CA3070037A1 - Use of wx-uk1 and its prodrug, wx-671, for the treatment of non-cancerous medical conditions - Google Patents
Use of wx-uk1 and its prodrug, wx-671, for the treatment of non-cancerous medical conditions Download PDFInfo
- Publication number
- CA3070037A1 CA3070037A1 CA3070037A CA3070037A CA3070037A1 CA 3070037 A1 CA3070037 A1 CA 3070037A1 CA 3070037 A CA3070037 A CA 3070037A CA 3070037 A CA3070037 A CA 3070037A CA 3070037 A1 CA3070037 A1 CA 3070037A1
- Authority
- CA
- Canada
- Prior art keywords
- trypsin
- human
- animal
- compound
- irritable bowel
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 229940002612 prodrug Drugs 0.000 title description 30
- 239000000651 prodrug Substances 0.000 title description 30
- 150000001875 compounds Chemical class 0.000 claims abstract description 54
- 238000000034 method Methods 0.000 claims abstract description 47
- 241001465754 Metazoa Species 0.000 claims abstract description 46
- 102000004142 Trypsin Human genes 0.000 claims abstract description 40
- 108090000631 Trypsin Proteins 0.000 claims abstract description 40
- 239000012588 trypsin Substances 0.000 claims abstract description 40
- 208000002551 irritable bowel syndrome Diseases 0.000 claims abstract description 37
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
- 206010033645 Pancreatitis Diseases 0.000 claims abstract description 18
- 239000000523 sample Substances 0.000 claims abstract description 18
- 239000000203 mixture Substances 0.000 claims abstract description 17
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 16
- 239000012472 biological sample Substances 0.000 claims abstract description 15
- 238000012360 testing method Methods 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 239000003937 drug carrier Substances 0.000 claims abstract description 8
- 208000007882 Gastritis Diseases 0.000 claims abstract description 6
- 239000013078 crystal Substances 0.000 claims abstract description 6
- 239000002207 metabolite Substances 0.000 claims abstract description 6
- 241000282414 Homo sapiens Species 0.000 claims description 57
- 102100034396 Trypsin-3 Human genes 0.000 claims description 23
- 239000003814 drug Substances 0.000 claims description 20
- 101710119642 Trypsin-3 Proteins 0.000 claims description 15
- 102100034392 Trypsin-2 Human genes 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 12
- 101710119666 Trypsin-2 Proteins 0.000 claims description 9
- 210000002966 serum Anatomy 0.000 claims description 8
- 239000012530 fluid Substances 0.000 claims description 7
- 238000001574 biopsy Methods 0.000 claims description 6
- 230000002183 duodenal effect Effects 0.000 claims description 6
- 230000000968 intestinal effect Effects 0.000 claims description 6
- 210000004369 blood Anatomy 0.000 claims description 5
- 239000008280 blood Substances 0.000 claims description 5
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims description 5
- 206010033647 Pancreatitis acute Diseases 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 201000003229 acute pancreatitis Diseases 0.000 claims description 4
- 210000003296 saliva Anatomy 0.000 claims description 4
- 210000002700 urine Anatomy 0.000 claims description 4
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- 208000010643 digestive system disease Diseases 0.000 abstract description 8
- 239000002753 trypsin inhibitor Substances 0.000 abstract description 5
- 229940122618 Trypsin inhibitor Drugs 0.000 abstract description 3
- 101710162629 Trypsin inhibitor Proteins 0.000 abstract description 3
- 230000001668 ameliorated effect Effects 0.000 abstract description 2
- ISJSHQTWOHGCMM-NDEPHWFRSA-N ethyl 4-[(2s)-3-(3-carbamimidoylphenyl)-2-[[2,4,6-tri(propan-2-yl)phenyl]sulfonylamino]propanoyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C(=O)[C@@H](NS(=O)(=O)C=1C(=CC(=CC=1C(C)C)C(C)C)C(C)C)CC1=CC=CC(C(N)=N)=C1 ISJSHQTWOHGCMM-NDEPHWFRSA-N 0.000 description 136
- CYCFEEXTLQGJEL-XEOXDSMQSA-N ethyl 4-[(2s)-3-[3-[(e)-(hydroxyhydrazinylidene)methyl]phenyl]-2-[[2,4,6-tri(propan-2-yl)phenyl]sulfonylamino]propanoyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C(=O)[C@@H](NS(=O)(=O)C=1C(=CC(=CC=1C(C)C)C(C)C)C(C)C)CC1=CC=CC(\C=N\NO)=C1 CYCFEEXTLQGJEL-XEOXDSMQSA-N 0.000 description 41
- 102100037942 Suppressor of tumorigenicity 14 protein Human genes 0.000 description 35
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 25
- 108010091175 Matriptase Proteins 0.000 description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 24
- 201000010099 disease Diseases 0.000 description 22
- 230000000694 effects Effects 0.000 description 21
- 101000661807 Homo sapiens Suppressor of tumorigenicity 14 protein Proteins 0.000 description 18
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 18
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 18
- 239000003112 inhibitor Substances 0.000 description 17
- 101000847952 Homo sapiens Trypsin-3 Proteins 0.000 description 16
- 206010028980 Neoplasm Diseases 0.000 description 16
- 210000001519 tissue Anatomy 0.000 description 15
- 108010070503 PAR-2 Receptor Proteins 0.000 description 14
- 102000012479 Serine Proteases Human genes 0.000 description 14
- 108010022999 Serine Proteases Proteins 0.000 description 14
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 14
- 102000035195 Peptidases Human genes 0.000 description 13
- 108091005804 Peptidases Proteins 0.000 description 13
- 239000004365 Protease Substances 0.000 description 13
- 102000032628 PAR-2 Receptor Human genes 0.000 description 12
- 238000010494 dissociation reaction Methods 0.000 description 12
- 230000005593 dissociations Effects 0.000 description 12
- 230000003993 interaction Effects 0.000 description 12
- 102000004190 Enzymes Human genes 0.000 description 11
- 108090000790 Enzymes Proteins 0.000 description 11
- 101000848014 Homo sapiens Trypsin-2 Proteins 0.000 description 11
- 229940088598 enzyme Drugs 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 11
- 230000004913 activation Effects 0.000 description 10
- 239000002552 dosage form Substances 0.000 description 10
- 230000001225 therapeutic effect Effects 0.000 description 10
- 102000045851 human PRSS3 Human genes 0.000 description 9
- 239000003446 ligand Substances 0.000 description 9
- 101000655897 Homo sapiens Serine protease 1 Proteins 0.000 description 8
- 101000638886 Homo sapiens Urokinase-type plasminogen activator Proteins 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 102000051039 human ST14 Human genes 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- 102100032491 Serine protease 1 Human genes 0.000 description 7
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 7
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 7
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 102000048529 human PRSS1 Human genes 0.000 description 7
- 238000001802 infusion Methods 0.000 description 7
- 210000004072 lung Anatomy 0.000 description 7
- 210000000496 pancreas Anatomy 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 230000001810 trypsinlike Effects 0.000 description 7
- YKYIFUROKBDHCY-ONEGZZNKSA-N (e)-4-ethoxy-1,1,1-trifluorobut-3-en-2-one Chemical group CCO\C=C\C(=O)C(F)(F)F YKYIFUROKBDHCY-ONEGZZNKSA-N 0.000 description 6
- 208000019693 Lung disease Diseases 0.000 description 6
- 101710151387 Serine protease 1 Proteins 0.000 description 6
- 101710119665 Trypsin-1 Proteins 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- 208000006682 alpha 1-Antitrypsin Deficiency Diseases 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 102000043864 human PRSS2 Human genes 0.000 description 6
- 208000027866 inflammatory disease Diseases 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 208000004852 Lung Injury Diseases 0.000 description 5
- 206010069363 Traumatic lung injury Diseases 0.000 description 5
- 239000012491 analyte Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- 231100000515 lung injury Toxicity 0.000 description 5
- 201000001320 Atherosclerosis Diseases 0.000 description 4
- 241000283690 Bos taurus Species 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 229940122378 Trypsin-3 inhibitor Drugs 0.000 description 4
- 108010027252 Trypsinogen Proteins 0.000 description 4
- 102000018690 Trypsinogen Human genes 0.000 description 4
- 206010069351 acute lung injury Diseases 0.000 description 4
- 206010003230 arteritis Diseases 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 239000003593 chromogenic compound Substances 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 102000038379 digestive enzymes Human genes 0.000 description 4
- 108091007734 digestive enzymes Proteins 0.000 description 4
- 238000011065 in-situ storage Methods 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 210000000265 leukocyte Anatomy 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 235000019419 proteases Nutrition 0.000 description 4
- 230000002797 proteolythic effect Effects 0.000 description 4
- 230000002685 pulmonary effect Effects 0.000 description 4
- 239000012146 running buffer Substances 0.000 description 4
- 230000011664 signaling Effects 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 238000007805 zymography Methods 0.000 description 4
- 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 3
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000015271 coagulation Effects 0.000 description 3
- 238000005345 coagulation Methods 0.000 description 3
- 210000004953 colonic tissue Anatomy 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 3
- 229910052737 gold Inorganic materials 0.000 description 3
- 239000010931 gold Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 230000000770 proinflammatory effect Effects 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 208000017520 skin disease Diseases 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 230000003827 upregulation Effects 0.000 description 3
- AGWHIZUOJZPQQM-UHFFFAOYSA-N 4-amino-3-(trifluoromethyl)chromen-2-one Chemical compound C1=CC=CC2=C1OC(=O)C(C(F)(F)F)=C2N AGWHIZUOJZPQQM-UHFFFAOYSA-N 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
- 206010010774 Constipation Diseases 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 2
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 2
- 102000004890 Interleukin-8 Human genes 0.000 description 2
- 108090001007 Interleukin-8 Proteins 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 102000018402 Protease-activated receptor 2 Human genes 0.000 description 2
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 2
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 108091006629 SLC13A2 Proteins 0.000 description 2
- 229940122055 Serine protease inhibitor Drugs 0.000 description 2
- 101710102218 Serine protease inhibitor Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 239000002257 antimetastatic agent Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000012742 biochemical analysis Methods 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000000112 colonic effect Effects 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 230000001079 digestive effect Effects 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000005216 enteric neuron Anatomy 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 230000013632 homeostatic process Effects 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 238000012804 iterative process Methods 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000013037 reversible inhibitor Substances 0.000 description 2
- 210000001044 sensory neuron Anatomy 0.000 description 2
- 238000002864 sequence alignment Methods 0.000 description 2
- 239000003001 serine protease inhibitor Substances 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 108010036927 trypsin-like serine protease Proteins 0.000 description 2
- 230000007306 turnover Effects 0.000 description 2
- 210000005166 vasculature Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 101710105313 Anionic trypsin Proteins 0.000 description 1
- 101000655894 Bos taurus Serine protease 1 Proteins 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 102100029727 Enteropeptidase Human genes 0.000 description 1
- 108010013369 Enteropeptidase Proteins 0.000 description 1
- 239000009484 FIBS Substances 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 208000014540 Functional gastrointestinal disease Diseases 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010043026 HGF activator Proteins 0.000 description 1
- 102100031465 Hepatocyte growth factor activator Human genes 0.000 description 1
- 101000823116 Homo sapiens Alpha-1-antitrypsin Proteins 0.000 description 1
- 101000856199 Homo sapiens Chymotrypsin-like protease CTRL-1 Proteins 0.000 description 1
- 101000966403 Homo sapiens Dynein light chain 1, cytoplasmic Proteins 0.000 description 1
- 101001066338 Homo sapiens Hepatocyte growth factor activator Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 206010024404 Leukostasis Diseases 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101000638885 Mus musculus Urokinase-type plasminogen activator Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000007920 Neurogenic Inflammation Diseases 0.000 description 1
- 240000008881 Oenanthe javanica Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000008080 Pancreatitis-Associated Proteins Human genes 0.000 description 1
- 108010074467 Pancreatitis-Associated Proteins Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 101800004937 Protein C Proteins 0.000 description 1
- 102000017975 Protein C Human genes 0.000 description 1
- 241000350481 Pterogyne nitens Species 0.000 description 1
- 101000749632 Rattus norvegicus Urokinase-type plasminogen activator Proteins 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 101800001700 Saposin-D Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 208000024248 Vascular System injury Diseases 0.000 description 1
- 208000012339 Vascular injury Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000037365 barrier function of the epidermis Effects 0.000 description 1
- 238000007622 bioinformatic analysis Methods 0.000 description 1
- 238000003766 bioinformatics method Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 239000002772 conduction electron Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 230000007360 epithelial dysfunction Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000006624 extrinsic pathway Effects 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 102000054833 human CTRL Human genes 0.000 description 1
- 102000047519 human DYNLL1 Human genes 0.000 description 1
- 102000051631 human SERPINA1 Human genes 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 210000002490 intestinal epithelial cell Anatomy 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 238000002032 lab-on-a-chip Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 108010047374 matriptase 2 Proteins 0.000 description 1
- 239000002082 metal nanoparticle Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000004089 microcirculation Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004001 molecular interaction Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- UPSFMJHZUCSEHU-JYGUBCOQSA-N n-[(2s,3r,4r,5s,6r)-2-[(2r,3s,4r,5r,6s)-5-acetamido-4-hydroxy-2-(hydroxymethyl)-6-(4-methyl-2-oxochromen-7-yl)oxyoxan-3-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide Chemical compound CC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@H](O)[C@@H](NC(C)=O)[C@H](OC=2C=C3OC(=O)C=C(C)C3=CC=2)O[C@@H]1CO UPSFMJHZUCSEHU-JYGUBCOQSA-N 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 210000004798 organs belonging to the digestive system Anatomy 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 231100000255 pathogenic effect Toxicity 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229940012957 plasmin Drugs 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 108010031970 prostasin Proteins 0.000 description 1
- 229960000856 protein c Drugs 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 230000008591 skin barrier function Effects 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229960003766 thrombin (human) Drugs 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000029534 trypsinogen activation Effects 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 229950008529 upamostat Drugs 0.000 description 1
- 210000002438 upper gastrointestinal tract Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/914—Hydrolases (3)
- G01N2333/948—Hydrolases (3) acting on peptide bonds (3.4)
- G01N2333/95—Proteinases, i.e. endopeptidases (3.4.21-3.4.99)
- G01N2333/964—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue
- G01N2333/96425—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals
- G01N2333/96427—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general
- G01N2333/9643—Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general with EC number
- G01N2333/96433—Serine endopeptidases (3.4.21)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/914—Hydrolases (3)
- G01N2333/948—Hydrolases (3) acting on peptide bonds (3.4)
- G01N2333/976—Trypsin; Chymotrypsin
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Cell Biology (AREA)
- Pathology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- General Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Food Science & Technology (AREA)
- Physiology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Nutrition Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762535376P | 2017-07-21 | 2017-07-21 | |
| US62/535,376 | 2017-07-21 | ||
| US201762574449P | 2017-10-19 | 2017-10-19 | |
| US62/574,449 | 2017-10-19 | ||
| US201762589734P | 2017-11-22 | 2017-11-22 | |
| US62/589,734 | 2017-11-22 | ||
| PCT/IB2018/000881 WO2019016595A1 (en) | 2017-07-21 | 2018-07-13 | USE OF WX-UK1 AND ITS PRODRANT WX-671 FOR THE TREATMENT OF NON-CANCER MEDICAL DISEASES |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3070037A1 true CA3070037A1 (en) | 2019-01-24 |
Family
ID=65014605
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3070037A Abandoned CA3070037A1 (en) | 2017-07-21 | 2018-07-13 | Use of wx-uk1 and its prodrug, wx-671, for the treatment of non-cancerous medical conditions |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US20190022088A1 (https=) |
| EP (1) | EP3654979A4 (https=) |
| JP (1) | JP2020527582A (https=) |
| KR (1) | KR20200031567A (https=) |
| CN (1) | CN110785172A (https=) |
| AU (1) | AU2018303799A1 (https=) |
| CA (1) | CA3070037A1 (https=) |
| CL (1) | CL2020000096A1 (https=) |
| IL (1) | IL271878A (https=) |
| PH (1) | PH12019502817A1 (https=) |
| RU (1) | RU2020107706A (https=) |
| SG (1) | SG11201912043QA (https=) |
| WO (1) | WO2019016595A1 (https=) |
| ZA (1) | ZA201908545B (https=) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111494602B (zh) * | 2020-04-14 | 2023-06-02 | 广州领晟医疗科技有限公司 | 一种治疗急性胰腺炎的组合物及其用途 |
| CN111494392A (zh) * | 2020-04-14 | 2020-08-07 | 广州领晟医疗科技有限公司 | 一种用于治疗急性肺损伤的组合物及其应用 |
| CN113559100B (zh) * | 2021-08-30 | 2023-01-17 | 广州领晟医疗科技有限公司 | 一种治疗肺损伤的组合物及其应用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5534498A (en) * | 1992-01-30 | 1996-07-09 | Corvas International, Inc. | Trypsin inhibitors |
| US7342018B2 (en) * | 1998-07-20 | 2008-03-11 | Wilex Ag | Urokinase inhibitors and uses thereof |
| AU2003206945A1 (en) * | 2002-02-22 | 2003-09-09 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Use of proteinase inhibitors in the treatment of autoimmune diseases |
| DE10323898A1 (de) * | 2003-05-26 | 2004-12-23 | Wilex Ag | Hydroxyamidin- und Hydroxyguanidin-Verbindungen als Urokinase-Hemmstoffe |
| EP3309556B1 (en) * | 2009-06-25 | 2020-04-08 | Prometheus Biosciences, Inc. | Methods for diagnosing irritable bowel syndrome |
-
2018
- 2018-07-13 WO PCT/IB2018/000881 patent/WO2019016595A1/en not_active Ceased
- 2018-07-13 EP EP18835233.0A patent/EP3654979A4/en not_active Withdrawn
- 2018-07-13 SG SG11201912043QA patent/SG11201912043QA/en unknown
- 2018-07-13 KR KR1020197037453A patent/KR20200031567A/ko not_active Ceased
- 2018-07-13 CA CA3070037A patent/CA3070037A1/en not_active Abandoned
- 2018-07-13 US US16/034,815 patent/US20190022088A1/en not_active Abandoned
- 2018-07-13 RU RU2020107706A patent/RU2020107706A/ru not_active Application Discontinuation
- 2018-07-13 JP JP2020502586A patent/JP2020527582A/ja active Pending
- 2018-07-13 CN CN201880042082.2A patent/CN110785172A/zh active Pending
- 2018-07-13 AU AU2018303799A patent/AU2018303799A1/en not_active Abandoned
-
2019
- 2019-12-13 PH PH12019502817A patent/PH12019502817A1/en unknown
- 2019-12-20 ZA ZA2019/08545A patent/ZA201908545B/en unknown
-
2020
- 2020-01-07 IL IL271878A patent/IL271878A/en unknown
- 2020-01-13 CL CL2020000096A patent/CL2020000096A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SG11201912043QA (en) | 2020-02-27 |
| EP3654979A4 (en) | 2021-04-14 |
| RU2020107706A (ru) | 2021-08-23 |
| CN110785172A (zh) | 2020-02-11 |
| JP2020527582A (ja) | 2020-09-10 |
| CL2020000096A1 (es) | 2020-08-28 |
| PH12019502817A1 (en) | 2020-09-14 |
| RU2020107706A3 (https=) | 2021-10-15 |
| US20190022088A1 (en) | 2019-01-24 |
| AU2018303799A1 (en) | 2019-12-19 |
| IL271878A (en) | 2020-02-27 |
| ZA201908545B (en) | 2021-02-24 |
| WO2019016595A1 (en) | 2019-01-24 |
| EP3654979A1 (en) | 2020-05-27 |
| KR20200031567A (ko) | 2020-03-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wettstein et al. | The transmembrane protease TMPRSS2 as a therapeutic target for COVID-19 treatment | |
| Shrimp et al. | An enzymatic TMPRSS2 assay for assessment of clinical candidates and discovery of inhibitors as potential treatment of COVID-19 | |
| Amin et al. | Design of aminopeptidase N inhibitors as anti-cancer agents | |
| Bua et al. | Design and synthesis of novel nonsteroidal anti-inflammatory drugs and carbonic anhydrase inhibitors hybrids (NSAIDs–CAIs) for the treatment of rheumatoid arthritis | |
| ES2828985T3 (es) | Detección basada en la afinidad de biomarcadores sintéticos codificados por ligando | |
| Guay et al. | Therapeutic utility and medicinal chemistry of cathepsin C inhibitors | |
| Baggio et al. | Therapeutic targeting of MMP-12 for the treatment of chronic obstructive pulmonary disease | |
| US11771710B2 (en) | Method to treat lipid dysregulation by modulation of proprotein convertase subtilisin/kexin type 9 (PCSK9) protein activity with small molecule ligands | |
| Bordenave et al. | Synthesis and in vitro and in vivo evaluation of MMP-12 selective optical probes | |
| US20190022088A1 (en) | Use of wx-uk1 and its prodrug, wx-671, for the treatment of non-cancerous medical conditions | |
| Qiu et al. | Exploration of janus kinase (JAK) and histone deacetylase (HDAC) bispecific inhibitors based on the moiety of fedratinib for treatment of both hematologic malignancies and solid cancers | |
| US20210215714A1 (en) | Complement alternative pathway-associated nephropathy biomarkers | |
| US10336827B2 (en) | Compositions and methods to treat solid tumors | |
| CN118580340B (zh) | 一种抗凝多肽及其在制备血浆激肽释放酶活性抑制剂中的应用 | |
| Takeuchi et al. | Discovery of aryloxyphenyl–heptapeptide hybrids as potent and selective matrix metalloproteinase-2 inhibitors for the treatment of idiopathic pulmonary fibrosis | |
| Hinkes et al. | Optimization of cyclic plasmin inhibitors: from benzamidines to benzylamines | |
| CN117164666A (zh) | 一种抗凝血多肽le6及其应用 | |
| EP1355637A2 (en) | Inhibitors of matriptase for the treatment of cancer | |
| US6677377B2 (en) | Structure based discovery of inhibitors of matriptase for the treatment of cancer and other conditions | |
| Kirchhain et al. | Biphenyl substituted lysine derivatives as recognition elements for the matrix metalloproteinases MMP-2 and MMP-9 | |
| Tabuse et al. | Discovery of Highly Potent and Selective Matrix Metalloproteinase-7 Inhibitors by Hybridizing the S1′ Subsite Binder with Short Peptides | |
| ES2627281T3 (es) | Derivados del ácido carboxílico sustituidos como agregados agrecanasa para el tratamiento de la artrosis | |
| CA2963684A1 (en) | Isoform-specific calpain inhibitors, methods of identification, and uses thereof | |
| EP2353599A1 (en) | 8-hydroxyquinolines as inhibitors of cathepsin B | |
| ES2919898A1 (es) | Nuevo tratamiento del cáncer colorrectal |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20240115 |