ES2698950T3 - Anticuerpos capaces de unirse al Factor XI de coagulación y/o a su forma activada, Factor XIa, y usos de los mismos - Google Patents

Info

Publication number

ES2698950T3

ES2698950T3 ES13721746T ES13721746T ES2698950T3 ES 2698950 T3 ES2698950 T3 ES 2698950T3 ES 13721746 T ES13721746 T ES 13721746T ES 13721746 T ES13721746 T ES 13721746T ES 2698950 T3 ES2698950 T3 ES 2698950T3

Authority

ES

Spain

Prior art keywords

seq

antibodies

antibody

binding

fxia

Prior art date

2012-05-10

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Active

Links

• Espacenet
• Global Dossier
• Discuss

• 230000027455 binding Effects 0.000 title claims abstract description 79
• 108010080805 Factor XIa Proteins 0.000 title claims abstract description 29
• 108010074864 Factor XI Proteins 0.000 title description 70
• 102100030563 Coagulation factor XI Human genes 0.000 title description 18
• 239000000427 antigen Substances 0.000 claims abstract description 61
• 108091007433 antigens Proteins 0.000 claims abstract description 61
• 102000036639 antigens Human genes 0.000 claims abstract description 61
• 239000012634 fragment Substances 0.000 claims abstract description 56
• 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 45
• 238000000034 method Methods 0.000 claims description 52
• 238000005345 coagulation Methods 0.000 claims description 34
• 230000015271 coagulation Effects 0.000 claims description 33
• 150000001413 amino acids Chemical class 0.000 claims description 31
• 238000011282 treatment Methods 0.000 claims description 29
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
• 238000011321 prophylaxis Methods 0.000 claims description 16
• 201000010099 disease Diseases 0.000 claims description 15
• 239000008194 pharmaceutical composition Substances 0.000 claims description 15
• 150000007523 nucleic acids Chemical class 0.000 claims description 14
• 239000013598 vector Substances 0.000 claims description 13
• 239000003814 drug Substances 0.000 claims description 12
• 108020004707 nucleic acids Proteins 0.000 claims description 10
• 102000039446 nucleic acids Human genes 0.000 claims description 10
• 241001465754 Metazoa Species 0.000 claims description 8
• 241000282412 Homo Species 0.000 claims description 4
• 238000012258 culturing Methods 0.000 claims description 2
• 210000001772 blood platelet Anatomy 0.000 description 38
• 210000004027 cell Anatomy 0.000 description 37
• 108090000623 proteins and genes Proteins 0.000 description 35
• 208000007536 Thrombosis Diseases 0.000 description 34
• 235000001014 amino acid Nutrition 0.000 description 34
• 229940024606 amino acid Drugs 0.000 description 31
• 210000004369 blood Anatomy 0.000 description 29
• 239000008280 blood Substances 0.000 description 29
• 208000032843 Hemorrhage Diseases 0.000 description 26
• 208000034158 bleeding Diseases 0.000 description 26
• 230000000740 bleeding effect Effects 0.000 description 26
• 102000004169 proteins and genes Human genes 0.000 description 26
• 230000010100 anticoagulation Effects 0.000 description 25
• 108020004414 DNA Proteins 0.000 description 22
• 230000000694 effects Effects 0.000 description 21
• 235000018102 proteins Nutrition 0.000 description 21
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 20
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 20
• 108091028043 Nucleic acid sequence Proteins 0.000 description 20
• 238000006243 chemical reaction Methods 0.000 description 20
• 150000001875 compounds Chemical class 0.000 description 20
• 108090000190 Thrombin Proteins 0.000 description 19
• 210000002381 plasma Anatomy 0.000 description 19
• 229960004072 thrombin Drugs 0.000 description 19
• 108090000765 processed proteins & peptides Proteins 0.000 description 18
• 229940126051 coagulation factor XIa Drugs 0.000 description 17
• 239000000243 solution Substances 0.000 description 17
• 108010035532 Collagen Proteins 0.000 description 16
• 102000008186 Collagen Human genes 0.000 description 16
• 230000015572 biosynthetic process Effects 0.000 description 16
• 239000000872 buffer Substances 0.000 description 16
• 229920001436 collagen Polymers 0.000 description 16
• 230000006870 function Effects 0.000 description 16
• 102000004196 processed proteins & peptides Human genes 0.000 description 16
• 239000000126 substance Substances 0.000 description 16
• 108060003951 Immunoglobulin Proteins 0.000 description 15
• 241000283973 Oryctolagus cuniculus Species 0.000 description 15
• 102000018358 immunoglobulin Human genes 0.000 description 15
• 230000005764 inhibitory process Effects 0.000 description 15
• 229920001184 polypeptide Polymers 0.000 description 15
• 238000012360 testing method Methods 0.000 description 15
• 239000003146 anticoagulant agent Substances 0.000 description 14
• 230000023597 hemostasis Effects 0.000 description 14
• 238000009396 hybridization Methods 0.000 description 14
• 239000000203 mixture Substances 0.000 description 14
• 230000017531 blood circulation Effects 0.000 description 12
• 239000003112 inhibitor Substances 0.000 description 12
• 208000002815 pulmonary hypertension Diseases 0.000 description 12
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
• 230000000903 blocking effect Effects 0.000 description 11
• 239000003114 blood coagulation factor Substances 0.000 description 11
• 238000002474 experimental method Methods 0.000 description 11
• 102000015081 Blood Coagulation Factors Human genes 0.000 description 10
• 108010039209 Blood Coagulation Factors Proteins 0.000 description 10
• 238000001994 activation Methods 0.000 description 10
• 230000002785 anti-thrombosis Effects 0.000 description 10
• 231100000673 dose–response relationship Toxicity 0.000 description 10
• 239000012636 effector Substances 0.000 description 10
• 230000001965 increasing effect Effects 0.000 description 10
• 108010047041 Complementarity Determining Regions Proteins 0.000 description 9
• 206010028980 Neoplasm Diseases 0.000 description 9
• 108010000499 Thromboplastin Proteins 0.000 description 9
• 102000002262 Thromboplastin Human genes 0.000 description 9
• 208000027418 Wounds and injury Diseases 0.000 description 9
• 230000004913 activation Effects 0.000 description 9
• UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 9
• 238000001727 in vivo Methods 0.000 description 9
• 238000005259 measurement Methods 0.000 description 9
• 230000008569 process Effects 0.000 description 9
• 239000000047 product Substances 0.000 description 9
• 230000002797 proteolythic effect Effects 0.000 description 9
• 208000010110 spontaneous platelet aggregation Diseases 0.000 description 9
• 238000005406 washing Methods 0.000 description 9
• 101000622137 Homo sapiens P-selectin Proteins 0.000 description 8
• 102100023472 P-selectin Human genes 0.000 description 8
• 108090000113 Plasma Kallikrein Proteins 0.000 description 8
• 230000001580 bacterial effect Effects 0.000 description 8
• 230000023555 blood coagulation Effects 0.000 description 8
• 239000003795 chemical substances by application Substances 0.000 description 8
• 230000006378 damage Effects 0.000 description 8
• 239000013604 expression vector Substances 0.000 description 8
• 239000013612 plasmid Substances 0.000 description 8
• 238000006467 substitution reaction Methods 0.000 description 8
• 230000001225 therapeutic effect Effects 0.000 description 8
• 238000002560 therapeutic procedure Methods 0.000 description 8
• 102000004190 Enzymes Human genes 0.000 description 7
• 108090000790 Enzymes Proteins 0.000 description 7
• 108010073385 Fibrin Proteins 0.000 description 7
• 102000009123 Fibrin Human genes 0.000 description 7
• BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 7
• 102000001399 Kallikrein Human genes 0.000 description 7
• 108060005987 Kallikrein Proteins 0.000 description 7
• 206010040047 Sepsis Diseases 0.000 description 7
• 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 description 7
• 230000003197 catalytic effect Effects 0.000 description 7
• 239000013078 crystal Substances 0.000 description 7
• 238000005516 engineering process Methods 0.000 description 7
• 229940088598 enzyme Drugs 0.000 description 7
• 229950003499 fibrin Drugs 0.000 description 7
• 208000014674 injury Diseases 0.000 description 7
• 230000003993 interaction Effects 0.000 description 7
• 238000004519 manufacturing process Methods 0.000 description 7
• 230000014508 negative regulation of coagulation Effects 0.000 description 7
• 230000037361 pathway Effects 0.000 description 7
• PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 6
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 6
• 238000002965 ELISA Methods 0.000 description 6
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 6
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 6
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 6
• 241000282520 Papio Species 0.000 description 6
• 125000000539 amino acid group Chemical group 0.000 description 6
• 229940079593 drug Drugs 0.000 description 6
• 229940072221 immunoglobulins Drugs 0.000 description 6
• 230000002401 inhibitory effect Effects 0.000 description 6
• 230000035772 mutation Effects 0.000 description 6
• 238000002360 preparation method Methods 0.000 description 6
• 230000002829 reductive effect Effects 0.000 description 6
• 239000000523 sample Substances 0.000 description 6
• 208000013223 septicemia Diseases 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 5
• 241000588724 Escherichia coli Species 0.000 description 5
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
• 101001062768 Homo sapiens Coagulation factor XI Proteins 0.000 description 5
• 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 5
• 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 5
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 5
• 241001504519 Papio ursinus Species 0.000 description 5
• 108010094028 Prothrombin Proteins 0.000 description 5
• 102100027378 Prothrombin Human genes 0.000 description 5
• 108020004511 Recombinant DNA Proteins 0.000 description 5
• 108010022394 Threonine synthase Proteins 0.000 description 5
• 235000004279 alanine Nutrition 0.000 description 5
• 229960000723 ampicillin Drugs 0.000 description 5
• AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 5
• 229940127219 anticoagulant drug Drugs 0.000 description 5
• 238000003556 assay Methods 0.000 description 5
• 239000003153 chemical reaction reagent Substances 0.000 description 5
• 235000018417 cysteine Nutrition 0.000 description 5
• 230000001419 dependent effect Effects 0.000 description 5
• 102000004419 dihydrofolate reductase Human genes 0.000 description 5
• 201000007219 factor XI deficiency Diseases 0.000 description 5
• 229910052739 hydrogen Inorganic materials 0.000 description 5
• 239000001257 hydrogen Substances 0.000 description 5
• 238000003199 nucleic acid amplification method Methods 0.000 description 5
• 230000036961 partial effect Effects 0.000 description 5
• 230000010412 perfusion Effects 0.000 description 5
• 238000001556 precipitation Methods 0.000 description 5
• 241000894007 species Species 0.000 description 5
• 230000002885 thrombogenetic effect Effects 0.000 description 5
• 238000001890 transfection Methods 0.000 description 5
• 239000003981 vehicle Substances 0.000 description 5
• 208000026151 Chronic thromboembolic pulmonary hypertension Diseases 0.000 description 4
• 108010074860 Factor Xa Proteins 0.000 description 4
• 108010049003 Fibrinogen Proteins 0.000 description 4
• 102000008946 Fibrinogen Human genes 0.000 description 4
• 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 4
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
• 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 4
• 229910021578 Iron(III) chloride Inorganic materials 0.000 description 4
• 241001529936 Murinae Species 0.000 description 4
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 4
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 4
• 102000012479 Serine Proteases Human genes 0.000 description 4
• 108010022999 Serine Proteases Proteins 0.000 description 4
• 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 4
• 239000007983 Tris buffer Substances 0.000 description 4
• 206010047249 Venous thrombosis Diseases 0.000 description 4
• 206010000891 acute myocardial infarction Diseases 0.000 description 4
• 230000003321 amplification Effects 0.000 description 4
• 238000004458 analytical method Methods 0.000 description 4
• 235000009582 asparagine Nutrition 0.000 description 4
• 229960001230 asparagine Drugs 0.000 description 4
• 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 4
• 239000011324 bead Substances 0.000 description 4
• 201000011510 cancer Diseases 0.000 description 4
• 238000005119 centrifugation Methods 0.000 description 4
• 238000004587 chromatography analysis Methods 0.000 description 4
• 230000000875 corresponding effect Effects 0.000 description 4
• 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 4
• 230000008021 deposition Effects 0.000 description 4
• 238000013461 design Methods 0.000 description 4
• 238000011161 development Methods 0.000 description 4
• 238000000502 dialysis Methods 0.000 description 4
• 239000000539 dimer Substances 0.000 description 4
• 229940012952 fibrinogen Drugs 0.000 description 4
• 238000000684 flow cytometry Methods 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• 238000001631 haemodialysis Methods 0.000 description 4
• 230000000322 hemodialysis Effects 0.000 description 4
• 238000011534 incubation Methods 0.000 description 4
• 208000015181 infectious disease Diseases 0.000 description 4
• 230000000977 initiatory effect Effects 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 4
• 210000004962 mammalian cell Anatomy 0.000 description 4
• 239000003550 marker Substances 0.000 description 4
• 230000001404 mediated effect Effects 0.000 description 4
• 235000013930 proline Nutrition 0.000 description 4
• 238000011160 research Methods 0.000 description 4
• 235000004400 serine Nutrition 0.000 description 4
• 239000011780 sodium chloride Substances 0.000 description 4
• 239000002904 solvent Substances 0.000 description 4
• 239000000758 substrate Substances 0.000 description 4
• 239000006228 supernatant Substances 0.000 description 4
• 230000009885 systemic effect Effects 0.000 description 4
• 230000001732 thrombotic effect Effects 0.000 description 4
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
• 102100022641 Coagulation factor IX Human genes 0.000 description 3
• 241000701022 Cytomegalovirus Species 0.000 description 3
• 206010051055 Deep vein thrombosis Diseases 0.000 description 3
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 3
• 229920002307 Dextran Polymers 0.000 description 3
• 102000010911 Enzyme Precursors Human genes 0.000 description 3
• 108010062466 Enzyme Precursors Proteins 0.000 description 3
• 108010076282 Factor IX Proteins 0.000 description 3
• 108010071241 Factor XIIa Proteins 0.000 description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
• 239000004472 Lysine Substances 0.000 description 3
• 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 3
• 102100034869 Plasma kallikrein Human genes 0.000 description 3
• 208000010378 Pulmonary Embolism Diseases 0.000 description 3
• 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 3
• 208000014777 Pulmonary venoocclusive disease Diseases 0.000 description 3
• XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 3
• 230000001154 acute effect Effects 0.000 description 3
• 239000002671 adjuvant Substances 0.000 description 3
• 229960004676 antithrombotic agent Drugs 0.000 description 3
• 230000004071 biological effect Effects 0.000 description 3
• 229940019700 blood coagulation factors Drugs 0.000 description 3
• 210000004204 blood vessel Anatomy 0.000 description 3
• 238000004113 cell culture Methods 0.000 description 3
• 230000000295 complement effect Effects 0.000 description 3
• 208000011664 congenital factor XI deficiency Diseases 0.000 description 3
• 238000007796 conventional method Methods 0.000 description 3
• 229910052805 deuterium Inorganic materials 0.000 description 3
• 208000009190 disseminated intravascular coagulation Diseases 0.000 description 3
• 239000003937 drug carrier Substances 0.000 description 3
• -1 e.g. Proteins 0.000 description 3
• 230000008030 elimination Effects 0.000 description 3
• 238000003379 elimination reaction Methods 0.000 description 3
• 239000003623 enhancer Substances 0.000 description 3
• 238000011156 evaluation Methods 0.000 description 3
• 229920000295 expanded polytetrafluoroethylene Polymers 0.000 description 3
• 108020001507 fusion proteins Proteins 0.000 description 3
• 102000037865 fusion proteins Human genes 0.000 description 3
• 239000008103 glucose Substances 0.000 description 3
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
• 235000004554 glutamine Nutrition 0.000 description 3
• 230000002439 hemostatic effect Effects 0.000 description 3
• 235000014304 histidine Nutrition 0.000 description 3
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 238000003780 insertion Methods 0.000 description 3
• 230000037431 insertion Effects 0.000 description 3
• 230000006623 intrinsic pathway Effects 0.000 description 3
• 238000002955 isolation Methods 0.000 description 3
• 235000005772 leucine Nutrition 0.000 description 3
• 235000018977 lysine Nutrition 0.000 description 3
• 238000013507 mapping Methods 0.000 description 3
• 230000007246 mechanism Effects 0.000 description 3
• 238000002156 mixing Methods 0.000 description 3
• 238000010369 molecular cloning Methods 0.000 description 3
• 230000003472 neutralizing effect Effects 0.000 description 3
• 238000007911 parenteral administration Methods 0.000 description 3
• 238000002823 phage display Methods 0.000 description 3
• 230000000144 pharmacologic effect Effects 0.000 description 3
• 230000010118 platelet activation Effects 0.000 description 3
• 102000040430 polynucleotide Human genes 0.000 description 3
• 108091033319 polynucleotide Proteins 0.000 description 3
• 239000002157 polynucleotide Substances 0.000 description 3
• 230000002265 prevention Effects 0.000 description 3
• 229940039716 prothrombin Drugs 0.000 description 3
• 230000002685 pulmonary effect Effects 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• 108020003175 receptors Proteins 0.000 description 3
• 102000005962 receptors Human genes 0.000 description 3
• 230000009467 reduction Effects 0.000 description 3
• 230000001105 regulatory effect Effects 0.000 description 3
• 230000010076 replication Effects 0.000 description 3
• 238000012552 review Methods 0.000 description 3
• 230000035945 sensitivity Effects 0.000 description 3
• 229910052710 silicon Inorganic materials 0.000 description 3
• 239000010703 silicon Substances 0.000 description 3
• 239000001509 sodium citrate Substances 0.000 description 3
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 3
• 238000001356 surgical procedure Methods 0.000 description 3
• 229940124597 therapeutic agent Drugs 0.000 description 3
• 230000009424 thromboembolic effect Effects 0.000 description 3
• 230000002537 thrombolytic effect Effects 0.000 description 3
• 230000002792 vascular Effects 0.000 description 3
• 230000002861 ventricular Effects 0.000 description 3
• 210000005253 yeast cell Anatomy 0.000 description 3
• HRYITGOEDRTTLM-FRSCJGFNSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]butanediamide Chemical compound NC(N)=NCCC[C@@H](C(=O)N[C@@H](CC(N)=O)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)CC1=CC=CC=C1 HRYITGOEDRTTLM-FRSCJGFNSA-N 0.000 description 2
• ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 2
• NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 2
• FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
• 208000024827 Alzheimer disease Diseases 0.000 description 2
• 108010039627 Aprotinin Proteins 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 206010003658 Atrial Fibrillation Diseases 0.000 description 2
• 241000894006 Bacteria Species 0.000 description 2
• 102100025698 Cytosolic carboxypeptidase 4 Human genes 0.000 description 2
• 102000053602 DNA Human genes 0.000 description 2
• 208000005189 Embolism Diseases 0.000 description 2
• 206010014522 Embolism venous Diseases 0.000 description 2
• 241000283073 Equus caballus Species 0.000 description 2
• 108010080865 Factor XII Proteins 0.000 description 2
• 102000000429 Factor XII Human genes 0.000 description 2
• 108010087819 Fc receptors Proteins 0.000 description 2
• 102000009109 Fc receptors Human genes 0.000 description 2
• 206010016717 Fistula Diseases 0.000 description 2
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
• 239000004471 Glycine Substances 0.000 description 2
• 101000932590 Homo sapiens Cytosolic carboxypeptidase 4 Proteins 0.000 description 2
• 208000029523 Interstitial Lung disease Diseases 0.000 description 2
• YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 2
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 2
• 101001033003 Mus musculus Granzyme F Proteins 0.000 description 2
• 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 2
• 108010001014 Plasminogen Activators Proteins 0.000 description 2
• 102000001938 Plasminogen Activators Human genes 0.000 description 2
• 239000004365 Protease Substances 0.000 description 2
• 208000031467 Pulmonary capillary hemangiomatosis Diseases 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• 108010090804 Streptavidin Proteins 0.000 description 2
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
• 239000004473 Threonine Substances 0.000 description 2
• 208000001435 Thromboembolism Diseases 0.000 description 2
• 208000034841 Thrombotic Microangiopathies Diseases 0.000 description 2
• 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 2
• 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 2
• 208000032109 Transient ischaemic attack Diseases 0.000 description 2
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
• 230000005856 abnormality Effects 0.000 description 2
• 238000009825 accumulation Methods 0.000 description 2
• 239000002253 acid Substances 0.000 description 2
• 230000003213 activating effect Effects 0.000 description 2
• 239000004480 active ingredient Substances 0.000 description 2
• 206010069351 acute lung injury Diseases 0.000 description 2
• 239000000654 additive Substances 0.000 description 2
• 239000000674 adrenergic antagonist Substances 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 239000005557 antagonist Substances 0.000 description 2
• 230000000702 anti-platelet effect Effects 0.000 description 2
• 229940127218 antiplatelet drug Drugs 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• 229960004405 aprotinin Drugs 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 238000000149 argon plasma sintering Methods 0.000 description 2
• 210000001367 artery Anatomy 0.000 description 2
• 235000003704 aspartic acid Nutrition 0.000 description 2
• 238000003149 assay kit Methods 0.000 description 2
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 230000033228 biological regulation Effects 0.000 description 2
• 239000012472 biological sample Substances 0.000 description 2
• 238000004820 blood count Methods 0.000 description 2
• 239000007975 buffered saline Substances 0.000 description 2
• 239000001506 calcium phosphate Substances 0.000 description 2
• 229910000389 calcium phosphate Inorganic materials 0.000 description 2
• 235000011010 calcium phosphates Nutrition 0.000 description 2
• 210000001715 carotid artery Anatomy 0.000 description 2
• 210000001168 carotid artery common Anatomy 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 2
• 238000003776 cleavage reaction Methods 0.000 description 2
• 239000011248 coating agent Substances 0.000 description 2
• 238000000576 coating method Methods 0.000 description 2
• 230000002860 competitive effect Effects 0.000 description 2
• 230000009918 complex formation Effects 0.000 description 2
• 238000010276 construction Methods 0.000 description 2
• 208000029078 coronary artery disease Diseases 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• ZOOGRGPOEVQQDX-KHLHZJAASA-N cyclic guanosine monophosphate Chemical compound C([C@H]1O2)O[P@](O)(=O)O[C@@H]1[C@H](O)[C@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-KHLHZJAASA-N 0.000 description 2
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
• 230000007423 decrease Effects 0.000 description 2
• 230000007812 deficiency Effects 0.000 description 2
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
• 238000004520 electroporation Methods 0.000 description 2
• 230000002255 enzymatic effect Effects 0.000 description 2
• 210000003527 eukaryotic cell Anatomy 0.000 description 2
• 238000002618 extracorporeal membrane oxygenation Methods 0.000 description 2
• 230000006624 extrinsic pathway Effects 0.000 description 2
• 229960004222 factor ix Drugs 0.000 description 2
• 230000020764 fibrinolysis Effects 0.000 description 2
• 230000003890 fistula Effects 0.000 description 2
• MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
• 235000013922 glutamic acid Nutrition 0.000 description 2
• 239000004220 glutamic acid Substances 0.000 description 2
• 208000007345 glycogen storage disease Diseases 0.000 description 2
• 239000001963 growth medium Substances 0.000 description 2
• 238000004128 high performance liquid chromatography Methods 0.000 description 2
• JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
• 230000002209 hydrophobic effect Effects 0.000 description 2
• 230000001976 improved effect Effects 0.000 description 2
• ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 2
• 238000001361 intraarterial administration Methods 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 238000007912 intraperitoneal administration Methods 0.000 description 2
• 238000007913 intrathecal administration Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 238000007914 intraventricular administration Methods 0.000 description 2
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
• 229960000310 isoleucine Drugs 0.000 description 2
• 235000014705 isoleucine Nutrition 0.000 description 2
• 229960003299 ketamine Drugs 0.000 description 2
• 238000002372 labelling Methods 0.000 description 2
• PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 2
• 238000012423 maintenance Methods 0.000 description 2
• 238000004949 mass spectrometry Methods 0.000 description 2
• 230000035800 maturation Effects 0.000 description 2
• 235000006109 methionine Nutrition 0.000 description 2
• 229930182817 methionine Natural products 0.000 description 2
• 229960000485 methotrexate Drugs 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 208000010125 myocardial infarction Diseases 0.000 description 2
• 238000006386 neutralization reaction Methods 0.000 description 2
• PVHUJELLJLJGLN-UHFFFAOYSA-N nitrendipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC([N+]([O-])=O)=C1 PVHUJELLJLJGLN-UHFFFAOYSA-N 0.000 description 2
• 238000002515 oligonucleotide synthesis Methods 0.000 description 2
• 230000008520 organization Effects 0.000 description 2
• 244000052769 pathogen Species 0.000 description 2
• 230000001575 pathological effect Effects 0.000 description 2
• 230000002093 peripheral effect Effects 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
• 235000008729 phenylalanine Nutrition 0.000 description 2
• 229940127126 plasminogen activator Drugs 0.000 description 2
• 239000000106 platelet aggregation inhibitor Substances 0.000 description 2
• 230000031915 positive regulation of coagulation Effects 0.000 description 2
• TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 2
• 239000002243 precursor Substances 0.000 description 2
• 238000012545 processing Methods 0.000 description 2
• 210000001236 prokaryotic cell Anatomy 0.000 description 2
• AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
• 230000006337 proteolytic cleavage Effects 0.000 description 2
• 210000001147 pulmonary artery Anatomy 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 206010039073 rheumatoid arthritis Diseases 0.000 description 2
• 230000007017 scission Effects 0.000 description 2
• 230000003248 secreting effect Effects 0.000 description 2
• 229920002379 silicone rubber Polymers 0.000 description 2
• 239000004945 silicone rubber Substances 0.000 description 2
• RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 2
• 230000009870 specific binding Effects 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 208000011580 syndromic disease Diseases 0.000 description 2
• 235000008521 threonine Nutrition 0.000 description 2
• 108010063955 thrombin receptor peptide (42-47) Proteins 0.000 description 2
• 210000001519 tissue Anatomy 0.000 description 2
• 229960000187 tissue plasminogen activator Drugs 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 201000010875 transient cerebral ischemia Diseases 0.000 description 2
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
• 235000002374 tyrosine Nutrition 0.000 description 2
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
• 241000701161 unidentified adenovirus Species 0.000 description 2
• 239000004474 valine Substances 0.000 description 2
• 235000014393 valine Nutrition 0.000 description 2
• 208000019553 vascular disease Diseases 0.000 description 2
• 208000004043 venous thromboembolism Diseases 0.000 description 2
• 230000003612 virological effect Effects 0.000 description 2
• 239000002699 waste material Substances 0.000 description 2
• SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
• UVGHPGOONBRLCX-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-[5-(2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl)pentanoylamino]hexanoate Chemical compound S1CC2NC(=O)NC2C1CCCCC(=O)NCCCCCC(=O)ON1C(=O)CCC1=O UVGHPGOONBRLCX-UHFFFAOYSA-N 0.000 description 1
• WXPZDDCNKXMOMC-AVGNSLFASA-N (2s)-1-[(2s)-2-[[(2s)-1-(2-aminoacetyl)pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carboxylic acid Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@H](C(O)=O)CCC1 WXPZDDCNKXMOMC-AVGNSLFASA-N 0.000 description 1
• BIDNLKIUORFRQP-XYGFDPSESA-N (2s,4s)-4-cyclohexyl-1-[2-[[(1s)-2-methyl-1-propanoyloxypropoxy]-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C([P@@](=O)(O[C@H](OC(=O)CC)C(C)C)CC(=O)N1[C@@H](C[C@H](C1)C1CCCCC1)C(O)=O)CCCC1=CC=CC=C1 BIDNLKIUORFRQP-XYGFDPSESA-N 0.000 description 1
• METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
• TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 description 1
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
• UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 1
• SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
• KLDBMPMWBVTYGW-AIDJSRAFSA-N 2-aminoacetic acid (2S)-2-amino-3-hydroxypropanoic acid Chemical compound NCC(O)=O.NCC(O)=O.NCC(O)=O.NCC(O)=O.OC[C@H](N)C(O)=O KLDBMPMWBVTYGW-AIDJSRAFSA-N 0.000 description 1
• CFWRDBDJAOHXSH-SECBINFHSA-N 2-azaniumylethyl [(2r)-2,3-diacetyloxypropyl] phosphate Chemical compound CC(=O)OC[C@@H](OC(C)=O)COP(O)(=O)OCCN CFWRDBDJAOHXSH-SECBINFHSA-N 0.000 description 1
• BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
• YANRNHYHEYMCOY-QTTLMPKLSA-N 5-[2-[3-[[(2r)-4-[[[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-2-hydroxy-3,3-dimethylbutanoyl]amino]propanoylamino]ethylsulfanyl]-3-hydroxy-4-methyl-5-oxopentanoic acid Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C(C(O)CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 YANRNHYHEYMCOY-QTTLMPKLSA-N 0.000 description 1
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• 206010002091 Anaesthesia Diseases 0.000 description 1
• 206010002383 Angina Pectoris Diseases 0.000 description 1
• 102000008873 Angiotensin II receptor Human genes 0.000 description 1
• 108050000824 Angiotensin II receptor Proteins 0.000 description 1
• 108010032595 Antibody Binding Sites Proteins 0.000 description 1
• 208000019901 Anxiety disease Diseases 0.000 description 1
• 102000000443 Apple domains Human genes 0.000 description 1
• 108050008958 Apple domains Proteins 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 206010003178 Arterial thrombosis Diseases 0.000 description 1
• 206010003226 Arteriovenous fistula Diseases 0.000 description 1
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
• 201000001320 Atherosclerosis Diseases 0.000 description 1
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
• XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
• 244000063299 Bacillus subtilis Species 0.000 description 1
• 235000014469 Bacillus subtilis Nutrition 0.000 description 1
• XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 201000006474 Brain Ischemia Diseases 0.000 description 1
• RHLJLALHBZGAFM-UHFFFAOYSA-N Bunazosinum Chemical compound C1CN(C(=O)CCC)CCCN1C1=NC(N)=C(C=C(OC)C(OC)=C2)C2=N1 RHLJLALHBZGAFM-UHFFFAOYSA-N 0.000 description 1
• 108010075254 C-Peptide Proteins 0.000 description 1
• 239000002083 C09CA01 - Losartan Substances 0.000 description 1
• 239000002080 C09CA02 - Eprosartan Substances 0.000 description 1
• 239000004072 C09CA03 - Valsartan Substances 0.000 description 1
• 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
• 239000002053 C09CA06 - Candesartan Substances 0.000 description 1
• 108090000312 Calcium Channels Proteins 0.000 description 1
• 102000003922 Calcium Channels Human genes 0.000 description 1
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
• 241000282836 Camelus dromedarius Species 0.000 description 1
• 108090000201 Carboxypeptidase B2 Proteins 0.000 description 1
• 102100035023 Carboxypeptidase B2 Human genes 0.000 description 1
• 231100000023 Cell-mediated cytotoxicity Toxicity 0.000 description 1
• 206010057250 Cell-mediated cytotoxicity Diseases 0.000 description 1
• 206010008120 Cerebral ischaemia Diseases 0.000 description 1
• JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 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
• 102100023804 Coagulation factor VII Human genes 0.000 description 1
• 102100029117 Coagulation factor X Human genes 0.000 description 1
• 241001429175 Colitis phage Species 0.000 description 1
• 102000012422 Collagen Type I Human genes 0.000 description 1
• 108010022452 Collagen Type I Proteins 0.000 description 1
• 208000027932 Collagen disease Diseases 0.000 description 1
• 102000014447 Complement C1q Human genes 0.000 description 1
• 108010078043 Complement C1q Proteins 0.000 description 1
• 108020004635 Complementary DNA Proteins 0.000 description 1
• 206010010356 Congenital anomaly Diseases 0.000 description 1
• 241000557626 Corvus corax Species 0.000 description 1
• 241000699802 Cricetulus griseus Species 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• 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
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• 230000006820 DNA synthesis Effects 0.000 description 1
• 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
• 206010012689 Diabetic retinopathy Diseases 0.000 description 1
• BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
• JRWZLRBJNMZMFE-UHFFFAOYSA-N Dobutamine Chemical compound C=1C=C(O)C(O)=CC=1CCNC(C)CCC1=CC=C(O)C=C1 JRWZLRBJNMZMFE-UHFFFAOYSA-N 0.000 description 1
• 206010058314 Dysplasia Diseases 0.000 description 1
• 238000012286 ELISA Assay Methods 0.000 description 1
• 206010014009 Ear haemorrhage Diseases 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 206010014498 Embolic stroke Diseases 0.000 description 1
• 241000196324 Embryophyta Species 0.000 description 1
• 206010048554 Endothelial dysfunction Diseases 0.000 description 1
• YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
• 108010023321 Factor VII Proteins 0.000 description 1
• 108010014173 Factor X Proteins 0.000 description 1
• 208000004248 Familial Primary Pulmonary Hypertension Diseases 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 241000724791 Filamentous phage Species 0.000 description 1
• 241000233866 Fungi Species 0.000 description 1
• 208000015872 Gaucher disease Diseases 0.000 description 1
• 206010018338 Glioma Diseases 0.000 description 1
• 108090000288 Glycoproteins Proteins 0.000 description 1
• 102000003886 Glycoproteins Human genes 0.000 description 1
• 108060003393 Granulin Proteins 0.000 description 1
• 208000031886 HIV Infections Diseases 0.000 description 1
• 239000012981 Hank's balanced salt solution Substances 0.000 description 1
• 229920001499 Heparinoid Polymers 0.000 description 1
• 208000000857 Hepatic Insufficiency Diseases 0.000 description 1
• 206010019663 Hepatic failure Diseases 0.000 description 1
• 206010019668 Hepatic fibrosis Diseases 0.000 description 1
• 208000021124 Heritable pulmonary arterial hypertension Diseases 0.000 description 1
• 241000238631 Hexapoda Species 0.000 description 1
• 108010000487 High-Molecular-Weight Kininogen Proteins 0.000 description 1
• 108010007267 Hirudins Proteins 0.000 description 1
• 102000007625 Hirudins Human genes 0.000 description 1
• 101001015004 Homo sapiens Integrin beta-3 Proteins 0.000 description 1
• 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
• 206010020772 Hypertension Diseases 0.000 description 1
• 206010021143 Hypoxia Diseases 0.000 description 1
• 208000020875 Idiopathic pulmonary arterial hypertension Diseases 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
• 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
• 206010061216 Infarction Diseases 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 108020005350 Initiator Codon Proteins 0.000 description 1
• 102100032999 Integrin beta-3 Human genes 0.000 description 1
• 208000032382 Ischaemic stroke Diseases 0.000 description 1
• 102100035792 Kininogen-1 Human genes 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• 201000005099 Langerhans cell histiocytosis Diseases 0.000 description 1
• 108090001090 Lectins Proteins 0.000 description 1
• 102000004856 Lectins Human genes 0.000 description 1
• 101000701051 Legionella pneumophila Zinc metalloproteinase Proteins 0.000 description 1
• 108010007859 Lisinopril Proteins 0.000 description 1
• 208000019693 Lung disease Diseases 0.000 description 1
• 206010025219 Lymphangioma Diseases 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 238000007476 Maximum Likelihood Methods 0.000 description 1
• 206010027476 Metastases Diseases 0.000 description 1
• 206010027527 Microangiopathic haemolytic anaemia Diseases 0.000 description 1
• 208000010718 Multiple Organ Failure Diseases 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• 208000014767 Myeloproliferative disease Diseases 0.000 description 1
• 241001045988 Neogene Species 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 208000025966 Neurological disease Diseases 0.000 description 1
• SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
• 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
• 102000004316 Oxidoreductases Human genes 0.000 description 1
• 108090000854 Oxidoreductases Proteins 0.000 description 1
• 239000008118 PEG 6000 Substances 0.000 description 1
• 206010033645 Pancreatitis Diseases 0.000 description 1
• 108090000526 Papain Proteins 0.000 description 1
• 102000057297 Pepsin A Human genes 0.000 description 1
• 108090000284 Pepsin A Proteins 0.000 description 1
• 102000035195 Peptidases Human genes 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• 108010067902 Peptide Library Proteins 0.000 description 1
• 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 1
• 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 1
• 241000009328 Perro Species 0.000 description 1
• 241000305201 Phalaenoides glycinae Species 0.000 description 1
• UJEWTUDSLQGTOA-UHFFFAOYSA-N Piretanide Chemical compound C=1C=CC=CC=1OC=1C(S(=O)(=O)N)=CC(C(O)=O)=CC=1N1CCCC1 UJEWTUDSLQGTOA-UHFFFAOYSA-N 0.000 description 1
• 206010035226 Plasma cell myeloma Diseases 0.000 description 1
• 229920002538 Polyethylene Glycol 20000 Polymers 0.000 description 1
• 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 229920001213 Polysorbate 20 Polymers 0.000 description 1
• TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• 101800004937 Protein C Proteins 0.000 description 1
• 102000017975 Protein C Human genes 0.000 description 1
• 241000589516 Pseudomonas Species 0.000 description 1
• 208000001647 Renal Insufficiency Diseases 0.000 description 1
• 206010038548 Renal vein thrombosis Diseases 0.000 description 1
• 206010038563 Reocclusion Diseases 0.000 description 1
• RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
• 208000006117 ST-elevation myocardial infarction Diseases 0.000 description 1
• 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
• 101800001700 Saposin-D Proteins 0.000 description 1
• 206010040621 Shunt occlusion Diseases 0.000 description 1
• 206010059054 Shunt thrombosis Diseases 0.000 description 1
• 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
• 102000007637 Soluble Guanylyl Cyclase Human genes 0.000 description 1
• 108010007205 Soluble Guanylyl Cyclase Proteins 0.000 description 1
• 208000007718 Stable Angina Diseases 0.000 description 1
• 241000191940 Staphylococcus Species 0.000 description 1
• 108010023197 Streptokinase Proteins 0.000 description 1
• 241000187747 Streptomyces Species 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
• 239000012505 Superdex™ Substances 0.000 description 1
• 241000282898 Sus scrofa Species 0.000 description 1
• 108091008874 T cell receptors Proteins 0.000 description 1
• 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
• 108020005038 Terminator Codon Proteins 0.000 description 1
• 206010043647 Thrombotic Stroke Diseases 0.000 description 1
• 208000024799 Thyroid disease Diseases 0.000 description 1
• NGBFQHCMQULJNZ-UHFFFAOYSA-N Torsemide Chemical compound CC(C)NC(=O)NS(=O)(=O)C1=CN=CC=C1NC1=CC=CC(C)=C1 NGBFQHCMQULJNZ-UHFFFAOYSA-N 0.000 description 1
• 101710120037 Toxin CcdB Proteins 0.000 description 1
• 108090000631 Trypsin Proteins 0.000 description 1
• 102000004142 Trypsin Human genes 0.000 description 1
• 208000007814 Unstable Angina Diseases 0.000 description 1
• 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
• 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
• GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 1
• 102000002852 Vasopressins Human genes 0.000 description 1
• 108010004977 Vasopressins Proteins 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• 108010059382 Zea mays trypsin inhibitor Proteins 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• 229960002122 acebutolol Drugs 0.000 description 1
• GOEMGAFJFRBGGG-UHFFFAOYSA-N acebutolol Chemical compound CCCC(=O)NC1=CC=C(OCC(O)CNC(C)C)C(C(C)=O)=C1 GOEMGAFJFRBGGG-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 229960001138 acetylsalicylic acid Drugs 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 229940092980 adalat Drugs 0.000 description 1
• 238000001042 affinity chromatography Methods 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 206010064930 age-related macular degeneration Diseases 0.000 description 1
• 238000013019 agitation Methods 0.000 description 1
• 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
• 150000001295 alanines Chemical class 0.000 description 1
• 230000003281 allosteric effect Effects 0.000 description 1
• 102000030619 alpha-1 Adrenergic Receptor Human genes 0.000 description 1
• 108020004102 alpha-1 Adrenergic Receptor Proteins 0.000 description 1
• 229960002213 alprenolol Drugs 0.000 description 1
• PAZJSJFMUHDSTF-UHFFFAOYSA-N alprenolol Chemical compound CC(C)NCC(O)COC1=CC=CC=C1CC=C PAZJSJFMUHDSTF-UHFFFAOYSA-N 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• 208000008445 altitude sickness Diseases 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• XSDQTOBWRPYKKA-UHFFFAOYSA-N amiloride Chemical compound NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N XSDQTOBWRPYKKA-UHFFFAOYSA-N 0.000 description 1
• 229960002576 amiloride Drugs 0.000 description 1
• BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
• 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
• 235000011130 ammonium sulphate Nutrition 0.000 description 1
• 230000037005 anaesthesia Effects 0.000 description 1
• 230000003444 anaesthetic effect Effects 0.000 description 1
• 238000002399 angioplasty Methods 0.000 description 1
• 125000000129 anionic group Chemical group 0.000 description 1
• 230000002744 anti-aggregatory effect Effects 0.000 description 1
• 230000001455 anti-clotting effect Effects 0.000 description 1
• 230000000843 anti-fungal effect Effects 0.000 description 1
• 230000003276 anti-hypertensive effect Effects 0.000 description 1
• 230000001028 anti-proliverative effect Effects 0.000 description 1
• 230000000840 anti-viral effect Effects 0.000 description 1
• 230000005875 antibody response Effects 0.000 description 1
• 229940127090 anticoagulant agent Drugs 0.000 description 1
• 229940121375 antifungal agent Drugs 0.000 description 1
• 230000000890 antigenic effect Effects 0.000 description 1
• 230000006502 antiplatelets effects Effects 0.000 description 1
• 239000004019 antithrombin Substances 0.000 description 1
• 230000036506 anxiety Effects 0.000 description 1
• 210000001765 aortic valve Anatomy 0.000 description 1
• KXNPVXPOPUZYGB-XYVMCAHJSA-N argatroban Chemical compound OC(=O)[C@H]1C[C@H](C)CCN1C(=O)[C@H](CCCN=C(N)N)NS(=O)(=O)C1=CC=CC2=C1NC[C@H](C)C2 KXNPVXPOPUZYGB-XYVMCAHJSA-N 0.000 description 1
• 229960003856 argatroban Drugs 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 1
• 229960002274 atenolol Drugs 0.000 description 1
• 230000003143 atherosclerotic effect Effects 0.000 description 1
• 229960005370 atorvastatin Drugs 0.000 description 1
• FQCKMBLVYCEXJB-MNSAWQCASA-L atorvastatin calcium Chemical compound [Ca+2].C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1.C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 FQCKMBLVYCEXJB-MNSAWQCASA-L 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 229960004530 benazepril Drugs 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 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 1
• 229960004324 betaxolol Drugs 0.000 description 1
• CHDPSNLJFOQTRK-UHFFFAOYSA-N betaxolol hydrochloride Chemical compound [Cl-].C1=CC(OCC(O)C[NH2+]C(C)C)=CC=C1CCOCC1CC1 CHDPSNLJFOQTRK-UHFFFAOYSA-N 0.000 description 1
• 230000001588 bifunctional effect Effects 0.000 description 1
• 238000004166 bioassay Methods 0.000 description 1
• 230000003115 biocidal effect Effects 0.000 description 1
• 230000031018 biological processes and functions Effects 0.000 description 1
• 108091006004 biotinylated proteins Proteins 0.000 description 1
• 229960002781 bisoprolol Drugs 0.000 description 1
• VHYCDWMUTMEGQY-UHFFFAOYSA-N bisoprolol Chemical compound CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1 VHYCDWMUTMEGQY-UHFFFAOYSA-N 0.000 description 1
• 108010055460 bivalirudin Proteins 0.000 description 1
• OIRCOABEOLEUMC-GEJPAHFPSA-N bivalirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 OIRCOABEOLEUMC-GEJPAHFPSA-N 0.000 description 1
• 229960001500 bivalirudin Drugs 0.000 description 1
• 239000010836 blood and blood product Substances 0.000 description 1
• 229940125691 blood product Drugs 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 229960004064 bumetanide Drugs 0.000 description 1
• MAEIEVLCKWDQJH-UHFFFAOYSA-N bumetanide Chemical compound CCCCNC1=CC(C(O)=O)=CC(S(N)(=O)=O)=C1OC1=CC=CC=C1 MAEIEVLCKWDQJH-UHFFFAOYSA-N 0.000 description 1
• 229960002467 bunazosin Drugs 0.000 description 1
• 238000010804 cDNA synthesis Methods 0.000 description 1
• 239000001110 calcium chloride Substances 0.000 description 1
• 229910001628 calcium chloride Inorganic materials 0.000 description 1
• 229960000932 candesartan Drugs 0.000 description 1
• SGZAIDDFHDDFJU-UHFFFAOYSA-N candesartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SGZAIDDFHDDFJU-UHFFFAOYSA-N 0.000 description 1
• 229960000830 captopril Drugs 0.000 description 1
• FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 230000001269 cardiogenic effect Effects 0.000 description 1
• 230000002612 cardiopulmonary effect Effects 0.000 description 1
• 210000000748 cardiovascular system Anatomy 0.000 description 1
• 229960001222 carteolol Drugs 0.000 description 1
• LWAFSWPYPHEXKX-UHFFFAOYSA-N carteolol Chemical compound N1C(=O)CCC2=C1C=CC=C2OCC(O)CNC(C)(C)C LWAFSWPYPHEXKX-UHFFFAOYSA-N 0.000 description 1
• 229960004195 carvedilol Drugs 0.000 description 1
• NPAKNKYSJIDKMW-UHFFFAOYSA-N carvedilol Chemical compound COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=NC3=CC=C[CH]C3=C12 NPAKNKYSJIDKMW-UHFFFAOYSA-N 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 108020001778 catalytic domains Proteins 0.000 description 1
• 238000005277 cation exchange chromatography Methods 0.000 description 1
• 230000005890 cell-mediated cytotoxicity Effects 0.000 description 1
• 230000002490 cerebral effect Effects 0.000 description 1
• 206010008118 cerebral infarction Diseases 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 238000001311 chemical methods and process Methods 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 208000020832 chronic kidney disease Diseases 0.000 description 1
• 229960005025 cilazapril Drugs 0.000 description 1
• HHHKFGXWKKUNCY-FHWLQOOXSA-N cilazapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N2[C@@H](CCCN2CCC1)C(O)=O)=O)CC1=CC=CC=C1 HHHKFGXWKKUNCY-FHWLQOOXSA-N 0.000 description 1
• 230000004087 circulation Effects 0.000 description 1
• 238000005352 clarification Methods 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 239000013599 cloning vector Substances 0.000 description 1
• 238000011260 co-administration Methods 0.000 description 1
• 229940105774 coagulation factor ix Drugs 0.000 description 1
• 229940105756 coagulation factor x Drugs 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 238000012875 competitive assay Methods 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 230000021615 conjugation Effects 0.000 description 1
• 210000004351 coronary vessel Anatomy 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 239000013632 covalent dimer Substances 0.000 description 1
• 230000037029 cross reaction Effects 0.000 description 1
• 230000009260 cross reactivity Effects 0.000 description 1
• 239000000287 crude extract Substances 0.000 description 1
• 231100000135 cytotoxicity Toxicity 0.000 description 1
• 230000003013 cytotoxicity Effects 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 238000012217 deletion Methods 0.000 description 1
• 230000037430 deletion Effects 0.000 description 1
• 238000001212 derivatisation Methods 0.000 description 1
• 238000011033 desalting Methods 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• 239000000032 diagnostic agent Substances 0.000 description 1
• 229940039227 diagnostic agent Drugs 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
• MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
• 230000029087 digestion Effects 0.000 description 1
• VQKLRVZQQYVIJW-UHFFFAOYSA-N dihydralazine Chemical compound C1=CC=C2C(NN)=NN=C(NN)C2=C1 VQKLRVZQQYVIJW-UHFFFAOYSA-N 0.000 description 1
• 229960002877 dihydralazine Drugs 0.000 description 1
• 125000004925 dihydropyridyl group Chemical class N1(CC=CC=C1)* 0.000 description 1
• HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
• 229960004166 diltiazem Drugs 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• 230000006334 disulfide bridging Effects 0.000 description 1
• 239000002934 diuretic Substances 0.000 description 1
• 229940030606 diuretics Drugs 0.000 description 1
• 229960001089 dobutamine Drugs 0.000 description 1
• 229960003638 dopamine Drugs 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 229960001389 doxazosin Drugs 0.000 description 1
• RUZYUOTYCVRMRZ-UHFFFAOYSA-N doxazosin Chemical compound C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 RUZYUOTYCVRMRZ-UHFFFAOYSA-N 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 229950006127 embusartan Drugs 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 208000028208 end stage renal disease Diseases 0.000 description 1
• 201000000523 end stage renal failure Diseases 0.000 description 1
• 108010030074 endodeoxyribonuclease MluI Proteins 0.000 description 1
• 230000008694 endothelial dysfunction Effects 0.000 description 1
• 230000008753 endothelial function Effects 0.000 description 1
• 239000003344 environmental pollutant Substances 0.000 description 1
• 208000001780 epistaxis Diseases 0.000 description 1
• 229960004563 eprosartan Drugs 0.000 description 1
• OROAFUQRIXKEMV-LDADJPATSA-N eprosartan Chemical compound C=1C=C(C(O)=O)C=CC=1CN1C(CCCC)=NC=C1\C=C(C(O)=O)/CC1=CC=CS1 OROAFUQRIXKEMV-LDADJPATSA-N 0.000 description 1
• 210000003743 erythrocyte Anatomy 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
• 238000000605 extraction Methods 0.000 description 1
• 229940012413 factor vii Drugs 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 239000010685 fatty oil Substances 0.000 description 1
• 210000001105 femoral artery Anatomy 0.000 description 1
• 210000003191 femoral vein Anatomy 0.000 description 1
• 230000003480 fibrinolytic effect Effects 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• AAXVEMMRQDVLJB-BULBTXNYSA-N fludrocortisone Chemical compound O=C1CC[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 AAXVEMMRQDVLJB-BULBTXNYSA-N 0.000 description 1
• 229960002011 fludrocortisone Drugs 0.000 description 1
• 229960003765 fluvastatin Drugs 0.000 description 1
• 229960002490 fosinopril Drugs 0.000 description 1
• 239000004023 fresh frozen plasma Substances 0.000 description 1
• 239000012737 fresh medium Substances 0.000 description 1
• 229960003883 furosemide Drugs 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
• 239000000499 gel Substances 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 210000004602 germ cell Anatomy 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 1
• 230000013595 glycosylation Effects 0.000 description 1
• 238000006206 glycosylation reaction Methods 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 238000012835 hanging drop method Methods 0.000 description 1
• 230000035876 healing Effects 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 210000002216 heart Anatomy 0.000 description 1
• 210000003709 heart valve Anatomy 0.000 description 1
• 208000018578 heart valve disease Diseases 0.000 description 1
• 208000034737 hemoglobinopathy Diseases 0.000 description 1
• 208000007475 hemolytic anemia Diseases 0.000 description 1
• 230000002008 hemorrhagic effect Effects 0.000 description 1
• 239000002874 hemostatic agent Substances 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 239000002554 heparinoid Substances 0.000 description 1
• 229940025770 heparinoids Drugs 0.000 description 1
• 229940006607 hirudin Drugs 0.000 description 1
• WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 1
• 239000005556 hormone Substances 0.000 description 1
• 229940088597 hormone Drugs 0.000 description 1
• 210000004408 hybridoma Anatomy 0.000 description 1
• 229960002003 hydrochlorothiazide Drugs 0.000 description 1
• 229960000890 hydrocortisone Drugs 0.000 description 1
• 238000012872 hydroxylapatite chromatography Methods 0.000 description 1
• 208000000122 hyperventilation Diseases 0.000 description 1
• 230000000870 hyperventilation Effects 0.000 description 1
• 230000007954 hypoxia Effects 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 230000005847 immunogenicity Effects 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 230000007574 infarction Effects 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 230000000297 inotrophic effect Effects 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 229960002198 irbesartan Drugs 0.000 description 1
• YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
• NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 1
• 230000001788 irregular Effects 0.000 description 1
• 208000028867 ischemia Diseases 0.000 description 1
• FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
• 238000005304 joining Methods 0.000 description 1
• 229930027917 kanamycin Natural products 0.000 description 1
• 229960000318 kanamycin Drugs 0.000 description 1
• SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
• 229930182823 kanamycin A Natural products 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• VCMGMSHEPQENPE-UHFFFAOYSA-N ketamine hydrochloride Chemical compound [Cl-].C=1C=CC=C(Cl)C=1C1([NH2+]C)CCCCC1=O VCMGMSHEPQENPE-UHFFFAOYSA-N 0.000 description 1
• 201000006370 kidney failure Diseases 0.000 description 1
• 239000002523 lectin Substances 0.000 description 1
• 229940095570 lescol Drugs 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 231100000636 lethal dose Toxicity 0.000 description 1
• 150000002614 leucines Chemical group 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 229940002661 lipitor Drugs 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 238000009630 liquid culture Methods 0.000 description 1
• 229960002394 lisinopril Drugs 0.000 description 1
• RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 229960004773 losartan Drugs 0.000 description 1
• KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 1
• 229960004844 lovastatin Drugs 0.000 description 1
• QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
• 229940127215 low-molecular weight heparin Drugs 0.000 description 1
• 239000008176 lyophilized powder Substances 0.000 description 1
• 208000002780 macular degeneration Diseases 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 208000007106 menorrhagia Diseases 0.000 description 1
• 108020004999 messenger RNA Proteins 0.000 description 1
• 230000009401 metastasis Effects 0.000 description 1
• LYVGOAYMIAQLHI-UHFFFAOYSA-N methyl 2-butyl-1-[[2-fluoro-4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]-6-oxopyridine-4-carboxylate Chemical compound CCCCC1=CC(C(=O)OC)=CC(=O)N1CC1=CC=C(C=2C(=CC=CC=2)C2=NNN=N2)C=C1F LYVGOAYMIAQLHI-UHFFFAOYSA-N 0.000 description 1
• 229960002237 metoprolol Drugs 0.000 description 1
• IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 1
• 229940099246 mevacor Drugs 0.000 description 1
• 239000003607 modifier Substances 0.000 description 1
• 238000001823 molecular biology technique Methods 0.000 description 1
• 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
• 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
• 201000000050 myeloid neoplasm Diseases 0.000 description 1
• 229960004255 nadolol Drugs 0.000 description 1
• VWPOSFSPZNDTMJ-UCWKZMIHSA-N nadolol Chemical compound C1[C@@H](O)[C@@H](O)CC2=C1C=CC=C2OCC(O)CNC(C)(C)C VWPOSFSPZNDTMJ-UCWKZMIHSA-N 0.000 description 1
• 239000006225 natural substrate Substances 0.000 description 1
• 101150091879 neo gene Proteins 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
• 229960005425 nitrendipine Drugs 0.000 description 1
• 229910052757 nitrogen Inorganic materials 0.000 description 1
• 231100000956 nontoxicity Toxicity 0.000 description 1
• SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
• 229960002748 norepinephrine Drugs 0.000 description 1
• 238000007899 nucleic acid hybridization Methods 0.000 description 1
• 239000002751 oligonucleotide probe Substances 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 230000004768 organ dysfunction Effects 0.000 description 1
• 229940043515 other immunoglobulins in atc Drugs 0.000 description 1
• 238000004091 panning Methods 0.000 description 1
• 229940055729 papain Drugs 0.000 description 1
• 235000019834 papain Nutrition 0.000 description 1
• 244000045947 parasite Species 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 230000006320 pegylation Effects 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 229960002035 penbutolol Drugs 0.000 description 1
• KQXKVJAGOJTNJS-HNNXBMFYSA-N penbutolol Chemical compound CC(C)(C)NC[C@H](O)COC1=CC=CC=C1C1CCCC1 KQXKVJAGOJTNJS-HNNXBMFYSA-N 0.000 description 1
• 230000000149 penetrating effect Effects 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• 229940111202 pepsin Drugs 0.000 description 1
• 229960002582 perindopril Drugs 0.000 description 1
• IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 description 1
• 230000035699 permeability Effects 0.000 description 1
• 208000004594 persistent fetal circulation syndrome Diseases 0.000 description 1
• 229940080469 phosphocellulose Drugs 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 229960002508 pindolol Drugs 0.000 description 1
• PHUTUTUABXHXLW-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=NC=C[C]12 PHUTUTUABXHXLW-UHFFFAOYSA-N 0.000 description 1
• 229960001085 piretanide Drugs 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• 231100000719 pollutant Toxicity 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
• 239000013641 positive control Substances 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• 230000001323 posttranslational effect Effects 0.000 description 1
• 229940089484 pravachol Drugs 0.000 description 1
• 229960002965 pravastatin Drugs 0.000 description 1
• 229960001289 prazosin Drugs 0.000 description 1
• IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000003449 preventive effect Effects 0.000 description 1
• 238000011809 primate model Methods 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 230000001902 propagating effect Effects 0.000 description 1
• 229960003712 propranolol Drugs 0.000 description 1
• 235000019419 proteases Nutrition 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 229960000856 protein c Drugs 0.000 description 1
• 230000006916 protein interaction Effects 0.000 description 1
• 238000001742 protein purification Methods 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• 230000000541 pulsatile effect Effects 0.000 description 1
• 239000012264 purified product Substances 0.000 description 1
• ZLIBICFPKPWGIZ-UHFFFAOYSA-N pyrimethanil Chemical compound CC1=CC(C)=NC(NC=2C=CC=CC=2)=N1 ZLIBICFPKPWGIZ-UHFFFAOYSA-N 0.000 description 1
• 229960001455 quinapril Drugs 0.000 description 1
• JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 description 1
• 238000003127 radioimmunoassay Methods 0.000 description 1
• 238000011363 radioimmunotherapy Methods 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 229960003401 ramipril Drugs 0.000 description 1
• HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
• 230000008707 rearrangement Effects 0.000 description 1
• 238000003259 recombinant expression Methods 0.000 description 1
• 238000010188 recombinant method Methods 0.000 description 1
• 208000037803 restenosis Diseases 0.000 description 1
• 108091008146 restriction endonucleases Proteins 0.000 description 1
• 230000000717 retained effect Effects 0.000 description 1
• 229960002917 reteplase Drugs 0.000 description 1
• 108010051412 reteplase Proteins 0.000 description 1
• 230000033764 rhythmic process Effects 0.000 description 1
• 229940069575 rompun Drugs 0.000 description 1
• 150000003839 salts Chemical class 0.000 description 1
• 201000000306 sarcoidosis Diseases 0.000 description 1
• 229920006395 saturated elastomer Polymers 0.000 description 1
• 238000004626 scanning electron microscopy Methods 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 230000035939 shock Effects 0.000 description 1
• 229960002855 simvastatin Drugs 0.000 description 1
• 238000002741 site-directed mutagenesis Methods 0.000 description 1
• 201000002859 sleep apnea Diseases 0.000 description 1
• 230000000391 smoking effect Effects 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 230000002269 spontaneous effect Effects 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 238000003756 stirring Methods 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 229960005202 streptokinase Drugs 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 235000011149 sulphuric acid Nutrition 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• VCKUSRYTPJJLNI-UHFFFAOYSA-N terazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCCO1 VCKUSRYTPJJLNI-UHFFFAOYSA-N 0.000 description 1
• 229960001693 terazosin Drugs 0.000 description 1
• 231100001274 therapeutic index Toxicity 0.000 description 1
• 125000003396 thiol group Chemical group [H]S* 0.000 description 1
• 239000003634 thrombocyte concentrate Substances 0.000 description 1
• 229960000103 thrombolytic agent Drugs 0.000 description 1
• 229960004605 timolol Drugs 0.000 description 1
• 238000004448 titration Methods 0.000 description 1
• 229960005461 torasemide Drugs 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000002110 toxicologic effect Effects 0.000 description 1
• 231100000027 toxicology Toxicity 0.000 description 1
• 238000011830 transgenic mouse model Methods 0.000 description 1
• 238000013519 translation Methods 0.000 description 1
• 230000014621 translational initiation Effects 0.000 description 1
• 150000003626 triacylglycerols Chemical class 0.000 description 1
• 239000012588 trypsin Substances 0.000 description 1
• 238000010798 ubiquitination Methods 0.000 description 1
• 230000034512 ubiquitination Effects 0.000 description 1
• 241001515965 unidentified phage Species 0.000 description 1
• 210000002700 urine Anatomy 0.000 description 1
• 229960005356 urokinase Drugs 0.000 description 1
• 229960004699 valsartan Drugs 0.000 description 1
• SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 1
• 230000003966 vascular damage Effects 0.000 description 1
• 230000008728 vascular permeability Effects 0.000 description 1
• 230000000304 vasodilatating effect Effects 0.000 description 1
• 229960003726 vasopressin Drugs 0.000 description 1
• 210000003462 vein Anatomy 0.000 description 1
• 229960001722 verapamil Drugs 0.000 description 1
• 239000013603 viral vector Substances 0.000 description 1
• 108010047303 von Willebrand Factor Proteins 0.000 description 1
• 102100036537 von Willebrand factor Human genes 0.000 description 1
• 229960001134 von willebrand factor Drugs 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
• 229960001600 xylazine Drugs 0.000 description 1
• QYEFBJRXKKSABU-UHFFFAOYSA-N xylazine hydrochloride Chemical compound Cl.CC1=CC=CC(C)=C1NC1=NCCCS1 QYEFBJRXKKSABU-UHFFFAOYSA-N 0.000 description 1
• 229940072168 zocor Drugs 0.000 description 1