JP2018511616A - 短鎖デヒドロゲナーゼ活性を調節する組成物および方法 - Google Patents
短鎖デヒドロゲナーゼ活性を調節する組成物および方法 Download PDFInfo
- Publication number
- JP2018511616A JP2018511616A JP2017553122A JP2017553122A JP2018511616A JP 2018511616 A JP2018511616 A JP 2018511616A JP 2017553122 A JP2017553122 A JP 2017553122A JP 2017553122 A JP2017553122 A JP 2017553122A JP 2018511616 A JP2018511616 A JP 2018511616A
- Authority
- JP
- Japan
- Prior art keywords
- subject
- inhibitor
- disease
- alkyl
- administered
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 91
- 230000000694 effects Effects 0.000 title claims abstract description 42
- 239000000203 mixture Substances 0.000 title claims description 66
- 102000009105 Short Chain Dehydrogenase-Reductases Human genes 0.000 title claims description 21
- 108010048287 Short Chain Dehydrogenase-Reductases Proteins 0.000 title claims description 21
- 239000003112 inhibitor Substances 0.000 claims abstract description 245
- 108010051913 15-hydroxyprostaglandin dehydrogenase Proteins 0.000 claims abstract description 238
- 102100030489 15-hydroxyprostaglandin dehydrogenase [NAD(+)] Human genes 0.000 claims abstract description 235
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 126
- 150000001875 compounds Chemical class 0.000 claims abstract description 93
- 201000010099 disease Diseases 0.000 claims abstract description 63
- 208000035475 disorder Diseases 0.000 claims abstract description 62
- 150000003180 prostaglandins Chemical class 0.000 claims abstract description 42
- -1 R 21 Chemical compound 0.000 claims description 153
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 141
- 125000000217 alkyl group Chemical group 0.000 claims description 129
- 210000001519 tissue Anatomy 0.000 claims description 124
- 210000001185 bone marrow Anatomy 0.000 claims description 93
- 210000000130 stem cell Anatomy 0.000 claims description 89
- 125000003118 aryl group Chemical group 0.000 claims description 88
- 230000000302 ischemic effect Effects 0.000 claims description 62
- 206010016654 Fibrosis Diseases 0.000 claims description 56
- 229910052757 nitrogen Inorganic materials 0.000 claims description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims description 52
- 208000028867 ischemia Diseases 0.000 claims description 47
- 238000002512 chemotherapy Methods 0.000 claims description 46
- 210000000056 organ Anatomy 0.000 claims description 46
- 239000001257 hydrogen Substances 0.000 claims description 44
- 238000011282 treatment Methods 0.000 claims description 43
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 41
- 239000003814 drug Substances 0.000 claims description 40
- 210000004700 fetal blood Anatomy 0.000 claims description 40
- 230000001965 increasing effect Effects 0.000 claims description 40
- 238000002360 preparation method Methods 0.000 claims description 40
- 230000004761 fibrosis Effects 0.000 claims description 38
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 38
- 230000001225 therapeutic effect Effects 0.000 claims description 38
- 208000007502 anemia Diseases 0.000 claims description 37
- 238000002054 transplantation Methods 0.000 claims description 36
- 229940079593 drug Drugs 0.000 claims description 35
- 125000006413 ring segment Chemical group 0.000 claims description 35
- 208000027418 Wounds and injury Diseases 0.000 claims description 32
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 31
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 29
- 230000003176 fibrotic effect Effects 0.000 claims description 29
- 238000001959 radiotherapy Methods 0.000 claims description 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 28
- 230000006378 damage Effects 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 28
- 125000000623 heterocyclic group Chemical group 0.000 claims description 27
- 125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 27
- 206010028980 Neoplasm Diseases 0.000 claims description 26
- 125000003342 alkenyl group Chemical group 0.000 claims description 26
- 210000004185 liver Anatomy 0.000 claims description 26
- 210000004369 blood Anatomy 0.000 claims description 25
- 239000008280 blood Substances 0.000 claims description 25
- 208000004235 neutropenia Diseases 0.000 claims description 25
- 206010043554 thrombocytopenia Diseases 0.000 claims description 25
- 102000004127 Cytokines Human genes 0.000 claims description 24
- 108090000695 Cytokines Proteins 0.000 claims description 24
- 206010061218 Inflammation Diseases 0.000 claims description 24
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 24
- 230000004054 inflammatory process Effects 0.000 claims description 24
- 210000000440 neutrophil Anatomy 0.000 claims description 24
- 201000006474 Brain Ischemia Diseases 0.000 claims description 23
- 210000005259 peripheral blood Anatomy 0.000 claims description 23
- 239000011886 peripheral blood Substances 0.000 claims description 23
- 108090000623 proteins and genes Proteins 0.000 claims description 23
- 125000004414 alkyl thio group Chemical group 0.000 claims description 22
- 125000000304 alkynyl group Chemical group 0.000 claims description 22
- 206010008118 cerebral infarction Diseases 0.000 claims description 22
- 206010028537 myelofibrosis Diseases 0.000 claims description 22
- 208000024891 symptom Diseases 0.000 claims description 22
- 206010052428 Wound Diseases 0.000 claims description 21
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 208000031225 myocardial ischemia Diseases 0.000 claims description 21
- 229910052760 oxygen Inorganic materials 0.000 claims description 21
- 102000008186 Collagen Human genes 0.000 claims description 20
- 108010035532 Collagen Proteins 0.000 claims description 20
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 20
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 20
- 229920001436 collagen Polymers 0.000 claims description 20
- 229910052717 sulfur Inorganic materials 0.000 claims description 20
- 208000032467 Aplastic anaemia Diseases 0.000 claims description 19
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 19
- 230000007882 cirrhosis Effects 0.000 claims description 19
- 206010012601 diabetes mellitus Diseases 0.000 claims description 19
- 230000035876 healing Effects 0.000 claims description 19
- 208000005764 Peripheral Arterial Disease Diseases 0.000 claims description 18
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims description 18
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
- 230000017423 tissue regeneration Effects 0.000 claims description 18
- 210000003743 erythrocyte Anatomy 0.000 claims description 17
- 210000003734 kidney Anatomy 0.000 claims description 17
- 239000000126 substance Substances 0.000 claims description 17
- 229940124530 sulfonamide Drugs 0.000 claims description 17
- 150000003456 sulfonamides Chemical class 0.000 claims description 17
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 16
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims description 16
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims description 16
- 229910019142 PO4 Inorganic materials 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 201000011510 cancer Diseases 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 208000029078 coronary artery disease Diseases 0.000 claims description 16
- 230000014509 gene expression Effects 0.000 claims description 16
- 230000003394 haemopoietic effect Effects 0.000 claims description 16
- 230000001483 mobilizing effect Effects 0.000 claims description 16
- 239000010452 phosphate Substances 0.000 claims description 16
- 208000019553 vascular disease Diseases 0.000 claims description 16
- 208000010392 Bone Fractures Diseases 0.000 claims description 15
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 15
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 15
- 206010017076 Fracture Diseases 0.000 claims description 15
- 206010033661 Pancytopenia Diseases 0.000 claims description 15
- 208000036142 Viral infection Diseases 0.000 claims description 15
- 230000015572 biosynthetic process Effects 0.000 claims description 15
- 210000000988 bone and bone Anatomy 0.000 claims description 15
- 208000024389 cytopenia Diseases 0.000 claims description 15
- 230000003111 delayed effect Effects 0.000 claims description 15
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 15
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 102000004169 proteins and genes Human genes 0.000 claims description 15
- 230000004083 survival effect Effects 0.000 claims description 15
- 230000009385 viral infection Effects 0.000 claims description 15
- 230000029663 wound healing Effects 0.000 claims description 15
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 14
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 14
- 230000008021 deposition Effects 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 230000005855 radiation Effects 0.000 claims description 14
- 208000011580 syndromic disease Diseases 0.000 claims description 14
- 231100000331 toxic Toxicity 0.000 claims description 14
- 230000002588 toxic effect Effects 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 13
- 102000001554 Hemoglobins Human genes 0.000 claims description 13
- 108010054147 Hemoglobins Proteins 0.000 claims description 13
- 208000018262 Peripheral vascular disease Diseases 0.000 claims description 13
- 206010069351 acute lung injury Diseases 0.000 claims description 13
- 230000002401 inhibitory effect Effects 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- 208000006011 Stroke Diseases 0.000 claims description 12
- 206010000891 acute myocardial infarction Diseases 0.000 claims description 12
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
- 125000003282 alkyl amino group Chemical group 0.000 claims description 12
- 125000005110 aryl thio group Chemical group 0.000 claims description 12
- 210000001772 blood platelet Anatomy 0.000 claims description 12
- 238000005534 hematocrit Methods 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 12
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 12
- 238000001356 surgical procedure Methods 0.000 claims description 12
- 230000009885 systemic effect Effects 0.000 claims description 12
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 11
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 11
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 11
- 125000001769 aryl amino group Chemical group 0.000 claims description 11
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 11
- 238000002650 immunosuppressive therapy Methods 0.000 claims description 11
- 208000014674 injury Diseases 0.000 claims description 11
- 210000000936 intestine Anatomy 0.000 claims description 11
- 208000017169 kidney disease Diseases 0.000 claims description 11
- 239000000463 material Substances 0.000 claims description 11
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 11
- ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 claims description 11
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 11
- 239000007787 solid Substances 0.000 claims description 11
- 229930192474 thiophene Natural products 0.000 claims description 11
- 231100000419 toxicity Toxicity 0.000 claims description 11
- 230000001988 toxicity Effects 0.000 claims description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 10
- 206010039710 Scleroderma Diseases 0.000 claims description 10
- 230000002159 abnormal effect Effects 0.000 claims description 10
- 208000015322 bone marrow disease Diseases 0.000 claims description 10
- 239000004202 carbamide Substances 0.000 claims description 10
- 235000013877 carbamide Nutrition 0.000 claims description 10
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 10
- 208000015181 infectious disease Diseases 0.000 claims description 10
- 230000001665 lethal effect Effects 0.000 claims description 10
- 201000002793 renal fibrosis Diseases 0.000 claims description 10
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 10
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 9
- 208000011231 Crohn disease Diseases 0.000 claims description 9
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 9
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 9
- 206010019280 Heart failures Diseases 0.000 claims description 9
- 206010022680 Intestinal ischaemia Diseases 0.000 claims description 9
- 208000001132 Osteoporosis Diseases 0.000 claims description 9
- 206010063897 Renal ischaemia Diseases 0.000 claims description 9
- 201000009594 Systemic Scleroderma Diseases 0.000 claims description 9
- 206010042953 Systemic sclerosis Diseases 0.000 claims description 9
- 206010043540 Thromboangiitis obliterans Diseases 0.000 claims description 9
- 230000035508 accumulation Effects 0.000 claims description 9
- 238000009825 accumulation Methods 0.000 claims description 9
- 125000002252 acyl group Chemical group 0.000 claims description 9
- 125000004423 acyloxy group Chemical group 0.000 claims description 9
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 9
- 125000005277 alkyl imino group Chemical group 0.000 claims description 9
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 9
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 9
- 125000005116 aryl carbamoyl group Chemical group 0.000 claims description 9
- 125000004467 aryl imino group Chemical group 0.000 claims description 9
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 9
- 125000005163 aryl sulfanyl group Chemical group 0.000 claims description 9
- 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 9
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 9
- 125000004104 aryloxy group Chemical group 0.000 claims description 9
- 208000006673 asthma Diseases 0.000 claims description 9
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 9
- 238000004820 blood count Methods 0.000 claims description 9
- 210000002808 connective tissue Anatomy 0.000 claims description 9
- 210000003414 extremity Anatomy 0.000 claims description 9
- 238000011134 hematopoietic stem cell transplantation Methods 0.000 claims description 9
- 230000002757 inflammatory effect Effects 0.000 claims description 9
- 125000001261 isocyanato group Chemical group *N=C=O 0.000 claims description 9
- 125000002462 isocyano group Chemical group *[N+]#[C-] 0.000 claims description 9
- 125000001810 isothiocyanato group Chemical group *N=C=S 0.000 claims description 9
- RIFHJAODNHLCBH-UHFFFAOYSA-N methanethione Chemical group S=[CH] RIFHJAODNHLCBH-UHFFFAOYSA-N 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 9
- FVZVCSNXTFCBQU-UHFFFAOYSA-N phosphanyl Chemical group [PH2] FVZVCSNXTFCBQU-UHFFFAOYSA-N 0.000 claims description 9
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims description 9
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 9
- 230000002792 vascular Effects 0.000 claims description 9
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 8
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 claims description 8
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 claims description 8
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 206010021143 Hypoxia Diseases 0.000 claims description 8
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 8
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 8
- 208000025865 Ulcer Diseases 0.000 claims description 8
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 8
- 150000001413 amino acids Chemical class 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 208000020832 chronic kidney disease Diseases 0.000 claims description 8
- 206010009887 colitis Diseases 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 206010061989 glomerulosclerosis Diseases 0.000 claims description 8
- 208000024908 graft versus host disease Diseases 0.000 claims description 8
- 210000004969 inflammatory cell Anatomy 0.000 claims description 8
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 8
- 238000012261 overproduction Methods 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 210000002826 placenta Anatomy 0.000 claims description 8
- 230000002685 pulmonary effect Effects 0.000 claims description 8
- 238000007634 remodeling Methods 0.000 claims description 8
- 210000003954 umbilical cord Anatomy 0.000 claims description 8
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 7
- 206010040943 Skin Ulcer Diseases 0.000 claims description 7
- 206010052779 Transplant rejections Diseases 0.000 claims description 7
- 210000002744 extracellular matrix Anatomy 0.000 claims description 7
- 230000003779 hair growth Effects 0.000 claims description 7
- 230000007954 hypoxia Effects 0.000 claims description 7
- 208000030175 lameness Diseases 0.000 claims description 7
- 239000011159 matrix material Substances 0.000 claims description 7
- 231100000019 skin ulcer Toxicity 0.000 claims description 7
- 150000003577 thiophenes Chemical class 0.000 claims description 7
- 231100000397 ulcer Toxicity 0.000 claims description 7
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 6
- 208000004476 Acute Coronary Syndrome Diseases 0.000 claims description 6
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 6
- 201000004384 Alopecia Diseases 0.000 claims description 6
- 208000031104 Arterial Occlusive disease Diseases 0.000 claims description 6
- 208000033116 Asbestos intoxication Diseases 0.000 claims description 6
- 208000023275 Autoimmune disease Diseases 0.000 claims description 6
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 6
- 208000033222 Biliary cirrhosis primary Diseases 0.000 claims description 6
- 208000017234 Bone cyst Diseases 0.000 claims description 6
- 208000014644 Brain disease Diseases 0.000 claims description 6
- 206010048962 Brain oedema Diseases 0.000 claims description 6
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 6
- 206010007710 Cartilage injury Diseases 0.000 claims description 6
- 206010061762 Chondropathy Diseases 0.000 claims description 6
- 208000034656 Contusions Diseases 0.000 claims description 6
- 206010051055 Deep vein thrombosis Diseases 0.000 claims description 6
- 206010073306 Exposure to radiation Diseases 0.000 claims description 6
- 206010058490 Hyperoxia Diseases 0.000 claims description 6
- 206010022562 Intermittent claudication Diseases 0.000 claims description 6
- 208000029523 Interstitial Lung disease Diseases 0.000 claims description 6
- 208000034693 Laceration Diseases 0.000 claims description 6
- 206010028594 Myocardial fibrosis Diseases 0.000 claims description 6
- 208000018737 Parkinson disease Diseases 0.000 claims description 6
- 206010034576 Peripheral ischaemia Diseases 0.000 claims description 6
- 208000037581 Persistent Infection Diseases 0.000 claims description 6
- 208000012654 Primary biliary cholangitis Diseases 0.000 claims description 6
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 6
- 206010037423 Pulmonary oedema Diseases 0.000 claims description 6
- 206010063837 Reperfusion injury Diseases 0.000 claims description 6
- 208000017442 Retinal disease Diseases 0.000 claims description 6
- 206010038923 Retinopathy Diseases 0.000 claims description 6
- 206010040047 Sepsis Diseases 0.000 claims description 6
- 201000010001 Silicosis Diseases 0.000 claims description 6
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 claims description 6
- 208000007536 Thrombosis Diseases 0.000 claims description 6
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 6
- 206010047249 Venous thrombosis Diseases 0.000 claims description 6
- 241000700605 Viruses Species 0.000 claims description 6
- 239000000556 agonist Substances 0.000 claims description 6
- 208000021328 arterial occlusion Diseases 0.000 claims description 6
- 206010003441 asbestosis Diseases 0.000 claims description 6
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 claims description 6
- 208000006752 brain edema Diseases 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 150000007942 carboxylates Chemical class 0.000 claims description 6
- 125000002579 carboxylato group Chemical group [O-]C(*)=O 0.000 claims description 6
- 230000009787 cardiac fibrosis Effects 0.000 claims description 6
- 201000005483 chronic intestinal vascular insufficiency Diseases 0.000 claims description 6
- 230000009519 contusion Effects 0.000 claims description 6
- 210000004351 coronary vessel Anatomy 0.000 claims description 6
- 125000001651 cyanato group Chemical group [*]OC#N 0.000 claims description 6
- 239000000428 dust Substances 0.000 claims description 6
- 230000003073 embolic effect Effects 0.000 claims description 6
- 150000002170 ethers Chemical class 0.000 claims description 6
- 208000005017 glioblastoma Diseases 0.000 claims description 6
- 230000000222 hyperoxic effect Effects 0.000 claims description 6
- 239000007943 implant Substances 0.000 claims description 6
- 208000027866 inflammatory disease Diseases 0.000 claims description 6
- 208000021156 intermittent vascular claudication Diseases 0.000 claims description 6
- 230000003902 lesion Effects 0.000 claims description 6
- 210000003141 lower extremity Anatomy 0.000 claims description 6
- 230000001404 mediated effect Effects 0.000 claims description 6
- 208000010125 myocardial infarction Diseases 0.000 claims description 6
- 201000001119 neuropathy Diseases 0.000 claims description 6
- 230000007823 neuropathy Effects 0.000 claims description 6
- 201000008482 osteoarthritis Diseases 0.000 claims description 6
- 201000008968 osteosarcoma Diseases 0.000 claims description 6
- 206010035653 pneumoconiosis Diseases 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- 238000011084 recovery Methods 0.000 claims description 6
- 230000008929 regeneration Effects 0.000 claims description 6
- 238000011069 regeneration method Methods 0.000 claims description 6
- 208000032253 retinal ischemia Diseases 0.000 claims description 6
- 208000020431 spinal cord injury Diseases 0.000 claims description 6
- 210000002435 tendon Anatomy 0.000 claims description 6
- 230000001732 thrombotic effect Effects 0.000 claims description 6
- 208000037816 tissue injury Diseases 0.000 claims description 6
- 230000009529 traumatic brain injury Effects 0.000 claims description 6
- 208000006542 von Hippel-Lindau disease Diseases 0.000 claims description 6
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 5
- 208000022309 Alcoholic Liver disease Diseases 0.000 claims description 5
- 201000001320 Atherosclerosis Diseases 0.000 claims description 5
- 206010065384 Cerebral hypoperfusion Diseases 0.000 claims description 5
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 claims description 5
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 5
- 208000012641 Pigmentation disease Diseases 0.000 claims description 5
- 230000001154 acute effect Effects 0.000 claims description 5
- 230000017531 blood circulation Effects 0.000 claims description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
- 230000002255 enzymatic effect Effects 0.000 claims description 5
- 239000003102 growth factor Substances 0.000 claims description 5
- 201000002818 limb ischemia Diseases 0.000 claims description 5
- 208000019423 liver disease Diseases 0.000 claims description 5
- 210000003205 muscle Anatomy 0.000 claims description 5
- 150000003014 phosphoric acid esters Chemical class 0.000 claims description 5
- 230000000750 progressive effect Effects 0.000 claims description 5
- 230000035755 proliferation Effects 0.000 claims description 5
- 208000005333 pulmonary edema Diseases 0.000 claims description 5
- 230000004044 response Effects 0.000 claims description 5
- 229940126460 thrombopoietin receptor agonist Drugs 0.000 claims description 5
- 239000003053 toxin Substances 0.000 claims description 5
- 231100000765 toxin Toxicity 0.000 claims description 5
- 108700012359 toxins Proteins 0.000 claims description 5
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 4
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 4
- 206010053138 Congenital aplastic anaemia Diseases 0.000 claims description 4
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 108090001005 Interleukin-6 Proteins 0.000 claims description 4
- 102000004889 Interleukin-6 Human genes 0.000 claims description 4
- 206010025327 Lymphopenia Diseases 0.000 claims description 4
- 206010028116 Mucosal inflammation Diseases 0.000 claims description 4
- 201000010927 Mucositis Diseases 0.000 claims description 4
- 206010033645 Pancreatitis Diseases 0.000 claims description 4
- 208000000733 Paroxysmal Hemoglobinuria Diseases 0.000 claims description 4
- 102100036050 Phosphatidylinositol N-acetylglucosaminyltransferase subunit A Human genes 0.000 claims description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
- 206010035664 Pneumonia Diseases 0.000 claims description 4
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 4
- 208000031737 Tissue Adhesions Diseases 0.000 claims description 4
- 239000000443 aerosol Substances 0.000 claims description 4
- 208000026935 allergic disease Diseases 0.000 claims description 4
- 208000005980 beta thalassemia Diseases 0.000 claims description 4
- 230000002490 cerebral effect Effects 0.000 claims description 4
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 4
- 230000012010 growth Effects 0.000 claims description 4
- 230000008595 infiltration Effects 0.000 claims description 4
- 238000001764 infiltration Methods 0.000 claims description 4
- 231100000518 lethal Toxicity 0.000 claims description 4
- 231100001023 lymphopenia Toxicity 0.000 claims description 4
- 230000002071 myeloproliferative effect Effects 0.000 claims description 4
- 201000003045 paroxysmal nocturnal hemoglobinuria Diseases 0.000 claims description 4
- 230000004043 responsiveness Effects 0.000 claims description 4
- 208000007056 sickle cell anemia Diseases 0.000 claims description 4
- 230000037380 skin damage Effects 0.000 claims description 4
- 230000000699 topical effect Effects 0.000 claims description 4
- 230000001052 transient effect Effects 0.000 claims description 4
- 206010003827 Autoimmune hepatitis Diseases 0.000 claims description 3
- 206010055128 Autoimmune neutropenia Diseases 0.000 claims description 3
- 206010050245 Autoimmune thrombocytopenia Diseases 0.000 claims description 3
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 3
- 208000033386 Buerger disease Diseases 0.000 claims description 3
- 206010010099 Combined immunodeficiency Diseases 0.000 claims description 3
- 206010010356 Congenital anomaly Diseases 0.000 claims description 3
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 3
- 102100025621 Cytochrome b-245 heavy chain Human genes 0.000 claims description 3
- 108010092408 Eosinophil Peroxidase Proteins 0.000 claims description 3
- 102100028471 Eosinophil peroxidase Human genes 0.000 claims description 3
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 3
- 206010015124 Ergot poisoning Diseases 0.000 claims description 3
- 201000004939 Fanconi anemia Diseases 0.000 claims description 3
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 3
- 206010020751 Hypersensitivity Diseases 0.000 claims description 3
- 208000014919 IgG4-related retroperitoneal fibrosis Diseases 0.000 claims description 3
- 108010002386 Interleukin-3 Proteins 0.000 claims description 3
- 102000000646 Interleukin-3 Human genes 0.000 claims description 3
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 3
- 206010024229 Leprosy Diseases 0.000 claims description 3
- 201000011062 Li-Fraumeni syndrome Diseases 0.000 claims description 3
- 206010027476 Metastases Diseases 0.000 claims description 3
- 208000002678 Mucopolysaccharidoses Diseases 0.000 claims description 3
- 206010056886 Mucopolysaccharidosis I Diseases 0.000 claims description 3
- 208000034578 Multiple myelomas Diseases 0.000 claims description 3
- 208000008589 Obesity Diseases 0.000 claims description 3
- 208000007117 Oral Ulcer Diseases 0.000 claims description 3
- 206010061924 Pulmonary toxicity Diseases 0.000 claims description 3
- 208000003782 Raynaud disease Diseases 0.000 claims description 3
- 208000012322 Raynaud phenomenon Diseases 0.000 claims description 3
- 206010038979 Retroperitoneal fibrosis Diseases 0.000 claims description 3
- 102100034195 Thrombopoietin Human genes 0.000 claims description 3
- 101710113649 Thyroid peroxidase Proteins 0.000 claims description 3
- 235000018936 Vitellaria paradoxa Nutrition 0.000 claims description 3
- 125000005910 alkyl carbonate group Chemical group 0.000 claims description 3
- 208000006682 alpha 1-Antitrypsin Deficiency Diseases 0.000 claims description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 3
- 230000037182 bone density Effects 0.000 claims description 3
- 238000002659 cell therapy Methods 0.000 claims description 3
- 208000016532 chronic granulomatous disease Diseases 0.000 claims description 3
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims description 3
- 239000004053 dental implant Substances 0.000 claims description 3
- 239000000835 fiber Substances 0.000 claims description 3
- 239000002657 fibrous material Substances 0.000 claims description 3
- 229960000390 fludarabine Drugs 0.000 claims description 3
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 claims description 3
- 239000003517 fume Substances 0.000 claims description 3
- 239000007789 gas Substances 0.000 claims description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 3
- 208000024963 hair loss Diseases 0.000 claims description 3
- 230000003676 hair loss Effects 0.000 claims description 3
- 208000002672 hepatitis B Diseases 0.000 claims description 3
- 208000010710 hepatitis C virus infection Diseases 0.000 claims description 3
- 208000029570 hepatitis D virus infection Diseases 0.000 claims description 3
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 3
- 230000009610 hypersensitivity Effects 0.000 claims description 3
- 201000001881 impotence Diseases 0.000 claims description 3
- 230000009401 metastasis Effects 0.000 claims description 3
- 206010028093 mucopolysaccharidosis Diseases 0.000 claims description 3
- 208000025113 myeloid leukemia Diseases 0.000 claims description 3
- 206010065988 nodular fasciitis Diseases 0.000 claims description 3
- 208000030212 nutrition disease Diseases 0.000 claims description 3
- 235000020824 obesity Nutrition 0.000 claims description 3
- 229960005489 paracetamol Drugs 0.000 claims description 3
- 208000028169 periodontal disease Diseases 0.000 claims description 3
- YIQPUIGJQJDJOS-UHFFFAOYSA-N plerixafor Chemical compound C=1C=C(CN2CCNCCCNCCNCCC2)C=CC=1CN1CCCNCCNCCCNCC1 YIQPUIGJQJDJOS-UHFFFAOYSA-N 0.000 claims description 3
- 231100000374 pneumotoxicity Toxicity 0.000 claims description 3
- 208000003476 primary myelofibrosis Diseases 0.000 claims description 3
- 201000006081 pseudosarcomatous fibromatosis Diseases 0.000 claims description 3
- 210000001147 pulmonary artery Anatomy 0.000 claims description 3
- 201000000306 sarcoidosis Diseases 0.000 claims description 3
- 201000004409 schistosomiasis Diseases 0.000 claims description 3
- 208000002491 severe combined immunodeficiency Diseases 0.000 claims description 3
- 150000003557 thiazoles Chemical class 0.000 claims description 3
- 102100028207 6-phosphogluconate dehydrogenase, decarboxylating Human genes 0.000 claims description 2
- 102100024643 ATP-binding cassette sub-family D member 1 Human genes 0.000 claims description 2
- 201000011452 Adrenoleukodystrophy Diseases 0.000 claims description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 2
- 101710151348 D-3-phosphoglycerate dehydrogenase Proteins 0.000 claims description 2
- 206010014954 Eosinophilic fasciitis Diseases 0.000 claims description 2
- 206010016717 Fistula Diseases 0.000 claims description 2
- 206010061459 Gastrointestinal ulcer Diseases 0.000 claims description 2
- 208000031953 Hereditary hemorrhagic telangiectasia Diseases 0.000 claims description 2
- 208000017604 Hodgkin disease Diseases 0.000 claims description 2
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 2
- 208000015178 Hurler syndrome Diseases 0.000 claims description 2
- 206010067125 Liver injury Diseases 0.000 claims description 2
- 208000035809 Lymphohistiocytosis Diseases 0.000 claims description 2
- 108010049137 Member 1 Subfamily D ATP Binding Cassette Transporter Proteins 0.000 claims description 2
- 201000011442 Metachromatic leukodystrophy Diseases 0.000 claims description 2
- 208000033833 Myelomonocytic Chronic Leukemia Diseases 0.000 claims description 2
- 208000037538 Myelomonocytic Juvenile Leukemia Diseases 0.000 claims description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 2
- 208000009527 Refractory anemia Diseases 0.000 claims description 2
- 206010072684 Refractory cytopenia with unilineage dysplasia Diseases 0.000 claims description 2
- 208000010123 anthracosis Diseases 0.000 claims description 2
- 208000002399 aphthous stomatitis Diseases 0.000 claims description 2
- 210000004204 blood vessel Anatomy 0.000 claims description 2
- 201000010902 chronic myelomonocytic leukemia Diseases 0.000 claims description 2
- 229910003460 diamond Inorganic materials 0.000 claims description 2
- 239000010432 diamond Substances 0.000 claims description 2
- 230000002708 enhancing effect Effects 0.000 claims description 2
- 230000002449 erythroblastic effect Effects 0.000 claims description 2
- 230000003890 fistula Effects 0.000 claims description 2
- 231100000234 hepatic damage Toxicity 0.000 claims description 2
- 239000012678 infectious agent Substances 0.000 claims description 2
- 201000005992 juvenile myelomonocytic leukemia Diseases 0.000 claims description 2
- 230000008818 liver damage Effects 0.000 claims description 2
- 210000003593 megakaryocyte Anatomy 0.000 claims description 2
- 230000000242 pagocytic effect Effects 0.000 claims description 2
- 229940127293 prostanoid Drugs 0.000 claims description 2
- 150000003814 prostanoids Chemical class 0.000 claims description 2
- 208000037999 tubulointerstitial fibrosis Diseases 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 8
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims 2
- 125000001475 halogen functional group Chemical group 0.000 claims 2
- 229960002169 plerixafor Drugs 0.000 claims 2
- 208000030760 Anaemia of chronic disease Diseases 0.000 claims 1
- 229940124186 Dehydrogenase inhibitor Drugs 0.000 claims 1
- 208000004930 Fatty Liver Diseases 0.000 claims 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 claims 1
- 208000022400 anemia due to chronic disease Diseases 0.000 claims 1
- 230000002349 favourable effect Effects 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 125
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 34
- 125000004429 atom Chemical group 0.000 description 20
- 125000004432 carbon atom Chemical group C* 0.000 description 20
- 125000001424 substituent group Chemical group 0.000 description 20
- 230000037396 body weight Effects 0.000 description 19
- 210000004072 lung Anatomy 0.000 description 19
- 210000003491 skin Anatomy 0.000 description 19
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 17
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 17
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 description 17
- 125000005842 heteroatom Chemical group 0.000 description 16
- 229940002612 prodrug Drugs 0.000 description 16
- 239000000651 prodrug Substances 0.000 description 16
- 108060001084 Luciferase Proteins 0.000 description 15
- 239000005089 Luciferase Substances 0.000 description 15
- 125000000524 functional group Chemical group 0.000 description 13
- 230000001684 chronic effect Effects 0.000 description 11
- 235000018102 proteins Nutrition 0.000 description 10
- 230000028327 secretion Effects 0.000 description 10
- 208000000059 Dyspnea Diseases 0.000 description 9
- 206010013975 Dyspnoeas Diseases 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 231100000241 scar Toxicity 0.000 description 9
- 239000012453 solvate Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 208000017667 Chronic Disease Diseases 0.000 description 8
- 239000002552 dosage form Substances 0.000 description 8
- 125000005843 halogen group Chemical group 0.000 description 8
- 210000002216 heart Anatomy 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 208000007107 Stomach Ulcer Diseases 0.000 description 7
- 208000032109 Transient ischaemic attack Diseases 0.000 description 7
- 210000001072 colon Anatomy 0.000 description 7
- 230000003247 decreasing effect Effects 0.000 description 7
- 229940088598 enzyme Drugs 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
- 210000003097 mucus Anatomy 0.000 description 7
- 108020004707 nucleic acids Proteins 0.000 description 7
- 102000039446 nucleic acids Human genes 0.000 description 7
- 230000001737 promoting effect Effects 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 238000006722 reduction reaction Methods 0.000 description 7
- 201000010875 transient cerebral ischemia Diseases 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 208000032544 Cicatrix Diseases 0.000 description 6
- 208000007882 Gastritis Diseases 0.000 description 6
- 208000019693 Lung disease Diseases 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000012190 activator Substances 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 208000009190 disseminated intravascular coagulation Diseases 0.000 description 6
- 235000019441 ethanol Nutrition 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000004927 fusion Effects 0.000 description 6
- 125000001183 hydrocarbyl group Chemical group 0.000 description 6
- 230000000670 limiting effect Effects 0.000 description 6
- 150000007523 nucleic acids Chemical class 0.000 description 6
- 230000036573 scar formation Effects 0.000 description 6
- 230000037387 scars Effects 0.000 description 6
- 208000013220 shortness of breath Diseases 0.000 description 6
- 238000003419 tautomerization reaction Methods 0.000 description 6
- 230000000451 tissue damage Effects 0.000 description 6
- 231100000827 tissue damage Toxicity 0.000 description 6
- 230000000472 traumatic effect Effects 0.000 description 6
- 206010006458 Bronchitis chronic Diseases 0.000 description 5
- 102100021973 Carbonyl reductase [NADPH] 1 Human genes 0.000 description 5
- 206010011224 Cough Diseases 0.000 description 5
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 5
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 206010006451 bronchitis Diseases 0.000 description 5
- 230000015556 catabolic process Effects 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 208000007451 chronic bronchitis Diseases 0.000 description 5
- 208000029742 colonic neoplasm Diseases 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- 230000009545 invasion Effects 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 230000008085 renal dysfunction Effects 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 125000000547 substituted alkyl group Chemical group 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 4
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 101150024938 HPGD gene Proteins 0.000 description 4
- 101000896985 Homo sapiens Carbonyl reductase [NADPH] 1 Proteins 0.000 description 4
- 208000000185 Localized scleroderma Diseases 0.000 description 4
- 206010027982 Morphoea Diseases 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 125000006242 amine protecting group Chemical group 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
- 108091007433 antigens Proteins 0.000 description 4
- 102000036639 antigens Human genes 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 239000000090 biomarker Substances 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 238000011254 conventional chemotherapy Methods 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 230000004064 dysfunction Effects 0.000 description 4
- 210000001671 embryonic stem cell Anatomy 0.000 description 4
- 208000028208 end stage renal disease Diseases 0.000 description 4
- 201000000523 end stage renal failure Diseases 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 230000002008 hemorrhagic effect Effects 0.000 description 4
- 230000004968 inflammatory condition Effects 0.000 description 4
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
- 230000011164 ossification Effects 0.000 description 4
- 210000001778 pluripotent stem cell Anatomy 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 230000037390 scarring Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 208000006386 Bone Resorption Diseases 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- 102000053602 DNA Human genes 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 206010014561 Emphysema Diseases 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 208000001034 Frostbite Diseases 0.000 description 3
- 208000018522 Gastrointestinal disease Diseases 0.000 description 3
- 208000028782 Hereditary disease Diseases 0.000 description 3
- 206010051645 Idiopathic neutropenia Diseases 0.000 description 3
- 208000026350 Inborn Genetic disease Diseases 0.000 description 3
- 206010048858 Ischaemic cardiomyopathy Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 241000125945 Protoparvovirus Species 0.000 description 3
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 3
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 208000027032 Renal vascular disease Diseases 0.000 description 3
- 208000034189 Sclerosis Diseases 0.000 description 3
- 206010043561 Thrombocytopenic purpura Diseases 0.000 description 3
- 125000004442 acylamino group Chemical group 0.000 description 3
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 description 3
- 125000004947 alkyl aryl amino group Chemical group 0.000 description 3
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 3
- 125000004691 alkyl thio carbonyl group Chemical group 0.000 description 3
- 231100000360 alopecia Toxicity 0.000 description 3
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 3
- 210000001367 artery Anatomy 0.000 description 3
- 125000004658 aryl carbonyl amino group Chemical group 0.000 description 3
- 125000005199 aryl carbonyloxy group Chemical group 0.000 description 3
- 125000005200 aryloxy carbonyloxy group Chemical group 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000024279 bone resorption Effects 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 229940109239 creatinine Drugs 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 230000007123 defense Effects 0.000 description 3
- 125000004663 dialkyl amino group Chemical group 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 125000004986 diarylamino group Chemical group 0.000 description 3
- 231100000573 exposure to toxins Toxicity 0.000 description 3
- 230000001605 fetal effect Effects 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 210000004211 gastric acid Anatomy 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 150000004677 hydrates Chemical class 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 230000003211 malignant effect Effects 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 210000004877 mucosa Anatomy 0.000 description 3
- 230000035479 physiological effects, processes and functions Effects 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 208000015670 renal artery disease Diseases 0.000 description 3
- 229920002477 rna polymer Polymers 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 238000011476 stem cell transplantation Methods 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 125000005017 substituted alkenyl group Chemical group 0.000 description 3
- 125000003107 substituted aryl group Chemical group 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 150000003462 sulfoxides Chemical class 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- NNDIXBJHNLFJJP-UHFFFAOYSA-N 20-Hydroxyeicosatetraenoic acid Chemical compound OCCCCCC=CCC=CCC=CCC=CCCCC(O)=O NNDIXBJHNLFJJP-UHFFFAOYSA-N 0.000 description 2
- 108010055851 Acetylglucosaminidase Proteins 0.000 description 2
- 208000009304 Acute Kidney Injury Diseases 0.000 description 2
- 208000003200 Adenoma Diseases 0.000 description 2
- 206010001233 Adenoma benign Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 206010015287 Erythropenia Diseases 0.000 description 2
- 206010018364 Glomerulonephritis Diseases 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 206010019663 Hepatic failure Diseases 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 208000002260 Keloid Diseases 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 208000037062 Polyps Diseases 0.000 description 2
- 102100030122 Protein O-GlcNAcase Human genes 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 208000001647 Renal Insufficiency Diseases 0.000 description 2
- 208000033626 Renal failure acute Diseases 0.000 description 2
- 208000037656 Respiratory Sounds Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 208000005485 Thrombocytosis Diseases 0.000 description 2
- 206010047924 Wheezing Diseases 0.000 description 2
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 201000011040 acute kidney failure Diseases 0.000 description 2
- 125000003158 alcohol group Chemical group 0.000 description 2
- 125000002723 alicyclic group Chemical group 0.000 description 2
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 2
- 230000000735 allogeneic effect Effects 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000031018 biological processes and functions Effects 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 238000010322 bone marrow transplantation Methods 0.000 description 2
- 208000035269 cancer or benign tumor Diseases 0.000 description 2
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000005595 deprotonation Effects 0.000 description 2
- 238000010537 deprotonation reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 210000003979 eosinophil Anatomy 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
- 210000003754 fetus Anatomy 0.000 description 2
- 230000027119 gastric acid secretion Effects 0.000 description 2
- 210000001156 gastric mucosa Anatomy 0.000 description 2
- 208000016361 genetic disease Diseases 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000003803 hair density Effects 0.000 description 2
- 210000003780 hair follicle Anatomy 0.000 description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
- 230000001969 hypertrophic effect Effects 0.000 description 2
- 208000026278 immune system disease Diseases 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 235000015110 jellies Nutrition 0.000 description 2
- 239000008274 jelly Substances 0.000 description 2
- 210000001117 keloid Anatomy 0.000 description 2
- 210000002510 keratinocyte Anatomy 0.000 description 2
- 201000006370 kidney failure Diseases 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 231100000835 liver failure Toxicity 0.000 description 2
- 208000007903 liver failure Diseases 0.000 description 2
- 231100000516 lung damage Toxicity 0.000 description 2
- 206010025135 lupus erythematosus Diseases 0.000 description 2
- 230000001926 lymphatic effect Effects 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 230000000877 morphologic effect Effects 0.000 description 2
- 230000001400 myeloablative effect Effects 0.000 description 2
- 229950006238 nadide Drugs 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 210000001178 neural stem cell Anatomy 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000003169 placental effect Effects 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 230000005588 protonation Effects 0.000 description 2
- 210000000664 rectum Anatomy 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 230000008672 reprogramming Effects 0.000 description 2
- 210000005241 right ventricle Anatomy 0.000 description 2
- 210000004761 scalp Anatomy 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000009168 stem cell therapy Methods 0.000 description 2
- 238000009580 stem-cell therapy Methods 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 2
- 210000004876 tela submucosa Anatomy 0.000 description 2
- 150000003536 tetrazoles Chemical class 0.000 description 2
- 231100001274 therapeutic index Toxicity 0.000 description 2
- 230000008719 thickening Effects 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 210000005166 vasculature Anatomy 0.000 description 2
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- YRTJDWROBKPZNV-UHFFFAOYSA-N 15-Oxoprostaglandin E2 Natural products CCCCCC(=O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O YRTJDWROBKPZNV-UHFFFAOYSA-N 0.000 description 1
- YRTJDWROBKPZNV-KMXMBPPJSA-N 15-dehydro-prostaglandin E2 Chemical compound CCCCCC(=O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O YRTJDWROBKPZNV-KMXMBPPJSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical class O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 1
- LCYAYKSMOVLVRL-UHFFFAOYSA-N 2-butylsulfinyl-4-phenyl-6-thiophen-2-ylthieno[2,3-b]pyridin-3-amine Chemical compound C=12C(N)=C(S(=O)CCCC)SC2=NC(C=2SC=CC=2)=CC=1C1=CC=CC=C1 LCYAYKSMOVLVRL-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PEPBFCOIJRULGJ-UHFFFAOYSA-N 3h-1,2,3-benzodioxazole Chemical compound C1=CC=C2NOOC2=C1 PEPBFCOIJRULGJ-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- CWEAOVXQFWJOSW-UHFFFAOYSA-N 4-phenyl-[1,3]dioxolo[4,5-c]quinoline Chemical compound O1COC2=C1C1=CC=CC=C1N=C2C1=CC=CC=C1 CWEAOVXQFWJOSW-UHFFFAOYSA-N 0.000 description 1
- 102100033051 40S ribosomal protein S19 Human genes 0.000 description 1
- CLRIMWMVEVYXAK-UHFFFAOYSA-N 5-ethylcyclopenta-1,3-diene Chemical compound CCC1C=CC=C1 CLRIMWMVEVYXAK-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 206010000830 Acute leukaemia Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 102100035248 Alpha-(1,3)-fucosyltransferase 4 Human genes 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 208000034048 Asymptomatic disease Diseases 0.000 description 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 108060000903 Beta-catenin Proteins 0.000 description 1
- 102000015735 Beta-catenin Human genes 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 208000033932 Blackfan-Diamond anemia Diseases 0.000 description 1
- 208000019838 Blood disease Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 206010006474 Bronchopulmonary aspergillosis allergic Diseases 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 101710085496 C-X-C motif chemokine 2 Proteins 0.000 description 1
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 1
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 1
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 108090000492 Carbonyl Reductase (NADPH) Proteins 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 206010008469 Chest discomfort Diseases 0.000 description 1
- 206010048832 Colon adenoma Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 208000025212 Constitutional neutropenia Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 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
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 108020005199 Dehydrogenases Proteins 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 206010056340 Diabetic ulcer Diseases 0.000 description 1
- 201000004449 Diamond-Blackfan anemia Diseases 0.000 description 1
- 208000018672 Dilatation Diseases 0.000 description 1
- 206010058314 Dysplasia Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Chemical group 0.000 description 1
- 206010016059 Facial pain Diseases 0.000 description 1
- 206010016228 Fasciitis Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 206010016807 Fluid retention Diseases 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 206010017711 Gangrene Diseases 0.000 description 1
- 206010061172 Gastrointestinal injury Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102100035716 Glycophorin-A Human genes 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 208000000616 Hemoptysis Diseases 0.000 description 1
- 238000012752 Hepatectomy Methods 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001126430 Homo sapiens 15-hydroxyprostaglandin dehydrogenase [NAD(+)] Proteins 0.000 description 1
- 101001022185 Homo sapiens Alpha-(1,3)-fucosyltransferase 4 Proteins 0.000 description 1
- 101001074244 Homo sapiens Glycophorin-A Proteins 0.000 description 1
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 1
- 101000998120 Homo sapiens Interleukin-3 receptor subunit alpha Proteins 0.000 description 1
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 description 1
- 101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 description 1
- 108010038663 Hydroxyprostaglandin Dehydrogenases Proteins 0.000 description 1
- 102000010817 Hydroxyprostaglandin Dehydrogenases Human genes 0.000 description 1
- 241000257303 Hymenoptera Species 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 208000004044 Hypesthesia Diseases 0.000 description 1
- 206010058558 Hypoperfusion 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
- 208000028622 Immune thrombocytopenia Diseases 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- 206010052210 Infantile genetic agranulocytosis Diseases 0.000 description 1
- 102100022338 Integrin alpha-M Human genes 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102100033493 Interleukin-3 receptor subunit alpha Human genes 0.000 description 1
- 206010022653 Intestinal haemorrhages Diseases 0.000 description 1
- 206010022714 Intestinal ulcer Diseases 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- 206010023421 Kidney fibrosis Diseases 0.000 description 1
- 102100020880 Kit ligand Human genes 0.000 description 1
- 101710177504 Kit ligand Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000270322 Lepidosauria Species 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
- 206010024971 Lower respiratory tract infections Diseases 0.000 description 1
- 206010025476 Malabsorption Diseases 0.000 description 1
- 208000004155 Malabsorption Syndromes Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000024556 Mendelian disease Diseases 0.000 description 1
- 206010054949 Metaplasia Diseases 0.000 description 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 125000003047 N-acetyl group Chemical group 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 1
- 208000001388 Opportunistic Infections Diseases 0.000 description 1
- 241000906034 Orthops Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 206010073391 Platelet dysfunction Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 1
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 206010062237 Renal impairment Diseases 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 208000036071 Rhinorrhea Diseases 0.000 description 1
- 206010039101 Rhinorrhoea Diseases 0.000 description 1
- 102000004389 Ribonucleoproteins Human genes 0.000 description 1
- 108010081734 Ribonucleoproteins Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- 101710142587 Short-chain dehydrogenase/reductase Proteins 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 206010040829 Skin discolouration Diseases 0.000 description 1
- 206010072170 Skin wound Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 229920002472 Starch Polymers 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
- 229930006000 Sucrose Natural products 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- 208000002847 Surgical Wound Diseases 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 description 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 1
- 208000002903 Thalassemia Diseases 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 102000036693 Thrombopoietin Human genes 0.000 description 1
- 108010041111 Thrombopoietin Proteins 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 102100038138 WD repeat-containing protein 26 Human genes 0.000 description 1
- 102000013814 Wnt Human genes 0.000 description 1
- 108050003627 Wnt Proteins 0.000 description 1
- 230000004156 Wnt signaling pathway Effects 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 150000001241 acetals Chemical class 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
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002053 acidogenic effect Effects 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 208000037883 airway inflammation Diseases 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000001299 aldehydes Chemical group 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000005089 alkenylaminocarbonyl group Chemical group 0.000 description 1
- 125000005090 alkenylcarbonyl group Chemical group 0.000 description 1
- 125000005157 alkyl carboxy group Chemical group 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 208000006778 allergic bronchopulmonary aspergillosis Diseases 0.000 description 1
- 238000011316 allogeneic transplantation Methods 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000006427 angiogenic response Effects 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 125000005125 aryl alkyl amino carbonyl group Chemical group 0.000 description 1
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical compound O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 208000022806 beta-thalassemia major Diseases 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000009583 bone marrow aspiration Methods 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 210000001217 buttock Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- KWEDUNSJJZVRKR-UHFFFAOYSA-N carbononitridic azide Chemical group [N-]=[N+]=NC#N KWEDUNSJJZVRKR-UHFFFAOYSA-N 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000002612 cardiopulmonary effect Effects 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004534 cecum Anatomy 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000036978 cell physiology Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000024207 chronic leukemia Diseases 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 208000018631 connective tissue disease Diseases 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 125000003493 decenyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000035614 depigmentation Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 208000017574 dry cough Diseases 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 150000002081 enamines Chemical group 0.000 description 1
- 230000008694 endothelial dysfunction Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 125000004494 ethyl ester group Chemical group 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
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 210000003020 exocrine pancreas Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000003352 fibrogenic effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000005519 fluorenylmethyloxycarbonyl group Chemical group 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000002642 gamma-glutamyl group Chemical group 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 230000024924 glomerular filtration Effects 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 210000002175 goblet cell Anatomy 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 229940047650 haemophilus influenzae Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 208000018706 hematopoietic system disease Diseases 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000002390 heteroarenes Chemical class 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000001981 hip bone Anatomy 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 208000034783 hypoesthesia Diseases 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 150000002466 imines Chemical group 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 238000003318 immunodepletion Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 208000033065 inborn errors of immunity Diseases 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000000266 injurious effect Effects 0.000 description 1
- 208000003243 intestinal obstruction Diseases 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 208000016809 linear scleroderma Diseases 0.000 description 1
- 230000006372 lipid accumulation Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000015689 metaplastic ossification Effects 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 238000005065 mining Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 229940074923 mozobil Drugs 0.000 description 1
- 230000000420 mucociliary effect Effects 0.000 description 1
- 210000002894 multi-fate stem cell Anatomy 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 125000004370 n-butenyl group Chemical group [H]\C([H])=C(/[H])C([H])([H])C([H])([H])* 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 210000000885 nephron Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000008976 nose development Effects 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 125000000394 phosphonato group Chemical group [O-]P([O-])(*)=O 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000019612 pigmentation Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 231100000857 poor renal function Toxicity 0.000 description 1
- 235000020004 porter Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 208000028529 primary immunodeficiency disease Diseases 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 238000009613 pulmonary function test Methods 0.000 description 1
- 210000003492 pulmonary vein Anatomy 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 230000001698 pyrogenic effect Effects 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 201000010727 rectal prolapse Diseases 0.000 description 1
- 230000008327 renal blood flow Effects 0.000 description 1
- 210000004994 reproductive system Anatomy 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 210000000614 rib Anatomy 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 230000037370 skin discoloration Effects 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 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
- MWNQXXOSWHCCOZ-UHFFFAOYSA-L sodium;oxido carbonate Chemical compound [Na+].[O-]OC([O-])=O MWNQXXOSWHCCOZ-UHFFFAOYSA-L 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 210000001562 sternum Anatomy 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 125000004426 substituted alkynyl group Chemical group 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 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
- 150000003457 sulfones Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 150000008053 sultones Chemical class 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 125000005063 tetradecenyl group Chemical group C(=CCCCCCCCCCCCC)* 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 201000003067 thrombocytopenia due to platelet alloimmunization Diseases 0.000 description 1
- 230000008467 tissue growth Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 210000003384 transverse colon Anatomy 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
- 230000037314 wound repair Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- 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
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/193—Colony stimulating factors [CSF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
-
- 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
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
-
- 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
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- 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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/04—Preparations for care of the skin for chemically tanning the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q7/00—Preparations for affecting hair growth
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Urology & Nephrology (AREA)
- Zoology (AREA)
- Developmental Biology & Embryology (AREA)
- Cell Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Reproductive Health (AREA)
- Toxicology (AREA)
- Endocrinology (AREA)
- Psychology (AREA)
- Gynecology & Obstetrics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
Abstract
Description
本出願は、2015年4月14日に出願された米国仮特許出願第62/147,305号(その対象物はその全体が参照により本明細書に組み込まれる)について優先権を主張する。
この発明は国立衛生研究所により授与された認可番号R01CA127306、R01CA127306−03S1、1P01CA95471−10、AND5P50CA150964の下、政府支援によりなされた。米国政府は本発明に対し一定の権利を有し得る。
X6はNまたはCRcであり;
R1は、−(CH2)n1CH3(n1=0−7)、
CFyHz(y+z=3)、CClyHz(y+z=3)、OH、OAc、OMe、R71、OR72、CN、N(R73)2、
R5は、H、OH、Cl、F、NH2、N(R76)2、およびOR77からなる群より選択され;
R6およびR7はそれぞれ独立して、下記の1つとすることができ:
R6がH、非置換チオフェン、または非置換チアゾールであり、およびR1がブチルである場合、R7は、水素ではなく;およびR6がH、または非置換フェニル、チオフェン、またはチアゾールであり、およびR1がベンジルまたは(CH2)n5(CH3)(n5=0−5)である場合、R7は非置換フェニルではない。
X6はNまたはCRcであり;
X7はNまたはCであり;
R1は、−(CH2)n1CH3(n1=0−7)、
CFyHz(y+z=3)、CClyHz(y+z=3)、OH、OAc、OMe、R71、OR72、CN、N(R73)2、
R5は、H、OH、Cl、F、NH2、N(R76)2、およびOR77からなる群より選択され;
R7はそれぞれ独立して、下記の1つとすることができ:
R1がブチルである場合、R7は水素でなく;およびR1が(CH2)n5(CH3)(n5=0−5)である場合、R7は非置換フェニルではない。
X6はNまたはCRcであり;
X7はNまたはCであり;
R1は、−(CH2)n1CH3(n1=0−7)、
CFyHz(y+z=3)、CClyHz(y+z=3)、OH、OAc、OMe、R71、OR72、CN、N(R73)2、
R5は、H、OH、Cl、F、NH2、N(R76)2、およびOR77からなる群より選択され;
R7は各々独立して、下記の1つを含む5員複素環とすることができ:
R7は
X6はNまたはCRcであり;
R1は、−(CH2)n1CH3(n1=0−7)、
CFyHz(y+z=3)、CClyHz(y+z=3)、OH、OAc、OMe、R71、OR72、CN、N(R73)2、
R5は、H、OH、Cl、F、NH2、N(R76)2、およびOR77からなる群より選択され;
R6およびR7はそれぞれ独立して、下記の1つとすることができ:
R6がH、非置換チオフェン、または非置換チアゾールであり、およびR1がブチルである場合、R7は、水素ではなく;およびR6がH、または非置換フェニル、チオフェン、またはチアゾールであり、およびR1がベンジルまたは(CH2)n5(CH3)(n5=0−5)である場合、R7は非置換フェニルではない。
X6はNまたはCRcであり;
X7はNまたはCであり;
R1は、−(CH2)n1CH3(n1=0−7)、
CFyHz(y+z=3)、CClyHz(y+z=3)、OH、OAc、OMe、R71、OR72、CN、N(R73)2、
R5は、H、OH、Cl、F、NH2、N(R76)2、およびOR77からなる群より選択され;
R7はそれぞれ独立して、下記の1つとすることができ:
R1がブチルである場合、R7は水素でなく;およびR1が(CH2)n5(CH3)(n5=0−5)である場合、R7は非置換フェニルではない。
X6はNまたはCRcであり;
X7はNまたはCであり;
R1は、−(CH2)n1CH3(n1=0−7)、
CFyHz(y+z=3)、CClyHz(y+z=3)、OH、OAc、OMe、R71、OR72、CN、N(R73)2、
を含む分枝または直鎖アルキルからなる群より選択され;
R5は、H、OH、Cl、F、NH2、N(R76)2、およびOR77からなる群より選択され;
R7はそれぞれ独立して、下記の1つとすることができ:
ここで、R7は下記ではない:
リード化合物SW033291、15−PGDH阻害剤の類似体の分析
この実施例は、SW033291の一群の構造類似体についてのデータを提供する。提供されるデータはインビトロアッセイにおいて組換え15−PGDHの酵素活性を阻害するための各化合物のIC50である。組換え15−PGDHは、他に特に規定がなければヒトである。加えて、実施例は、pH7またはpH4クエン酸塩緩衝溶液中での選択された類似体についての水溶解度データを提供する。
SW212835の合成:
SW213150の合成:
SW213156の合成:
1 Lorente, A.; Navio, J. L. Garcia; Vaquero, J. J.; Soto, J. L. J. Heterocycl. Chem., 1985 , 22, 49.
2 Hoyt, A. L.; Blakemore, P. R. Tetrahedron Lett. 2015, 56. 2980.
3 Girgis, A. S.; Mishriky, N.; Farag, A. M.; El−Eraky, W. I.; Farag, H. Eur. J. Med. Chem. 2008, 43, 1818 .
4 特許: BOEHRINGER INGELHEIM PHARMACEUTICALS, INC.: WO2005/90333 A1号, 2005.
5 Seto, M.; Miyamoto, N.; Aikawa, K.; Aramaki, Y.; Kanzaki, N.; Iizawa, Y.; Baba, M.; Shiraishi, M. Bioorg. Med. Chem., 2005 , 13, 363
6 Zhou, Y.; Gong, Y. Eur. J. Org. Chem. 2011, 30, 6092
Claims (99)
- 式(I)を有する化合物、ならびにその薬学的に許容される塩:
X6はNまたはCRcであり;
R1は、−(CH2)n1CH3(n1=0−7)、
CFyHz(y+z=3)、CClyHz(y+z=3)、OH、OAc、OMe、R71、OR72、CN、N(R73)2、
を含む分枝または直鎖アルキルからなる群より選択され;
R5は、H、OH、Cl、F、NH2、N(R76)2、およびOR77からなる群より選択され;
R6およびR7はそれぞれ独立して、下記の1つとすることができ:
R6がH、非置換チオフェン、または非置換チアゾールであり、およびR1がブチルである場合、R7は、水素ではなく;およびR6がH、または非置換フェニル、チオフェン、またはチアゾールであり、およびR1がベンジルまたは(CH2)n5(CH3)(n5=0−5)である場合、R7は非置換フェニルではない。 - X6はNまたはCHである、請求項1に記載の化合物。
- R6は、5−6個の環原子を含む、置換もしくは非置換ヘテロシクリルである、請求項1〜2のいずれかに記載の化合物。
- R6は置換もしくは非置換チオフェン、チアゾール、オキサゾール、イミダゾール、ピリジン、またはフェニルである、請求項1〜3のいずれかに記載の化合物。
- nが1である、請求項1〜4のいずれかに記載の化合物。
- R7は、H、置換もしくは非置換アリール、置換もしくは非置換シクロアルキル、および置換もしくは非置換ヘテロシクリル、アルキル、またはカルボキシ、例えばカルボン酸(−CO2H)、カルボキシエステル(−CO2アルキル)およびカルボキサミド[−CON(H)(アルキル)または−CO2N(アルキル)2]からなる群より選択される、請求項1〜5のいずれかに記載の化合物。
- 式(III)を有する化合物、ならびにその薬学的に許容される塩:
X6はNまたはCRcであり;
X7はNまたはCであり;
R1は、−(CH2)n1CH3(n1=0−7)、
CFyHz(y+z=3)、CClyHz(y+z=3)、OH、OAc、OMe、R71、OR72、CN、N(R73)2、
を含む分枝または直鎖アルキルからなる群より選択され;
R5は、H、OH、Cl、F、NH2、N(R76)2、およびOR77からなる群より選択され;
R7はそれぞれ独立して、下記の1つとすることができ:
R7は、下記ではない:
- X6はNまたはCHである、請求項8に記載の化合物。
- nは1である、請求項8〜9のいずれかに記載の化合物。
- 医薬組成物の調製における、請求項1〜12のいずれかに記載の化合物の使用。
- 短鎖デヒドロゲナーゼ酵素の活性を阻害するための、短鎖デヒドロゲナーゼ阻害剤としての、請求項1〜12のいずれかに記載の化合物の使用。
- 15−PGDH酵素の活性を阻害するための15−PGDH阻害剤としての、請求項1〜12のいずれかに記載の化合物の使用。
- 前記阻害剤は、約5nM〜約10nMの組換え15−PGDH濃度にて、1μM未満のIC50で、好ましくは250nM未満のIC50で、より好ましくは50nM未満のIC50で、より好ましくは10nM未満のIC50で、より好ましくは5nM未満のIC50で、組換え15−PGDHの酵素活性を阻害する、請求項14または15のいずれかに記載の使用。
- 前記阻害剤は被験体の組織に、前記組織中のプロスタグランジンレベルを増加させるのに有効な量で投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、局所組成物中で提供される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、被験体の皮膚に、皮膚の色素沈着および/または発毛を促進および/または刺激する、および/または脱毛を阻害する、および/または皮膚ダメージまたは炎症を治療するために適用される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、創傷治癒、組織修復、および/または組織再生を促進するために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、口腔潰瘍、歯周病、大腸炎、潰瘍性大腸炎、胃腸潰瘍、炎症性腸疾患、血行障害、レイノー病、バージャー病、糖尿病性ニューロパチー、肺動脈高血圧、心血管疾患、および腎疾患の少なくとも1つを治療するために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、被験体に、プロスタグランジン応答病状におけるアゴニストの治療効果を増強する目的で、プロスタノイドアゴニストと組み合わせて投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、前記被験体の組織に、組織幹細胞を増加させるために投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、組織移植片ドナー、骨髄移植片ドナー、および/または造血幹細胞ドナーに、ドナー組織移植片、ドナー骨髄移植片、および/またはドナー造血幹細胞移植片の適応度を増加させるために投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、被験体の骨髄に、前記被験体内の幹細胞を増加させるために投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、被験体の骨髄に、ドナー移植片としての前記骨髄の適応度を増加させるために投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、被験体の造血幹細胞の調製物に、ドナー移植片としての前記幹細胞調製物の適応度を増加させるために投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、被験体の末梢血造血幹細胞の調製物に、ドナー移植片としての幹細胞調製物の適応度を増加させるために投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、臍帯血幹細胞の調製物に、ドナー移植片としての前記幹細胞調製物の適応度を増加させるために投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、臍帯血幹細胞の調製物に、移植に必要とされる臍帯血の単位数を減少させるために投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、組織移植片拒絶を緩和するために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、組織および/または骨髄移植片生着を増強させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、前記被験体または前記被験体の骨髄の放射線療法、化学療法、または免疫抑制療法による治療後、骨髄移植片生着を増強させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、前駆幹細胞移植片、造血幹細胞移植片、または臍帯血幹細胞移植片の生着を増強させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、前記被験体または前記被験体の骨髄の放射線療法、化学療法、または免疫抑制療法による治療後、造血幹細胞移植片、または臍帯幹細胞移植片の生着を増強させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、前記被験体中への移植に必要とされる臍帯血の単位数を減少させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、組織移植片移植、骨髄移植、および/または造血幹細胞移植、または臍帯幹細胞移植のレシピエントに、他の治療または成長因子の投与を減少させるために投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、被験体または被験体の組織移植片に、移植片拒絶を緩和するために投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、被験体または被験体の組織移植片に、移植片生着を増強させるために投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、被験体または被験体の組織移植片に、前記被験体または前記被験体の骨髄の放射線療法、化学療法、または免疫抑制療法による治療後の移植片生着を増強させるために投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、被験体または被験体の骨髄に、放射線への曝露の毒性または致死的効果に対する抵抗性を付与するために投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、被験体または被験体の骨髄に、シトキサンの毒性効果、フルダラビンの毒性効果、化学療法の毒性効果、または免疫抑制療法の毒性効果に対する抵抗性を付与するために投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、被験体または被験体の骨髄に、感染を減少させるために投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、骨髄、造血幹細胞、または臍帯血による造血細胞移植後の好中球数を増加させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、好中球減少症(neutropia)を有する被験体において、化学療法投与または放射線療法後の好中球数を増加させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、再生不良性貧血、脊髄形成異常症、骨髄線維症、他の骨髄疾患による好中球減少症、薬物性好中球減少症、自己免疫性好中球減少症、特発性好中球減少症、またはウイルス感染後の好中球減少症を有する被験体において好中球数を増加させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、好中球減少症(neutropia)を有する被験体において好中球数を増加させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、骨髄、造血幹細胞、または臍帯血による造血細胞移植後の血小板数を増加させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、化学療法投与または放射線療法後の、血小板減少症を有する被験体において血小板数を増加させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、再生不良性貧血、脊髄形成異常症、骨髄線維症、他の骨髄疾患による血小板減少症、薬物性血小板減少症、自己免疫性血小板減少症、特発性血小板減少性紫斑病、特発性血小板減少症、またはウイルス感染後の血小板減少症を有する被験体において血小板数を増加させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、血小板減少症を有する被験体において血小板数を増加させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、骨髄、造血幹細胞、または臍帯血による造血細胞移植後の、赤血球数、またはヘマトクリット、またはヘモグロビンレベルを増加させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、化学療法投与または放射線療法後の、貧血を有する被験体において赤血球数、またはヘマトクリット、またはヘモグロビンレベルを増加させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、再生不良性貧血、脊髄形成異常症、骨髄線維症、骨髄の他の障害による貧血、薬物性貧血、免疫介在性貧血、慢性疾患の貧血、ウイルス感染後の貧血、または原因不明の貧血を有する被験体において、赤血球数、またはヘマトクリット、またはヘモグロビンレベルカウントを増加させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、貧血を有する被験体において赤血球数、またはヘマトクリット、またはヘモグロビンレベルを増加させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、骨髄、造血幹細胞、または臍帯血による造血細胞移植後の骨髄幹細胞を増加させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、化学療法投与または放射線療法後の被験体において骨髄幹細胞を増加させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、再生不良性貧血、脊髄形成異常症、骨髄線維症、骨髄の他の障害、薬物性血球減少症、免疫血球減少症、ウイルス感染後の血球減少症、または血球減少症を有する被験体において骨髄幹細胞を増加させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、血球減少症の存在下、サイトカインへの応答性を増加させるために、被験体に投与され、血球減少症は、下記のいずれかを含み:好中球減少症、血小板減少症、リンパ球減少症および貧血;ならびにサイトカインは、下記のいずれかを含む15−PGDH阻害剤により増強される増加した応答性を有する、請求項13〜16のいずれかに記載の使用:G−CSF、GM−CSF、EPO、IL−3、IL−6、TPO、TPO−RA(トロンボポエチン受容体アゴニスト)、およびSCF。
- 前記阻害剤は、放射線由来の肺毒性を減少させるために、被験体または被験体の骨髄に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、骨密度を増加させる、骨粗鬆症を治療する、骨折の治癒を促進する、または骨手術または関節置換後の治癒を促進するために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、骨インプラント、人工インプラント、歯科インプラントおよび移植骨に対する骨の治癒を促進するために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、被験体または被験体の腸に、前記腸中の幹細胞を増加させるために投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、被験体または被験体の腸に、前記腸中の幹細胞を増加させる、および放射線への曝露の毒性または致死的効果または化学療法による治療に起因する毒性、致死的、または粘膜炎効果に対する抵抗性を付与するために投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、被験体または被験体の腸に、放射線への曝露の毒性または致死的効果または化学療法による治療に起因する毒性、致死的、または粘膜炎効果に対する抵抗性を付与するために投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、被験体または被験体の腸に、大腸炎、潰瘍性大腸炎、または炎症性腸疾患のための治療として投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、肝臓手術後、生体肝提供後、肝移植後、または毒素による肝損傷後の肝再生を増加させるために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、アセトアミノフェンおよび関連化合物を含む肝臓毒素からの回復またはこれに対する抵抗性を促進するために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、勃起不全を治療するために、被験体に投与される、請求項13〜16のいずれかに記載の使用。
- 前記阻害剤は、15−PGDHを発現する癌の成長、増殖、または転移の少なくとも1つを阻害するために投与される、請求項13〜16のいずれかに記載の使用。
- 細胞治療の必要な被験体を治療する方法であって、前記被験体に治療的有効量の、請求項1−12に記載の15−PGDH阻害剤が投与されたヒト造血幹細胞を含む調製物および/またはヒト造血幹細胞および請求項1−12に記載の15−PGDH阻害剤を含む治療組成物を投与することを含む方法。
- ヒト造血幹細胞を受けた、および/または前記調製物および/または前記治療組成物を受けた被験体に、請求項1−12に記載の15−PGDH阻害剤を投与することをさらに含む、請求項128に記載の方法。
- 前記被験体は、急性骨髄性白血病(AML)、急性リンパ性白血病(ALL)、慢性骨髄性白血病(CML)、慢性リンパ性白血病(CLL)、若年性骨髄単球性白血病、ホジキンリンパ腫、非ホジキンリンパ腫、多発性骨髄腫、重症再生不良性貧血、ファンコニ貧血、発作性夜間ヘモグロビン尿症(PNH)、赤芽球癆、無巨核球性/先天性血小板減少症、重症複合免疫不全症候群(SCID)、ウィスコット・アルドリッチ症候群、重症型βサラセミア、鎌状赤血球症、ハーラー症候群、副腎白質ジストロフィー、異染性白質ジストロフィー、脊髄形成異常症、不応性貧血、慢性骨髄単球性白血病、原発性骨髄線維症、家族性赤血球貪食性リンパ組織球増多症、固形腫瘍、慢性肉芽腫性疾患、ムコ多糖症、またはダイアモンド・ブラックファン貧血を有する、請求項71に記載の方法。
- 虚血組織または虚血により損傷された組織と関連する少なくとも1つの症状を有する被験体を治療する方法であって、前記被験体に治療的有効量の、請求項1−12に記載の15−PGDH阻害剤が投与されたヒト造血幹細胞を含む調製物および/またはヒト造血幹細胞および請求項1−12に記載の15−PGDH阻害剤を含む治療組成物を投与することを含む、方法。
- 前記虚血は、下記の少なくとも1つと関連する、請求項74に記載の方法:急性冠症候群、急性肺損傷(ALI)、急性心筋梗塞(AMI)、急性呼吸促迫症候群(ARDS)、動脈閉塞症、動脈硬化症、関節軟骨欠損、無菌性全身性炎症、アテローム動脈硬化性心血管疾患、自己免疫疾患、骨折、骨折、脳浮腫、脳低灌流、バージャー病、熱傷、癌、心血管疾患、軟骨損傷、脳梗塞、脳虚血、脳卒中、脳血管疾患、化学療法誘発性ニューロパチー、慢性感染、慢性腸間膜虚血、跛行、うっ血性心不全、結合組織損傷、挫傷、冠動脈疾患(CAD)、重症虚血肢(CLI)、クローン病、深部静脈血栓症、深創傷、遅延性潰瘍治癒、遅延性創傷治癒、糖尿病(I型およびII型)、糖尿病性ニューロパチー、糖尿病誘発性虚血、播種性血管内凝固(DIC)、塞栓性脳虚血、移植片対宿主病、遺伝性出血性毛細血管拡張性虚血性血管疾患、過酸素症損傷、低酸素症、炎症、炎症性腸疾患、炎症疾患、損傷腱、間欠性跛行、腸管虚血、虚血、虚血性脳疾患、虚血性心疾患、虚血性末梢血管疾患、虚血性胎盤、虚血性腎疾患、虚血性血管疾患、虚血性−再灌流傷害、裂傷、左冠動脈主幹部病変、虚血肢、下肢虚血、心筋梗塞、心筋虚血、臓器虚血、変形性関節症、骨粗鬆症、骨肉腫、パーキンソン病、末梢動脈疾患(PAD)、末梢動脈疾患、末梢性虚血、末梢性ニューロパチー、末梢血管疾患、前癌、肺浮腫、肺塞栓症、リモデリング障害、腎虚血、網膜虚血、網膜症、敗血症、皮膚潰瘍、固形臓器移植、脊髄損傷、脳卒中、肋軟骨下骨嚢胞、血栓症、血栓性脳虚血、組織虚血、一過性脳虚血発作(TIA)、外傷性脳損傷、潰瘍性大腸炎、腎臓の血管疾患、血管炎症状態、フォンヒッペル・リンダウ症候群、および組織または臓器に対する創傷。
- 被験体に請求項1−12に記載の15−PGDH阻害剤投与することを含む、その必要のある被験体において好中球を増加させる方法。
- 造血サイトカインを、15−PGDH阻害剤と組み合わせて投与することをさらに含む、請求項76に記載の方法。
- 被験体に請求項1−12に記載の15−PGDH阻害剤を投与することを含む、その必要のある被験体において、末梢血造血幹細胞の数を増加させる、および/またはこれを動員する方法。
- G−CSFを、15−PGDH阻害剤と組み合わせて投与することをさらに含む、請求項78に記載の方法。
- 造血サイトカインを、15−PGDH阻害剤と組み合わせて投与することをさらに含む、請求項78に記載の方法。
- プレリキサホルを、15−PGDH阻害剤と組み合わせて投与することをさらに含む、請求項78に記載の方法。
- 末梢血造血幹細胞の数を増加させる、および/またはこれを動員することが、造血幹細胞移植において使用される、請求項78〜81のいずれかに記載の方法。
- 被験体の血液または骨髄に、請求項1−12に記載の15−PGDH阻害剤を投与することを含む、血液または骨髄中の造血幹細胞の数を増加させる方法。
- G−CSFを、15−PGDH阻害剤と組み合わせて投与することをさらに含む、請求項83に記載の方法。
- 造血サイトカインを、15−PGDH阻害剤と組み合わせて投与することをさらに含む、請求項83に記載の方法。
- プレリキサホルを、15−PGDH阻害剤と組み合わせて投与することをさらに含む、請求項83に記載の方法。
- 被験体に治療的有効量の請求項1−12に記載の15−PGDH阻害剤を投与することを含む、その必要のある被験体において疾患、障害または病状を治療または防止する方法。
- 前記線維性疾患、障害または病状は、全部もしくは一部において、線維性材料の過剰生成、例えば、細胞外マトリクス内での線維化材料の過剰生成、または正常な組織要素のマトリクス関連成分の異常な、非機能性の、および/または過剰な蓄積による置き換えにより特徴付けられる、請求項87に記載の方法。
- 前記線維性疾患、障害または病状は、全身性硬化症、多巣性線維硬化症、腎性全身性線維症、強皮症、強皮症移植片対宿主病、腎線維症、糸球体硬化症、腎尿細管間質性線維症、進行性腎疾患または糖尿病性腎症、心臓線維症、肺線維症(pulomanry fibrosis)、糸球体硬化肺線維症、特発性肺線維症、珪肺症、石綿肺、間質性肺疾患、間質性線維化肺疾患、化学療法/放射線誘発肺線維症、口腔線維症、心内膜心筋線維症、三角筋線維症、膵炎、炎症性腸疾患、クローン病、結節性筋膜炎(nodular fascilitis)、好酸球性筋膜炎、正常筋組織の様々な程度における線維組織による置き換えにより特徴付けられる全般線維症症候群、後腹膜線維症、肝線維症、肝硬変、慢性腎不全;骨髄線維症、骨髄−線維症、薬物性麦角中毒、リ・フラウメニ症候群における神経膠芽腫、孤発性神経膠芽腫、骨髄性(myleoid)白血病、急性骨髄性白血病、骨髄異形成症候群、骨髄増殖性症候群(myeloproferative syndrome)、婦人科系癌、カポジ肉腫、ハンセン病、コラーゲン大腸炎、急性線維症、および臓器特異的線維症からなる群より選択される、請求項87に記載の方法。
- 前記線維性疾患、障害または病状は肺の線維症を含む、請求項87に記載の方法。
- 前記肺の線維症は、肺線維症、肺高血圧、慢性閉塞性肺疾患(COPD)、喘息、特発性肺線維症、サルコイドーシス、嚢胞性線維症、家族性肺線維症、珪肺症、石綿肺、炭坑夫塵肺、炭素塵肺症、過敏性肺炎、無機ダストの吸入により引き起こされる肺線維症、感染病原体により引き起こされる肺線維症、有害ガス、エアロゾル、化学ダスト、ヒュームまたは蒸気の吸入により引き起こされる肺線維症、薬物性間質性肺疾患、または肺高血圧、およびそれらの組み合わせからなる群より選択される、請求項90に記載の方法。
- 前記肺の線維症は嚢胞性線維症である、請求項91に記載の方法。
- 前記線維性疾患、障害または病状は腎線維症を含む、請求項87に記載の方法。
- 前記線維性疾患、障害または病状は肝線維症を含む、請求項87に記載の方法。
- 前記肝線維症は、慢性肝疾患、ウイルス誘発性肝硬変、B型肝炎ウイルス感染、C型肝炎ウイルス感染、D型肝炎ウイルス感染、住血吸虫症、原発性胆汁性肝硬変、アルコール性肝疾患または非アルコール性脂肪性肝炎(NASH)、NASH関連肝硬変肥満、糖尿病、タンパク質栄養障害、冠動脈疾患、自己免疫性肝炎、嚢胞性線維症、α1アンチトリプシン欠損症、原発性胆汁性肝硬変、薬物反応および毒素への曝露、またはそれらの組み合わせに起因する、請求項95に記載の方法。
- 前記線維性疾患、障害または病状は心臓の線維症を含む、請求項87に記載の方法。
- 前記線維性疾患、障害または病状は全身性硬化症である、請求項87に記載の方法。
- 前記線維性疾患、障害または病状は手術後癒着形成により引き起こされる、請求項87に記載の方法。
- 前記15−PGDH阻害剤は、前記治療される被験体の組織または臓器において、コラーゲン沈着、炎症性サイトカイン発現、および/または炎症細胞浸潤を低減または阻害するのに有効な量で投与される、請求項87に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201562147305P | 2015-04-14 | 2015-04-14 | |
US62/147,305 | 2015-04-14 | ||
PCT/US2016/027549 WO2016168472A1 (en) | 2015-04-14 | 2016-04-14 | Compositions and methods of modulating short-chain dehydrogenase activity |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2018511616A true JP2018511616A (ja) | 2018-04-26 |
JP2018511616A5 JP2018511616A5 (ja) | 2019-05-30 |
Family
ID=57127188
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017553122A Pending JP2018511616A (ja) | 2015-04-14 | 2016-04-14 | 短鎖デヒドロゲナーゼ活性を調節する組成物および方法 |
Country Status (8)
Country | Link |
---|---|
US (3) | US20180118756A1 (ja) |
EP (1) | EP3283074A4 (ja) |
JP (1) | JP2018511616A (ja) |
CN (1) | CN108012528A (ja) |
AU (1) | AU2016248080A1 (ja) |
CA (1) | CA2982784A1 (ja) |
HK (1) | HK1250651A1 (ja) |
WO (1) | WO2016168472A1 (ja) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11690847B2 (en) | 2016-11-30 | 2023-07-04 | Case Western Reserve University | Combinations of 15-PGDH inhibitors with corticosteroids and/or TNF inhibitors and uses thereof |
US11718589B2 (en) | 2017-02-06 | 2023-08-08 | Case Western Reserve University | Compositions and methods of modulating short-chain dehydrogenase |
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2870666A1 (en) | 2012-04-16 | 2013-10-24 | Case Western Reserve University | Compositions and methods of modulating 15-pgdh activity |
US9801863B2 (en) | 2012-04-16 | 2017-10-31 | Case Western Reserve University | Inhibitors of short-chain dehydrogenase activity for modulating hematopoietic stem cells and hematopoiesis |
AU2014342811B2 (en) | 2013-10-15 | 2019-01-03 | Board Of Regents Of The University Of Texas System | Compositions and methods of modulating short-chain dehydrogenase activity |
EP3267995A4 (en) | 2015-03-08 | 2019-02-27 | Case Western Reserve University | INHIBITORS OF SHORT CHAIN DEHYDROGENASE ACTIVITY FOR THE TREATMENT OF FIBROSIS |
WO2018017582A1 (en) * | 2016-07-18 | 2018-01-25 | Case Western Reserve University | Inhibitors of short-chain dehydrogenase activity for promoting neurogenesis and inhibiting nerve cell death |
WO2018187810A1 (en) * | 2017-04-07 | 2018-10-11 | Case Western Reserve University | Inhibitors of short-chain dehydrogenase activity for treating coronary disorders |
EP3781154A4 (en) * | 2018-04-04 | 2022-02-23 | Case Western Reserve University | COMPOSITIONS AND METHODS FOR TREATING KIDNEY DAMAGE |
JOP20210115A1 (ar) | 2018-11-21 | 2023-01-30 | Univ Texas | تركيبات وطرق لتعديل نشاط ديهيدروجيناز بسلسلة قصيرة |
CN114206337A (zh) * | 2019-06-11 | 2022-03-18 | 莱兰斯坦福初级大学评议会 | 通过抑制15-羟基前列腺素脱氢酶(15-pgdh)使老化组织复壮的方法 |
KR20230011910A (ko) * | 2020-02-21 | 2023-01-25 | 케이스 웨스턴 리저브 유니버시티 | 신장 손상을 치료하기 위한 조성물 및 방법 |
TW202208376A (zh) | 2020-05-20 | 2022-03-01 | 美國凱斯西方瑞瑟夫大學 | 調節短鏈脫氫酶活性之組成物及方法 |
EP4232026A1 (en) * | 2020-10-23 | 2023-08-30 | The Board of Trustees of the Leland Stanford Junior University | Elevation of mitochondrial biogenesis and function by inhibition of prostaglandin degrading enzyme 15-pgdh |
EP4259154A1 (en) * | 2020-12-09 | 2023-10-18 | The Board of Trustees of the Leland Stanford Junior University | Inhibition of prostaglandin degrading enzyme 15-pgdh to improve joint structure and function |
WO2023143432A1 (zh) * | 2022-01-28 | 2023-08-03 | 赛诺哈勃药业(成都)有限公司 | 一种调控15-pgdh活性的化合物及其制备方法 |
TW202346303A (zh) * | 2022-04-13 | 2023-12-01 | 大陸商賽諾哈勃藥業(成都)有限公司 | 一種調控15-pgdh活性的化合物、包含其的藥物組合物及其用途 |
WO2024099429A1 (zh) * | 2022-11-11 | 2024-05-16 | 赛诺哈勃药业(成都)有限公司 | 一种调控15-pgdh活性的化合物及其制备方法 |
WO2024104317A1 (zh) * | 2022-11-14 | 2024-05-23 | 武汉人福创新药物研发中心有限公司 | 抑制15-pgdh的化合物及其用途 |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6281227B1 (en) * | 1996-12-13 | 2001-08-28 | Aventis Pharma Deutschland Gmbh | Sulfonic acid sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds |
JP2004528319A (ja) * | 2001-03-30 | 2004-09-16 | ファイザー・プロダクツ・インク | ピリダジノンアルドースレダクダーゼ阻害物質 |
JP2009535335A (ja) * | 2006-04-26 | 2009-10-01 | ジェネンテック・インコーポレーテッド | ホスホイノシチド3−キナーゼ抑制剤化合物およびその使用方法 |
WO2010045017A1 (en) * | 2008-10-13 | 2010-04-22 | Janssen Pharmaceutica Nv | Amines and sulfoxides of thieno [2,3-d] pyrimidine and their use as adenosine a2a receptor antagonists |
WO2013158649A1 (en) * | 2012-04-16 | 2013-10-24 | Case Western Reserve University | Compositions and methods of modulating 15-pgdh activity |
JP2018511581A (ja) * | 2015-03-08 | 2018-04-26 | ケース ウエスタン リザーブ ユニバーシティ | 線維症を処置するための短鎖デヒドロゲナーゼ活性阻害剤 |
JP6517197B2 (ja) * | 2013-10-15 | 2019-05-22 | ケース ウエスタン リザーブ ユニバーシティ | 短鎖デヒドロゲナーゼ活性を調節する組成物および方法 |
JP2019078488A (ja) * | 2017-10-25 | 2019-05-23 | ダイキン工業株式会社 | 空気調和装置 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4904672A (en) * | 1987-01-30 | 1990-02-27 | Merck & Co., Inc. | Derivatives of 3-hydroxyazabenzo[b]thiophene useful as 5-lipoxygenase inhibitors |
JP4667867B2 (ja) * | 2002-08-02 | 2011-04-13 | メルク・シャープ・エンド・ドーム・コーポレイション | 置換フロ[2,3−b]ピリジン誘導体 |
US7645881B2 (en) * | 2004-07-22 | 2010-01-12 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
WO2010077101A2 (ko) * | 2008-12-30 | 2010-07-08 | 조선대학교산학협력단 | 신규한 티아졸리딘디온 유도체 및 그의 용도 |
US9801863B2 (en) * | 2012-04-16 | 2017-10-31 | Case Western Reserve University | Inhibitors of short-chain dehydrogenase activity for modulating hematopoietic stem cells and hematopoiesis |
-
2016
- 2016-04-14 CA CA2982784A patent/CA2982784A1/en not_active Abandoned
- 2016-04-14 AU AU2016248080A patent/AU2016248080A1/en not_active Abandoned
- 2016-04-14 US US15/566,637 patent/US20180118756A1/en not_active Abandoned
- 2016-04-14 WO PCT/US2016/027549 patent/WO2016168472A1/en unknown
- 2016-04-14 JP JP2017553122A patent/JP2018511616A/ja active Pending
- 2016-04-14 EP EP16780752.8A patent/EP3283074A4/en not_active Withdrawn
- 2016-04-14 CN CN201680034932.5A patent/CN108012528A/zh active Pending
-
2018
- 2018-08-08 HK HK18110182.7A patent/HK1250651A1/zh unknown
-
2020
- 2020-05-08 US US16/869,879 patent/US20210094968A1/en not_active Abandoned
-
2023
- 2023-10-05 US US18/481,787 patent/US20240174688A1/en active Pending
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6281227B1 (en) * | 1996-12-13 | 2001-08-28 | Aventis Pharma Deutschland Gmbh | Sulfonic acid sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds |
JP2004528319A (ja) * | 2001-03-30 | 2004-09-16 | ファイザー・プロダクツ・インク | ピリダジノンアルドースレダクダーゼ阻害物質 |
JP2009535335A (ja) * | 2006-04-26 | 2009-10-01 | ジェネンテック・インコーポレーテッド | ホスホイノシチド3−キナーゼ抑制剤化合物およびその使用方法 |
WO2010045017A1 (en) * | 2008-10-13 | 2010-04-22 | Janssen Pharmaceutica Nv | Amines and sulfoxides of thieno [2,3-d] pyrimidine and their use as adenosine a2a receptor antagonists |
WO2013158649A1 (en) * | 2012-04-16 | 2013-10-24 | Case Western Reserve University | Compositions and methods of modulating 15-pgdh activity |
JP6517197B2 (ja) * | 2013-10-15 | 2019-05-22 | ケース ウエスタン リザーブ ユニバーシティ | 短鎖デヒドロゲナーゼ活性を調節する組成物および方法 |
JP2018511581A (ja) * | 2015-03-08 | 2018-04-26 | ケース ウエスタン リザーブ ユニバーシティ | 線維症を処置するための短鎖デヒドロゲナーゼ活性阻害剤 |
JP2019078488A (ja) * | 2017-10-25 | 2019-05-23 | ダイキン工業株式会社 | 空気調和装置 |
Non-Patent Citations (5)
Title |
---|
DATABASE PUBCHEM COMPOUND [ONLINE] 12 JULY 2005, NCBI ACCESSION NO.1826991, JPN6020004867, ISSN: 0004210216 * |
DATABASE PUBCHEM COMPOUND [ONLINE] 7 SEPTEMBER 2005, NCBI ACCESSION NO.3337993, JPN6020004870, ISSN: 0004210217 * |
DATABASE PUBCHEM COMPOUND [ONLINE] 7 SEPTEMBER 2005, NCBI ACCESSION NO.3337995, JPN6020004875, ISSN: 0004210219 * |
DATABASE PUBCHEM COMPOUND [ONLINE] 7 SEPTEMBER 2005, NCBI ACCESSION NO.3337997, JPN6020004877, ISSN: 0004210220 * |
DATABASE PUBCHEM COMPOUND [ONLINE] 7 SEPTEMBER 2005, NCBI ACCESSION NO.3337998, JPN6020004872, ISSN: 0004210218 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11690847B2 (en) | 2016-11-30 | 2023-07-04 | Case Western Reserve University | Combinations of 15-PGDH inhibitors with corticosteroids and/or TNF inhibitors and uses thereof |
US11718589B2 (en) | 2017-02-06 | 2023-08-08 | Case Western Reserve University | Compositions and methods of modulating short-chain dehydrogenase |
Also Published As
Publication number | Publication date |
---|---|
US20180118756A1 (en) | 2018-05-03 |
US20240174688A1 (en) | 2024-05-30 |
CA2982784A1 (en) | 2016-10-20 |
CN108012528A (zh) | 2018-05-08 |
AU2016248080A1 (en) | 2017-11-02 |
EP3283074A1 (en) | 2018-02-21 |
HK1250651A1 (zh) | 2019-01-11 |
US20210094968A1 (en) | 2021-04-01 |
EP3283074A4 (en) | 2018-12-05 |
WO2016168472A1 (en) | 2016-10-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6789542B2 (ja) | 短鎖デヒドロゲナーゼ活性を調節する組成物および方法 | |
US20240174688A1 (en) | Compositions and methods of modulating short-chain dehydrogenase activity | |
US11718589B2 (en) | Compositions and methods of modulating short-chain dehydrogenase | |
US20240043440A1 (en) | Compositions and methods of modulating short-chain dehydrogenase activity | |
JP6203820B2 (ja) | 15−pgdh活性を調節する組成物および方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190415 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190415 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20200130 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200210 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20200507 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20200708 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20201020 |