2
• 239000011159 matrix material Substances 0.000 description 2
• 229960004452 methionine Drugs 0.000 description 2
• 238000010369 molecular cloning Methods 0.000 description 2
• 208000037890 multiple organ injury Diseases 0.000 description 2
• 208000031225 myocardial ischemia Diseases 0.000 description 2
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
• 210000004897 n-terminal region Anatomy 0.000 description 2
• 125000001624 naphthyl group Chemical group 0.000 description 2
• 208000004995 necrotizing enterocolitis Diseases 0.000 description 2
• 210000000944 nerve tissue Anatomy 0.000 description 2
• 230000011242 neutrophil chemotaxis Effects 0.000 description 2
• 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 150000002894 organic compounds Chemical class 0.000 description 2
• 230000003204 osmotic effect Effects 0.000 description 2
• 125000004043 oxo group Chemical group O=* 0.000 description 2
• 201000006195 perinatal necrotizing enterocolitis Diseases 0.000 description 2
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 150000003904 phospholipids Chemical class 0.000 description 2
• 229920000728 polyester Polymers 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• 229920001155 polypropylene Polymers 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 235000011056 potassium acetate Nutrition 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
• 238000012545 processing Methods 0.000 description 2
• 230000002062 proliferating effect Effects 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 125000006239 protecting group Chemical group 0.000 description 2
• 108060006633 protein kinase Proteins 0.000 description 2
• 125000003373 pyrazinyl group Chemical group 0.000 description 2
• 230000005855 radiation Effects 0.000 description 2
• 238000010188 recombinant method Methods 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 230000028327 secretion Effects 0.000 description 2
• 208000013223 septicemia Diseases 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
• 230000009870 specific binding Effects 0.000 description 2
• 210000000952 spleen Anatomy 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 230000000638 stimulation Effects 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 235000000346 sugar Nutrition 0.000 description 2
• 125000004434 sulfur atom Chemical group 0.000 description 2
• 230000001629 suppression Effects 0.000 description 2
• 239000004094 surface-active agent Substances 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 238000013268 sustained release Methods 0.000 description 2
• 239000012730 sustained-release form Substances 0.000 description 2
• 230000008961 swelling Effects 0.000 description 2
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
• 229940124597 therapeutic agent Drugs 0.000 description 2
• 231100001274 therapeutic index Toxicity 0.000 description 2
• 229940104230 thymidine Drugs 0.000 description 2
• 208000037816 tissue injury Diseases 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• 230000001052 transient effect Effects 0.000 description 2
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
• 230000002792 vascular Effects 0.000 description 2
• 239000011534 wash buffer Substances 0.000 description 2
• 239000011701 zinc Substances 0.000 description 2
• LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
• JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
• JEQDSBVHLKBEIZ-REOHCLBHSA-N (2s)-2-chloropropanoyl chloride Chemical compound C[C@H](Cl)C(Cl)=O JEQDSBVHLKBEIZ-REOHCLBHSA-N 0.000 description 1
• 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
• 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 description 1
• WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
• VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical class CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
• VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical class CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• XLSBYMROSSRRAV-UHFFFAOYSA-N 1-methyl-5-nitropyrazole-4-carboxylic acid Chemical compound CN1N=CC(C(O)=O)=C1[N+]([O-])=O XLSBYMROSSRRAV-UHFFFAOYSA-N 0.000 description 1
• 125000005955 1H-indazolyl group Chemical group 0.000 description 1
• APXRHPDHORGIEB-UHFFFAOYSA-N 1H-pyrazolo[4,3-d]pyrimidine Chemical class N1=CN=C2C=NNC2=C1 APXRHPDHORGIEB-UHFFFAOYSA-N 0.000 description 1
• 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
• WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical class BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
• RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
• MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
• BOOMHTFCWOJWFO-UHFFFAOYSA-N 3-aminopyridine-2-carboxylic acid Chemical compound NC1=CC=CN=C1C(O)=O BOOMHTFCWOJWFO-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• MCGBIXXDQFWVDW-UHFFFAOYSA-N 4,5-dihydro-1h-pyrazole Chemical compound C1CC=NN1 MCGBIXXDQFWVDW-UHFFFAOYSA-N 0.000 description 1
• MRUWJENAYHTDQG-UHFFFAOYSA-N 4H-pyran Chemical compound C1C=COC=C1 MRUWJENAYHTDQG-UHFFFAOYSA-N 0.000 description 1
• YAHRYQHRXYOHCK-UHFFFAOYSA-N 6-[(6-aminopurin-6-yl)methyl]-3-methyl-5-phenyl-[1,2]oxazolo[5,4-d]pyrimidin-4-one Chemical compound O=C1C=2C(C)=NOC=2N=C(CC2(N)C3=NC=NC3=NC=N2)N1C1=CC=CC=C1 YAHRYQHRXYOHCK-UHFFFAOYSA-N 0.000 description 1
• KFDRJNHQMCJYCJ-UHFFFAOYSA-N 6-ethyl-1-methyl-5-phenylpyrazolo[3,4-d]pyrimidin-4-one Chemical compound CCC1=NC=2N(C)N=CC=2C(=O)N1C1=CC=CC=C1 KFDRJNHQMCJYCJ-UHFFFAOYSA-N 0.000 description 1
• 229950006316 6-mercaptopurine monohydrate Drugs 0.000 description 1
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
• 241000251468 Actinopterygii Species 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• 206010001889 Alveolitis Diseases 0.000 description 1
• 206010003267 Arthritis reactive Diseases 0.000 description 1
• 206010003594 Ataxia telangiectasia Diseases 0.000 description 1
• 241000271566 Aves Species 0.000 description 1
• 201000001178 Bacterial Pneumonia Diseases 0.000 description 1
• 208000027496 Behcet disease Diseases 0.000 description 1
• 208000009137 Behcet syndrome Diseases 0.000 description 1
• DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
• 206010005003 Bladder cancer Diseases 0.000 description 1
• 208000003174 Brain Neoplasms Diseases 0.000 description 1
• 206010006458 Bronchitis chronic Diseases 0.000 description 1
• 208000011691 Burkitt lymphomas Diseases 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• 241000700198 Cavia Species 0.000 description 1
• 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
• 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
• 208000025985 Central nervous system inflammatory disease Diseases 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 102000041075 Class I family Human genes 0.000 description 1
• 108091060777 Class I family Proteins 0.000 description 1
• 108091007959 Class II PI3Ks Proteins 0.000 description 1
• 108091007963 Class III PI3Ks Proteins 0.000 description 1
• 101100382092 Clostridium botulinum D phage ntnha gene Proteins 0.000 description 1
• 101100004794 Clostridium botulinum ant gene Proteins 0.000 description 1
• 101100007328 Cocos nucifera COS-1 gene Proteins 0.000 description 1
• 102000008186 Collagen Human genes 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• 241000938605 Crocodylia Species 0.000 description 1
• 201000003883 Cystic fibrosis Diseases 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
• 108020004414 DNA Proteins 0.000 description 1
• 208000006313 Delayed Hypersensitivity Diseases 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical group O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 206010014824 Endotoxic shock Diseases 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 241000206602 Eukaryota Species 0.000 description 1
• 108091006020 Fc-tagged proteins Proteins 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 206010016654 Fibrosis Diseases 0.000 description 1
• 102000011652 Formyl peptide receptors Human genes 0.000 description 1
• 108010076288 Formyl peptide receptors Proteins 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
• 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
• IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
• 241000206672 Gelidium Species 0.000 description 1
• 206010018366 Glomerulonephritis acute Diseases 0.000 description 1
• SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
• 108010024636 Glutathione Proteins 0.000 description 1
• 201000005569 Gout Diseases 0.000 description 1
• 206010018634 Gouty Arthritis Diseases 0.000 description 1
• 208000003084 Graves Ophthalmopathy Diseases 0.000 description 1
• 102000009465 Growth Factor Receptors Human genes 0.000 description 1
• 108010009202 Growth Factor Receptors Proteins 0.000 description 1
• 206010019196 Head injury Diseases 0.000 description 1
• 208000032843 Hemorrhage Diseases 0.000 description 1
• 208000032456 Hemorrhagic Shock Diseases 0.000 description 1
• 206010019728 Hepatitis alcoholic Diseases 0.000 description 1
• 108010068250 Herpes Simplex Virus Protein Vmw65 Proteins 0.000 description 1
• 101000605630 Homo sapiens Phosphatidylinositol 3-kinase catalytic subunit type 3 Proteins 0.000 description 1
• 101000582929 Homo sapiens Plasmolipin Proteins 0.000 description 1
• 101001059443 Homo sapiens Serine/threonine-protein kinase MARK1 Proteins 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 206010021138 Hypovolaemic shock Diseases 0.000 description 1
• 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 1
• 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
• 206010023330 Keloid scar Diseases 0.000 description 1
• FFEARJCKVFRZRR-UHFFFAOYSA-N L-Methionine Natural products CSCCC(N)C(O)=O FFEARJCKVFRZRR-UHFFFAOYSA-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
• 229930195722 L-methionine Natural products 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 206010069698 Langerhans' cell histiocytosis Diseases 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 208000019693 Lung disease Diseases 0.000 description 1
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
• 108090000988 Lysostaphin Proteins 0.000 description 1
• 102000043129 MHC class I family Human genes 0.000 description 1
• 108091054437 MHC class I family Proteins 0.000 description 1
• 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
• 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
• 206010064912 Malignant transformation Diseases 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 241000252067 Megalops atlanticus Species 0.000 description 1
• 206010027476 Metastases Diseases 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical class COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
• BAVYZALUXZFZLV-UHFFFAOYSA-O Methylammonium ion Chemical compound [NH3+]C BAVYZALUXZFZLV-UHFFFAOYSA-O 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
• 108091028043 Nucleic acid sequence Proteins 0.000 description 1
• 206010030113 Oedema Diseases 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 240000007594 Oryza sativa Species 0.000 description 1
• 235000007164 Oryza sativa Nutrition 0.000 description 1
• 208000010191 Osteitis Deformans Diseases 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 229940116355 PI3 kinase inhibitor Drugs 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 208000027868 Paget disease Diseases 0.000 description 1
• 208000002193 Pain Diseases 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 102000035195 Peptidases Human genes 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
• 102100038329 Phosphatidylinositol 3-kinase catalytic subunit type 3 Human genes 0.000 description 1
• 206010035226 Plasma cell myeloma Diseases 0.000 description 1
• 102100030265 Plasmolipin Human genes 0.000 description 1
• 102000010995 Pleckstrin homology domains Human genes 0.000 description 1
• 108050001185 Pleckstrin homology domains Proteins 0.000 description 1
• 206010035664 Pneumonia Diseases 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
• 239000012979 RPMI medium Substances 0.000 description 1
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
• 206010039085 Rhinitis allergic Diseases 0.000 description 1
• 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
• 108010031271 Saccharomyces cerevisiae Proteins Proteins 0.000 description 1
• 206010053879 Sepsis syndrome Diseases 0.000 description 1
• 206010049771 Shock haemorrhagic Diseases 0.000 description 1
• 201000010001 Silicosis Diseases 0.000 description 1
• 208000021386 Sjogren Syndrome Diseases 0.000 description 1
• 244000061456 Solanum tuberosum Species 0.000 description 1
• 235000002595 Solanum tuberosum Nutrition 0.000 description 1
• 208000005392 Spasm Diseases 0.000 description 1
• 201000002661 Spondylitis Diseases 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 241000282898 Sus scrofa Species 0.000 description 1
• 206010042674 Swelling Diseases 0.000 description 1
• 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 description 1
• 230000006044 T cell activation Effects 0.000 description 1
• 230000006052 T cell proliferation Effects 0.000 description 1
• 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 1
• 101150106148 TOR1 gene Proteins 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
• 208000007536 Thrombosis Diseases 0.000 description 1
• IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Natural products O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
• 206010044248 Toxic shock syndrome Diseases 0.000 description 1
• 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
• 235000021307 Triticum Nutrition 0.000 description 1
• 244000098338 Triticum aestivum Species 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• GBOGMAARMMDZGR-UHFFFAOYSA-N UNPD149280 Natural products N1C(=O)C23OC(=O)C=CC(O)CCCC(C)CC=CC3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 GBOGMAARMMDZGR-UHFFFAOYSA-N 0.000 description 1
• 206010046851 Uveitis Diseases 0.000 description 1
• 206010047115 Vasculitis Diseases 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• 230000001594 aberrant effect Effects 0.000 description 1
• 229940022663 acetate Drugs 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 239000011149 active material Substances 0.000 description 1
• 231100000851 acute glomerulonephritis Toxicity 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 208000002353 alcoholic hepatitis Diseases 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• 208000037884 allergic airway inflammation Diseases 0.000 description 1
• 230000000172 allergic effect Effects 0.000 description 1
• 201000010105 allergic rhinitis Diseases 0.000 description 1
• AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
• AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 230000003321 amplification Effects 0.000 description 1
• 208000007502 anemia Diseases 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 230000000259 anti-tumor effect Effects 0.000 description 1
• 239000002246 antineoplastic agent Substances 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 208000024998 atopic conjunctivitis Diseases 0.000 description 1
• 208000010668 atopic eczema Diseases 0.000 description 1
• 230000006472 autoimmune response Effects 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 239000000440 bentonite Substances 0.000 description 1
• 229910000278 bentonite Inorganic materials 0.000 description 1
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
• 229940077388 benzenesulfonate Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 229940050390 benzoate Drugs 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
• 210000000941 bile Anatomy 0.000 description 1
• 230000008827 biological function Effects 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 239000011616 biotin Substances 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 201000001531 bladder carcinoma Diseases 0.000 description 1
• 230000000903 blocking effect Effects 0.000 description 1
• 230000036770 blood supply Effects 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 210000001124 body fluid Anatomy 0.000 description 1
• 239000010839 body fluid Substances 0.000 description 1
• 210000002798 bone marrow cell Anatomy 0.000 description 1
• 208000029028 brain injury Diseases 0.000 description 1
• 210000005013 brain tissue Anatomy 0.000 description 1
• 201000009267 bronchiectasis Diseases 0.000 description 1
• 206010006451 bronchitis Diseases 0.000 description 1
• 235000010633 broth Nutrition 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• 229910002091 carbon monoxide Inorganic materials 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 210000000845 cartilage Anatomy 0.000 description 1
• 230000021164 cell adhesion Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 230000022534 cell killing Effects 0.000 description 1
• 210000002421 cell wall Anatomy 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 230000033077 cellular process Effects 0.000 description 1
• 230000005754 cellular signaling Effects 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 229920006184 cellulose methylcellulose Polymers 0.000 description 1
• 230000002490 cerebral effect Effects 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 239000012829 chemotherapy agent Substances 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 125000000068 chlorophenyl group Chemical group 0.000 description 1
• 208000007451 chronic bronchitis Diseases 0.000 description 1
• 208000037976 chronic inflammation Diseases 0.000 description 1
• 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
• 230000004087 circulation Effects 0.000 description 1
• 229940001468 citrate Drugs 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 230000000052 comparative effect Effects 0.000 description 1
• 238000004624 confocal microscopy Methods 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 210000004351 coronary vessel Anatomy 0.000 description 1
• 230000004940 costimulation Effects 0.000 description 1
• 230000000139 costimulatory effect Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 125000000392 cycloalkenyl group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
• GBOGMAARMMDZGR-TYHYBEHESA-N cytochalasin B Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@@H]3/C=C/C[C@H](C)CCC[C@@H](O)/C=C/C(=O)O[C@@]23C(=O)N1)=C)C)C1=CC=CC=C1 GBOGMAARMMDZGR-TYHYBEHESA-N 0.000 description 1
• GBOGMAARMMDZGR-JREHFAHYSA-N cytochalasin B Natural products C[C@H]1CCC[C@@H](O)C=CC(=O)O[C@@]23[C@H](C=CC1)[C@H](O)C(=C)[C@@H](C)[C@@H]2[C@H](Cc4ccccc4)NC3=O GBOGMAARMMDZGR-JREHFAHYSA-N 0.000 description 1
• 230000009089 cytolysis Effects 0.000 description 1
• 231100000433 cytotoxic Toxicity 0.000 description 1
• 229940127089 cytotoxic agent Drugs 0.000 description 1
• 230000001472 cytotoxic effect Effects 0.000 description 1
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 210000004443 dendritic cell Anatomy 0.000 description 1
• 230000001066 destructive effect Effects 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 150000008050 dialkyl sulfates Chemical class 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-O diethylammonium Chemical compound CC[NH2+]CC HPNMFZURTQLUMO-UHFFFAOYSA-O 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• SPCNPOWOBZQWJK-UHFFFAOYSA-N dimethoxy-(2-propan-2-ylsulfanylethylsulfanyl)-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)SCCSC(C)C SPCNPOWOBZQWJK-UHFFFAOYSA-N 0.000 description 1
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
• GAFRWLVTHPVQGK-UHFFFAOYSA-N dipentyl sulfate Chemical class CCCCCOS(=O)(=O)OCCCCC GAFRWLVTHPVQGK-UHFFFAOYSA-N 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• 230000008034 disappearance Effects 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 239000012153 distilled water Substances 0.000 description 1
• 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 239000012154 double-distilled water Substances 0.000 description 1
• 239000000890 drug combination Substances 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 238000007877 drug screening Methods 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• 230000001210 effect on neutrophils Effects 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 206010014599 encephalitis Diseases 0.000 description 1
• 210000003989 endothelium vascular Anatomy 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 210000003979 eosinophil Anatomy 0.000 description 1
• 208000003401 eosinophilic granuloma Diseases 0.000 description 1
• 210000003743 erythrocyte Anatomy 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• 229940011871 estrogen Drugs 0.000 description 1
• 239000000262 estrogen Substances 0.000 description 1
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• QUSNBJAOOMFDIB-UHFFFAOYSA-O ethylaminium Chemical compound CC[NH3+] QUSNBJAOOMFDIB-UHFFFAOYSA-O 0.000 description 1
• 230000005713 exacerbation Effects 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000013604 expression vector Substances 0.000 description 1
• 210000003414 extremity Anatomy 0.000 description 1
• 201000001155 extrinsic allergic alveolitis Diseases 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 230000027950 fever generation Effects 0.000 description 1
• 239000000835 fiber Substances 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• 230000004761 fibrosis Effects 0.000 description 1
• 239000012997 ficoll-paque Substances 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000003818 flash chromatography Methods 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 238000002376 fluorescence recovery after photobleaching Methods 0.000 description 1
• 125000001207 fluorophenyl group Chemical group 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 239000012737 fresh medium Substances 0.000 description 1
• ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 108020001507 fusion proteins Proteins 0.000 description 1
• 102000037865 fusion proteins Human genes 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 229940097043 glucuronic acid Drugs 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 229960003180 glutathione Drugs 0.000 description 1
• 210000000224 granular leucocyte Anatomy 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 238000000227 grinding Methods 0.000 description 1
• 208000035474 group of disease Diseases 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 125000005347 halocycloalkyl group Chemical group 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 210000005003 heart tissue Anatomy 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 201000005787 hematologic cancer Diseases 0.000 description 1
• 230000002489 hematologic effect Effects 0.000 description 1
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
• MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
• 239000000833 heterodimer Substances 0.000 description 1
• 102000034345 heterotrimeric G proteins Human genes 0.000 description 1
• 108091006093 heterotrimeric G proteins Proteins 0.000 description 1
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 102000053508 human MARK1 Human genes 0.000 description 1
• 210000005260 human cell Anatomy 0.000 description 1
• 229940106780 human fibrinogen Drugs 0.000 description 1
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
• 208000022098 hypersensitivity pneumonitis Diseases 0.000 description 1
• 230000008105 immune reaction Effects 0.000 description 1
• 230000006054 immunological memory Effects 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 238000005462 in vivo assay Methods 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 239000000411 inducer Substances 0.000 description 1
• 230000007574 infarction Effects 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 230000000266 injurious effect Effects 0.000 description 1
• CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical group O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
• 238000003780 insertion Methods 0.000 description 1
• 230000037431 insertion Effects 0.000 description 1
• 230000004073 interleukin-2 production Effects 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 208000001286 intracranial vasospasm Diseases 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000007914 intraventricular administration Methods 0.000 description 1
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
• 125000005956 isoquinolyl group Chemical group 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 208000011379 keloid formation Diseases 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 210000003292 kidney cell Anatomy 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 239000004922 lacquer Substances 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 210000001821 langerhans cell Anatomy 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 231100000518 lethal Toxicity 0.000 description 1
• 230000001665 lethal effect Effects 0.000 description 1
• 206010024378 leukocytosis Diseases 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 125000005647 linker group Chemical group 0.000 description 1
• 229940057995 liquid paraffin Drugs 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 230000000527 lymphocytic effect Effects 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 230000036212 malign transformation Effects 0.000 description 1
• 230000036210 malignancy Effects 0.000 description 1
• 210000004962 mammalian cell Anatomy 0.000 description 1
• 208000027202 mammary Paget disease Diseases 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• MIKKOBKEXMRYFQ-WZTVWXICSA-N meglumine amidotrizoate Chemical compound C[NH2+]C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I MIKKOBKEXMRYFQ-WZTVWXICSA-N 0.000 description 1
• 238000002074 melt spinning Methods 0.000 description 1
• WFFQYWAAEWLHJC-UHFFFAOYSA-N mercaptopurine hydrate Chemical compound O.S=C1NC=NC2=C1NC=N2 WFFQYWAAEWLHJC-UHFFFAOYSA-N 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 230000009401 metastasis Effects 0.000 description 1
• 125000005395 methacrylic acid group Chemical group 0.000 description 1
• 229930182817 methionine Natural products 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 238000010232 migration assay Methods 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 238000000329 molecular dynamics simulation Methods 0.000 description 1
• 239000003068 molecular probe Substances 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 210000001616 monocyte Anatomy 0.000 description 1
• 230000035772 mutation Effects 0.000 description 1
• 201000000050 myeloid neoplasm Diseases 0.000 description 1
• 210000004165 myocardium Anatomy 0.000 description 1
• 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
• 230000001613 neoplastic effect Effects 0.000 description 1
• 230000003961 neuronal insult Effects 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
• 125000006501 nitrophenyl group Chemical group 0.000 description 1
• 239000002736 nonionic surfactant Substances 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 231100000956 nontoxicity Toxicity 0.000 description 1
• 238000003199 nucleic acid amplification method Methods 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 102000027450 oncoproteins Human genes 0.000 description 1
• 108091008819 oncoproteins Proteins 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 239000003791 organic solvent mixture Substances 0.000 description 1
• 201000008482 osteoarthritis Diseases 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• 230000000242 pagocytic effect Effects 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 244000052769 pathogen Species 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 239000000816 peptidomimetic Substances 0.000 description 1
• 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
• 210000001428 peripheral nervous system Anatomy 0.000 description 1
• 150000002978 peroxides Chemical class 0.000 description 1
• JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 150000008105 phosphatidylcholines Chemical class 0.000 description 1
• RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
• 150000003906 phosphoinositides Chemical class 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 229940075930 picrate Drugs 0.000 description 1
• OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 229950010765 pivalate Drugs 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
• 238000007747 plating Methods 0.000 description 1
• 208000008423 pleurisy Diseases 0.000 description 1
• 229920002401 polyacrylamide Polymers 0.000 description 1
• 125000003367 polycyclic group Chemical group 0.000 description 1
• 229930001119 polyketide Natural products 0.000 description 1
• 125000000830 polyketide group Chemical group 0.000 description 1
• 229930001118 polyketide hybrid Natural products 0.000 description 1
• 125000003308 polyketide hybrid group Chemical group 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 229920000136 polysorbate Polymers 0.000 description 1
• 239000013641 positive control Substances 0.000 description 1
• 230000026341 positive regulation of angiogenesis Effects 0.000 description 1
• 239000008057 potassium phosphate buffer Substances 0.000 description 1
• 238000011533 pre-incubation Methods 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 230000009696 proliferative response Effects 0.000 description 1
• 229940127293 prostanoid Drugs 0.000 description 1
• 150000003814 prostanoids Chemical class 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical group N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
• 201000003651 pulmonary sarcoidosis Diseases 0.000 description 1
• 238000004080 punching Methods 0.000 description 1
• IGFXRKMLLMBKSA-UHFFFAOYSA-N purine Chemical compound N1=C[N]C2=NC=NC2=C1 IGFXRKMLLMBKSA-UHFFFAOYSA-N 0.000 description 1
• USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
• 150000004944 pyrrolopyrimidines Chemical class 0.000 description 1
• 125000001453 quaternary ammonium group Chemical group 0.000 description 1
• 238000010791 quenching Methods 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 102000016914 ras Proteins Human genes 0.000 description 1
• 108010014186 ras Proteins Proteins 0.000 description 1
• 208000002574 reactive arthritis Diseases 0.000 description 1
• 239000003642 reactive oxygen metabolite Substances 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 210000002345 respiratory system Anatomy 0.000 description 1
• 208000023504 respiratory system disease Diseases 0.000 description 1
• 230000004043 responsiveness Effects 0.000 description 1
• 230000003307 reticuloendothelial effect Effects 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 235000009566 rice Nutrition 0.000 description 1
• 238000005096 rolling process Methods 0.000 description 1
• 239000000523 sample Substances 0.000 description 1
• 231100000241 scar Toxicity 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 230000036303 septic shock Effects 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 206010040560 shock Diseases 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 239000012439 solid excipient Substances 0.000 description 1
• 238000005063 solubilization Methods 0.000 description 1
• 230000007928 solubilization Effects 0.000 description 1
• 238000000527 sonication Methods 0.000 description 1
• 208000020431 spinal cord injury Diseases 0.000 description 1
• 210000004988 splenocyte Anatomy 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 238000001694 spray drying Methods 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 230000000707 stereoselective effect Effects 0.000 description 1
• 230000004960 subcellular localization Effects 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 239000011593 sulfur Chemical group 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 238000012385 systemic delivery Methods 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 206010043554 thrombocytopenia Diseases 0.000 description 1
• 230000009772 tissue formation Effects 0.000 description 1
• 239000004408 titanium dioxide Substances 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 125000003944 tolyl group Chemical group 0.000 description 1
• 101150049389 tor2 gene Proteins 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 231100000816 toxic dose Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• 230000000472 traumatic effect Effects 0.000 description 1
• 150000003626 triacylglycerols Chemical class 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
• 239000006150 trypticase soy agar Substances 0.000 description 1
• 230000004614 tumor growth Effects 0.000 description 1
• 208000027930 type IV hypersensitivity disease Diseases 0.000 description 1
• 238000005199 ultracentrifugation Methods 0.000 description 1
• 210000003606 umbilical vein Anatomy 0.000 description 1
• ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
• 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
• 210000002700 urine Anatomy 0.000 description 1
• 230000007054 vacuolar protein processing Effects 0.000 description 1
• 230000032665 vasculature development Effects 0.000 description 1
• 230000002227 vasoactive effect Effects 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 201000005539 vernal conjunctivitis Diseases 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1