KR102368159B1 - 폴리펩티드, 폴리펩티드 단편, 그의 유도체, 및 그의 적용 - Google Patents
폴리펩티드, 폴리펩티드 단편, 그의 유도체, 및 그의 적용 Download PDFInfo
- Publication number
- KR102368159B1 KR102368159B1 KR1020197028390A KR20197028390A KR102368159B1 KR 102368159 B1 KR102368159 B1 KR 102368159B1 KR 1020197028390 A KR1020197028390 A KR 1020197028390A KR 20197028390 A KR20197028390 A KR 20197028390A KR 102368159 B1 KR102368159 B1 KR 102368159B1
- Authority
- KR
- South Korea
- Prior art keywords
- seq
- polypeptide
- delete delete
- group
- amino acid
- 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.)
- Active
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 439
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 427
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 422
- 239000012634 fragment Substances 0.000 title abstract description 130
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 52
- 201000010099 disease Diseases 0.000 claims abstract description 48
- 230000003176 fibrotic effect Effects 0.000 claims abstract description 44
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 80
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims description 68
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 68
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 46
- 206010016654 Fibrosis Diseases 0.000 claims description 43
- 238000000034 method Methods 0.000 claims description 36
- 230000019491 signal transduction Effects 0.000 claims description 25
- 230000002685 pulmonary effect Effects 0.000 claims description 11
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 10
- 230000004913 activation Effects 0.000 claims description 9
- 208000001826 Marfan syndrome Diseases 0.000 claims description 8
- 238000002347 injection Methods 0.000 claims description 8
- 239000007924 injection Substances 0.000 claims description 8
- 208000002177 Cataract Diseases 0.000 claims description 7
- 201000009594 Systemic Scleroderma Diseases 0.000 claims description 7
- 206010042953 Systemic sclerosis Diseases 0.000 claims description 7
- 230000007882 cirrhosis Effects 0.000 claims description 7
- 206010036346 Posterior capsule opacification Diseases 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 201000002793 renal fibrosis Diseases 0.000 claims description 6
- 230000002792 vascular Effects 0.000 claims description 6
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 208000037803 restenosis Diseases 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 4
- 208000010412 Glaucoma Diseases 0.000 claims description 4
- 208000002260 Keloid Diseases 0.000 claims description 4
- 206010028594 Myocardial fibrosis Diseases 0.000 claims description 4
- 208000024248 Vascular System injury Diseases 0.000 claims description 4
- 208000012339 Vascular injury Diseases 0.000 claims description 4
- 238000002399 angioplasty Methods 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000001969 hypertrophic effect Effects 0.000 claims description 4
- 239000007943 implant Substances 0.000 claims description 4
- 238000011065 in-situ storage Methods 0.000 claims description 4
- 210000001117 keloid Anatomy 0.000 claims description 4
- 206010028537 myelofibrosis Diseases 0.000 claims description 4
- 201000000306 sarcoidosis Diseases 0.000 claims description 4
- 231100000241 scar Toxicity 0.000 claims description 4
- 238000007631 vascular surgery Methods 0.000 claims description 4
- 206010038934 Retinopathy proliferative Diseases 0.000 claims description 3
- 238000010521 absorption reaction Methods 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 claims description 3
- -1 inhalants Substances 0.000 claims description 3
- 238000010255 intramuscular injection Methods 0.000 claims description 3
- 239000007927 intramuscular injection Substances 0.000 claims description 3
- 239000011859 microparticle Substances 0.000 claims description 3
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 3
- 239000000843 powder Substances 0.000 claims description 3
- 208000032544 Cicatrix Diseases 0.000 claims description 2
- 239000000443 aerosol Substances 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims description 2
- 239000000227 bioadhesive Substances 0.000 claims description 2
- 239000006071 cream Substances 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000007884 disintegrant Substances 0.000 claims description 2
- 239000003623 enhancer Substances 0.000 claims description 2
- 239000000945 filler Substances 0.000 claims description 2
- 239000004088 foaming agent Substances 0.000 claims description 2
- 108020001507 fusion proteins Proteins 0.000 claims description 2
- 102000037865 fusion proteins Human genes 0.000 claims description 2
- 239000000499 gel Substances 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 239000000017 hydrogel Substances 0.000 claims description 2
- 239000007928 intraperitoneal injection Substances 0.000 claims description 2
- 238000001990 intravenous administration Methods 0.000 claims description 2
- 239000002502 liposome Substances 0.000 claims description 2
- 239000006210 lotion Substances 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 239000004530 micro-emulsion Substances 0.000 claims description 2
- 239000004005 microsphere Substances 0.000 claims description 2
- 239000002105 nanoparticle Substances 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000000049 pigment Substances 0.000 claims description 2
- 230000037387 scars Effects 0.000 claims description 2
- 238000001179 sorption measurement Methods 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- 238000010254 subcutaneous injection Methods 0.000 claims description 2
- 239000007929 subcutaneous injection Substances 0.000 claims description 2
- 239000004094 surface-active agent Substances 0.000 claims description 2
- 238000013268 sustained release Methods 0.000 claims description 2
- 239000012730 sustained-release form Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 239000000080 wetting agent Substances 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims 1
- 239000003889 eye drop Substances 0.000 claims 1
- 229940012356 eye drops Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 79
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 235000001014 amino acid Nutrition 0.000 description 162
- 241000700159 Rattus Species 0.000 description 150
- 210000004072 lung Anatomy 0.000 description 149
- 229940024606 amino acid Drugs 0.000 description 132
- 150000001413 amino acids Chemical class 0.000 description 126
- 210000001519 tissue Anatomy 0.000 description 123
- 230000004048 modification Effects 0.000 description 91
- 238000012986 modification Methods 0.000 description 91
- 238000011282 treatment Methods 0.000 description 83
- 230000037430 deletion Effects 0.000 description 75
- 238000012217 deletion Methods 0.000 description 75
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 73
- 210000004899 c-terminal region Anatomy 0.000 description 72
- 229940079593 drug Drugs 0.000 description 70
- 238000006467 substitution reaction Methods 0.000 description 68
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 65
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 59
- 239000002202 Polyethylene glycol Substances 0.000 description 57
- 229920001223 polyethylene glycol Polymers 0.000 description 57
- 241000282414 Homo sapiens Species 0.000 description 56
- 108010006654 Bleomycin Proteins 0.000 description 49
- 229960001561 bleomycin Drugs 0.000 description 49
- 238000007792 addition Methods 0.000 description 45
- 230000004761 fibrosis Effects 0.000 description 43
- 230000001575 pathological effect Effects 0.000 description 35
- 238000010171 animal model Methods 0.000 description 32
- 102000008186 Collagen Human genes 0.000 description 31
- 108010035532 Collagen Proteins 0.000 description 31
- 108090000623 proteins and genes Proteins 0.000 description 31
- 230000003902 lesion Effects 0.000 description 30
- 235000018102 proteins Nutrition 0.000 description 29
- 102000004169 proteins and genes Human genes 0.000 description 29
- UGZUVYDKAYNCII-ULQDDVLXSA-N Arg-Phe-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O UGZUVYDKAYNCII-ULQDDVLXSA-N 0.000 description 28
- 229920001436 collagen Polymers 0.000 description 28
- XOQYDFCQPWAMSA-KKHAAJSZSA-N Asn-Val-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XOQYDFCQPWAMSA-KKHAAJSZSA-N 0.000 description 25
- 230000002829 reductive effect Effects 0.000 description 25
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 23
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 23
- KWTVLKBOQATPHJ-SRVKXCTJSA-N Leu-Ala-Lys Chemical compound C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(C)C)N KWTVLKBOQATPHJ-SRVKXCTJSA-N 0.000 description 23
- WLDUCKSCDRIVLJ-NUMRIWBASA-N Thr-Gln-Asp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)O WLDUCKSCDRIVLJ-NUMRIWBASA-N 0.000 description 23
- 238000010253 intravenous injection Methods 0.000 description 23
- 108010009298 lysylglutamic acid Proteins 0.000 description 23
- PCBBLFVHTYNQGG-LAEOZQHASA-N Glu-Asn-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCC(=O)O)N PCBBLFVHTYNQGG-LAEOZQHASA-N 0.000 description 22
- QYSBJAUCUKHSLU-JYJNAYRXSA-N Tyr-Arg-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(O)=O QYSBJAUCUKHSLU-JYJNAYRXSA-N 0.000 description 22
- 230000006229 amino acid addition Effects 0.000 description 22
- 210000004969 inflammatory cell Anatomy 0.000 description 22
- IBIDRSSEHFLGSD-UHFFFAOYSA-N valinyl-arginine Natural products CC(C)C(N)C(=O)NC(C(O)=O)CCCN=C(N)N IBIDRSSEHFLGSD-UHFFFAOYSA-N 0.000 description 22
- MFMDKJIPHSWSBM-GUBZILKMSA-N Ala-Lys-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O MFMDKJIPHSWSBM-GUBZILKMSA-N 0.000 description 21
- 102100021277 Beta-secretase 2 Human genes 0.000 description 20
- 238000007385 chemical modification Methods 0.000 description 20
- 230000018109 developmental process Effects 0.000 description 20
- 238000011161 development Methods 0.000 description 19
- 230000014509 gene expression Effects 0.000 description 19
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 18
- 230000015572 biosynthetic process Effects 0.000 description 18
- 230000008021 deposition Effects 0.000 description 18
- 210000002744 extracellular matrix Anatomy 0.000 description 18
- 210000002950 fibroblast Anatomy 0.000 description 18
- 230000002757 inflammatory effect Effects 0.000 description 18
- 238000010186 staining Methods 0.000 description 18
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 17
- 230000000694 effects Effects 0.000 description 17
- 229960002591 hydroxyproline Drugs 0.000 description 17
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 17
- CYTSBCIIEHUPDU-ACZMJKKPSA-N Gln-Asp-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O CYTSBCIIEHUPDU-ACZMJKKPSA-N 0.000 description 16
- 239000006166 lysate Substances 0.000 description 16
- 230000002265 prevention Effects 0.000 description 16
- 238000001514 detection method Methods 0.000 description 15
- 230000008595 infiltration Effects 0.000 description 15
- 238000001764 infiltration Methods 0.000 description 15
- 210000000651 myofibroblast Anatomy 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 15
- IVXJODPZRWHCCR-JYJNAYRXSA-N Val-Arg-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N IVXJODPZRWHCCR-JYJNAYRXSA-N 0.000 description 14
- 108010005233 alanylglutamic acid Proteins 0.000 description 14
- 238000011156 evaluation Methods 0.000 description 14
- 108010073101 phenylalanylleucine Proteins 0.000 description 14
- 239000002504 physiological saline solution Substances 0.000 description 14
- 206010001889 Alveolitis Diseases 0.000 description 13
- 101710150190 Beta-secretase 2 Proteins 0.000 description 13
- 102000004127 Cytokines Human genes 0.000 description 13
- 108090000695 Cytokines Proteins 0.000 description 13
- 201000001155 extrinsic allergic alveolitis Diseases 0.000 description 13
- 208000022098 hypersensitivity pneumonitis Diseases 0.000 description 13
- 230000035755 proliferation Effects 0.000 description 13
- 108010008685 alanyl-glutamyl-aspartic acid Proteins 0.000 description 12
- 150000004665 fatty acids Chemical class 0.000 description 12
- 231100000915 pathological change Toxicity 0.000 description 12
- 230000036285 pathological change Effects 0.000 description 12
- 230000006378 damage Effects 0.000 description 11
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 11
- 210000000056 organ Anatomy 0.000 description 11
- 206010035664 Pneumonia Diseases 0.000 description 10
- 235000014113 dietary fatty acids Nutrition 0.000 description 10
- 229930195729 fatty acid Natural products 0.000 description 10
- 239000000194 fatty acid Substances 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 230000001225 therapeutic effect Effects 0.000 description 10
- 102000012422 Collagen Type I Human genes 0.000 description 9
- 108010022452 Collagen Type I Proteins 0.000 description 9
- 230000037396 body weight Effects 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 230000007423 decrease Effects 0.000 description 9
- 238000006206 glycosylation reaction Methods 0.000 description 9
- 108010005652 splenotritin Proteins 0.000 description 9
- 230000008719 thickening Effects 0.000 description 9
- MUWDILPCTSMUHI-ZLUOBGJFSA-N Asp-Asn-Cys Chemical compound C([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N)C(=O)O MUWDILPCTSMUHI-ZLUOBGJFSA-N 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 8
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- 210000003734 kidney Anatomy 0.000 description 8
- 229960004378 nintedanib Drugs 0.000 description 8
- XZXHXSATPCNXJR-ZIADKAODSA-N nintedanib Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=CC=CC=1)\NC(C=C1)=CC=C1N(C)C(=O)CN1CCN(C)CC1 XZXHXSATPCNXJR-ZIADKAODSA-N 0.000 description 8
- KXEVYGKATAMXJJ-ACZMJKKPSA-N Ala-Glu-Asp Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O KXEVYGKATAMXJJ-ACZMJKKPSA-N 0.000 description 7
- CVXXSWQORBZAAA-SRVKXCTJSA-N Arg-Lys-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCN=C(N)N CVXXSWQORBZAAA-SRVKXCTJSA-N 0.000 description 7
- 102100037362 Fibronectin Human genes 0.000 description 7
- 108010067306 Fibronectins Proteins 0.000 description 7
- NTBDVNJIWCKURJ-ACZMJKKPSA-N Glu-Asp-Asn Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NTBDVNJIWCKURJ-ACZMJKKPSA-N 0.000 description 7
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 230000002159 abnormal effect Effects 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 230000001684 chronic effect Effects 0.000 description 7
- 230000013595 glycosylation Effects 0.000 description 7
- 210000002216 heart Anatomy 0.000 description 7
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 7
- 210000002540 macrophage Anatomy 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 230000026683 transduction Effects 0.000 description 7
- 238000010361 transduction Methods 0.000 description 7
- 206010002091 Anaesthesia Diseases 0.000 description 6
- 102100035631 Bloom syndrome protein Human genes 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
- 230000037005 anaesthesia Effects 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 238000001647 drug administration Methods 0.000 description 6
- 230000007705 epithelial mesenchymal transition Effects 0.000 description 6
- 125000000524 functional group Chemical group 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- 238000001543 one-way ANOVA Methods 0.000 description 6
- 230000007170 pathology Effects 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 238000011552 rat model Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- 101150091877 Ccn2 gene Proteins 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 5
- 102000003816 Interleukin-13 Human genes 0.000 description 5
- 108090000176 Interleukin-13 Proteins 0.000 description 5
- VFDRDMOMHBJGKD-UFYCRDLUSA-N Phe-Tyr-Arg Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N VFDRDMOMHBJGKD-UFYCRDLUSA-N 0.000 description 5
- 230000021736 acetylation Effects 0.000 description 5
- 238000006640 acetylation reaction Methods 0.000 description 5
- 230000009435 amidation Effects 0.000 description 5
- 238000007112 amidation reaction Methods 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 210000002808 connective tissue Anatomy 0.000 description 5
- 230000007850 degeneration Effects 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000000835 fiber Substances 0.000 description 5
- 210000003494 hepatocyte Anatomy 0.000 description 5
- 238000002715 modification method Methods 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 210000000952 spleen Anatomy 0.000 description 5
- 125000003396 thiol group Chemical group [H]S* 0.000 description 5
- 210000003462 vein Anatomy 0.000 description 5
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 4
- ICAYWNTWHRRAQP-FXQIFTODSA-N Asp-Arg-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)O)N)CN=C(N)N ICAYWNTWHRRAQP-FXQIFTODSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102000019034 Chemokines Human genes 0.000 description 4
- 108010012236 Chemokines Proteins 0.000 description 4
- 102000015225 Connective Tissue Growth Factor Human genes 0.000 description 4
- 108010039419 Connective Tissue Growth Factor Proteins 0.000 description 4
- FYYSIASRLDJUNP-WHFBIAKZSA-N Glu-Asp Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(O)=O FYYSIASRLDJUNP-WHFBIAKZSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 208000037273 Pathologic Processes Diseases 0.000 description 4
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 4
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 4
- 238000005903 acid hydrolysis reaction Methods 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 230000003444 anaesthetic effect Effects 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 210000001185 bone marrow Anatomy 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 208000018631 connective tissue disease Diseases 0.000 description 4
- 230000002354 daily effect Effects 0.000 description 4
- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 239000003607 modifier Substances 0.000 description 4
- 210000000440 neutrophil Anatomy 0.000 description 4
- 230000009054 pathological process Effects 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- ISWRGOKTTBVCFA-UHFFFAOYSA-N pirfenidone Chemical compound C1=C(C)C=CC(=O)N1C1=CC=CC=C1 ISWRGOKTTBVCFA-UHFFFAOYSA-N 0.000 description 4
- 229960003073 pirfenidone Drugs 0.000 description 4
- 210000004224 pleura Anatomy 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 230000037390 scarring Effects 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 230000004584 weight gain Effects 0.000 description 4
- 235000019786 weight gain Nutrition 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 3
- 206010067484 Adverse reaction Diseases 0.000 description 3
- QMQZYILAWUOLPV-JYJNAYRXSA-N Arg-Tyr-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)CC1=CC=C(O)C=C1 QMQZYILAWUOLPV-JYJNAYRXSA-N 0.000 description 3
- QUMKPKWYDVMGNT-NUMRIWBASA-N Asn-Thr-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N)O QUMKPKWYDVMGNT-NUMRIWBASA-N 0.000 description 3
- XEDQMTWEYFBOIK-ACZMJKKPSA-N Asp-Ala-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O XEDQMTWEYFBOIK-ACZMJKKPSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- BTSPOOHJBYJRKO-CIUDSAMLSA-N Gln-Asp-Arg Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O BTSPOOHJBYJRKO-CIUDSAMLSA-N 0.000 description 3
- 101710088172 HTH-type transcriptional regulator RipA Proteins 0.000 description 3
- 206010020880 Hypertrophy Diseases 0.000 description 3
- 208000029523 Interstitial Lung disease Diseases 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000004989 O-glycosylation Effects 0.000 description 3
- 229930040373 Paraformaldehyde Natural products 0.000 description 3
- 206010038848 Retinal detachment Diseases 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
- 230000006838 adverse reaction Effects 0.000 description 3
- 108010013835 arginine glutamate Proteins 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 230000006866 deterioration Effects 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 210000001508 eye Anatomy 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 210000004704 glottis Anatomy 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 230000035876 healing Effects 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000028709 inflammatory response Effects 0.000 description 3
- 230000010534 mechanism of action Effects 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 210000000214 mouth Anatomy 0.000 description 3
- 239000012188 paraffin wax Substances 0.000 description 3
- 229920002866 paraformaldehyde Polymers 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 238000010814 radioimmunoprecipitation assay Methods 0.000 description 3
- 238000003753 real-time PCR Methods 0.000 description 3
- 230000008439 repair process Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 229940126585 therapeutic drug Drugs 0.000 description 3
- 210000003437 trachea Anatomy 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 108020004463 18S ribosomal RNA Proteins 0.000 description 2
- XACXDSRQIXRMNS-OLHMAJIHSA-N Asp-Asn-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)O)N)O XACXDSRQIXRMNS-OLHMAJIHSA-N 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 208000006386 Bone Resorption Diseases 0.000 description 2
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 102000003951 Erythropoietin Human genes 0.000 description 2
- 108090000394 Erythropoietin Proteins 0.000 description 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 2
- 108091008794 FGF receptors Proteins 0.000 description 2
- 102100031509 Fibrillin-1 Human genes 0.000 description 2
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 2
- VAZZOGXDUQSVQF-NUMRIWBASA-N Glu-Asn-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCC(=O)O)N)O VAZZOGXDUQSVQF-NUMRIWBASA-N 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 206010019668 Hepatic fibrosis Diseases 0.000 description 2
- 101000846893 Homo sapiens Fibrillin-1 Proteins 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- YOZCKMXHBYKOMQ-IHRRRGAJSA-N Leu-Arg-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)O)N YOZCKMXHBYKOMQ-IHRRRGAJSA-N 0.000 description 2
- 206010067125 Liver injury Diseases 0.000 description 2
- 208000019693 Lung disease Diseases 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 102000005741 Metalloproteases Human genes 0.000 description 2
- 108010006035 Metalloproteases Proteins 0.000 description 2
- 230000004988 N-glycosylation Effects 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 108091008606 PDGF receptors Proteins 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 2
- 206010037423 Pulmonary oedema Diseases 0.000 description 2
- 206010039710 Scleroderma Diseases 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 206010050207 Skin fibrosis Diseases 0.000 description 2
- 206010040867 Skin hypertrophy Diseases 0.000 description 2
- 102000007374 Smad Proteins Human genes 0.000 description 2
- 108010007945 Smad Proteins Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 210000004241 Th2 cell Anatomy 0.000 description 2
- XHALUUQSNXSPLP-UFYCRDLUSA-N Tyr-Arg-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 XHALUUQSNXSPLP-UFYCRDLUSA-N 0.000 description 2
- 108091008605 VEGF receptors Proteins 0.000 description 2
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 210000001132 alveolar macrophage Anatomy 0.000 description 2
- 150000001408 amides Chemical group 0.000 description 2
- 230000003367 anti-collagen effect Effects 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 238000003149 assay kit Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 108091008324 binding proteins Proteins 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 230000024279 bone resorption Effects 0.000 description 2
- 210000000748 cardiovascular system Anatomy 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000005779 cell damage Effects 0.000 description 2
- 208000037887 cell injury Diseases 0.000 description 2
- 230000004709 cell invasion Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 208000037976 chronic inflammation Diseases 0.000 description 2
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 2
- 208000020832 chronic kidney disease Diseases 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 230000007783 downstream signaling Effects 0.000 description 2
- 239000003596 drug target Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000007071 enzymatic hydrolysis Effects 0.000 description 2
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 2
- 229940105423 erythropoietin Drugs 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 210000003414 extremity Anatomy 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 150000004676 glycans Polymers 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 230000003394 haemopoietic effect Effects 0.000 description 2
- 230000023597 hemostasis Effects 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- 230000009610 hypersensitivity Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000004410 intraocular pressure Effects 0.000 description 2
- 230000009545 invasion Effects 0.000 description 2
- 210000001503 joint Anatomy 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 230000004199 lung function Effects 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 150000002772 monosaccharides Chemical class 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 208000031225 myocardial ischemia Diseases 0.000 description 2
- 210000004498 neuroglial cell Anatomy 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229920001542 oligosaccharide Polymers 0.000 description 2
- 150000002482 oligosaccharides Chemical class 0.000 description 2
- 230000004768 organ dysfunction Effects 0.000 description 2
- 229940000673 orphan drug Drugs 0.000 description 2
- 239000002859 orphan drug Substances 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 208000005333 pulmonary edema Diseases 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 238000007634 remodeling Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000012827 research and development Methods 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 210000000844 retinal pigment epithelial cell Anatomy 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 150000004671 saturated fatty acids Chemical class 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000003393 splenic effect Effects 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 210000000115 thoracic cavity Anatomy 0.000 description 2
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 210000001585 trabecular meshwork Anatomy 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 210000004926 tubular epithelial cell Anatomy 0.000 description 2
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 2
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 2
- 229940124676 vascular endothelial growth factor receptor Drugs 0.000 description 2
- 210000001835 viscera Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000033116 Asbestos intoxication Diseases 0.000 description 1
- VGRHZPNRCLAHQA-IMJSIDKUSA-N Asp-Asn Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(N)=O)C(O)=O VGRHZPNRCLAHQA-IMJSIDKUSA-N 0.000 description 1
- 201000004569 Blindness 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
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 102000005600 Cathepsins Human genes 0.000 description 1
- 108010084457 Cathepsins Proteins 0.000 description 1
- 108090000738 Decorin Proteins 0.000 description 1
- 102000004237 Decorin Human genes 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 1
- FLLRAEJOLZPSMN-CIUDSAMLSA-N Glu-Asn-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N FLLRAEJOLZPSMN-CIUDSAMLSA-N 0.000 description 1
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 1
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 description 1
- 101000788682 Homo sapiens GATA-type zinc finger protein 1 Proteins 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 102000012355 Integrin beta1 Human genes 0.000 description 1
- 108010022222 Integrin beta1 Proteins 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 206010024214 Lenticular opacities Diseases 0.000 description 1
- 241000880493 Leptailurus serval Species 0.000 description 1
- YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 description 1
- 108010019598 Liraglutide Proteins 0.000 description 1
- 208000032376 Lung infection Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- ZXEUFAVXODIPHC-GUBZILKMSA-N Lys-Glu-Asn Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O ZXEUFAVXODIPHC-GUBZILKMSA-N 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 229920001410 Microfiber Polymers 0.000 description 1
- 102100025751 Mothers against decapentaplegic homolog 2 Human genes 0.000 description 1
- 101710143123 Mothers against decapentaplegic homolog 2 Proteins 0.000 description 1
- 102100025748 Mothers against decapentaplegic homolog 3 Human genes 0.000 description 1
- 101710143111 Mothers against decapentaplegic homolog 3 Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 208000014767 Myeloproliferative disease Diseases 0.000 description 1
- 235000021360 Myristic acid Nutrition 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 206010034972 Photosensitivity reaction Diseases 0.000 description 1
- 102100023347 Proto-oncogene tyrosine-protein kinase ROS Human genes 0.000 description 1
- 206010056342 Pulmonary mass Diseases 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- 206010039580 Scar Diseases 0.000 description 1
- FUMGHWDRRFCKEP-CIUDSAMLSA-N Ser-Leu-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O FUMGHWDRRFCKEP-CIUDSAMLSA-N 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- 201000010001 Silicosis Diseases 0.000 description 1
- 102000011117 Transforming Growth Factor beta2 Human genes 0.000 description 1
- 101800000304 Transforming growth factor beta-2 Proteins 0.000 description 1
- 102000056172 Transforming growth factor beta-3 Human genes 0.000 description 1
- 108090000097 Transforming growth factor beta-3 Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 206010064390 Tumour invasion Diseases 0.000 description 1
- IIJWXEUNETVJPV-IHRRRGAJSA-N Tyr-Arg-Ser Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(=O)O)N)O IIJWXEUNETVJPV-IHRRRGAJSA-N 0.000 description 1
- UQMPYVLTQCGRSK-IFFSRLJSSA-N Val-Thr-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N)O UQMPYVLTQCGRSK-IFFSRLJSSA-N 0.000 description 1
- 206010047555 Visual field defect Diseases 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000000397 acetylating effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 230000009798 acute exacerbation Effects 0.000 description 1
- 206010069351 acute lung injury Diseases 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 210000002821 alveolar epithelial cell Anatomy 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000003510 anti-fibrotic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 208000007474 aortic aneurysm Diseases 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 210000001742 aqueous humor Anatomy 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 210000001188 articular cartilage Anatomy 0.000 description 1
- 206010003441 asbestosis Diseases 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical class [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000002798 bone marrow cell Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 230000009400 cancer invasion Effects 0.000 description 1
- 150000001720 carbohydrates Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 210000001054 cardiac fibroblast Anatomy 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 231100000012 chronic liver injury Toxicity 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000002281 colonystimulating effect Effects 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 210000001951 dura mater Anatomy 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 208000037888 epithelial cell injury Diseases 0.000 description 1
- 230000008556 epithelial cell proliferation Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 210000003499 exocrine gland Anatomy 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 230000003352 fibrogenic effect Effects 0.000 description 1
- 230000009795 fibrotic process Effects 0.000 description 1
- 210000003811 finger Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000024924 glomerular filtration Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 229930004094 glycosylphosphatidylinositol Natural products 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
- 210000001983 hard palate Anatomy 0.000 description 1
- 201000000615 hard palate cancer Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 229920006158 high molecular weight polymer Polymers 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000037417 hyperactivation Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 230000009390 immune abnormality Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000006749 inflammatory damage Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000008798 inflammatory stress Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 238000005184 irreversible process Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 210000001542 lens epithelial cell Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229960002701 liraglutide Drugs 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 231100001252 long-term toxicity Toxicity 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 231100000142 low-dose toxicity Toxicity 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 210000003593 megakaryocyte Anatomy 0.000 description 1
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 239000003658 microfiber Substances 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 230000008692 neointimal formation Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 238000011457 non-pharmacological treatment Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000037311 normal skin Effects 0.000 description 1
- 230000001473 noxious effect Effects 0.000 description 1
- 208000030212 nutrition disease Diseases 0.000 description 1
- 208000019180 nutritional disease Diseases 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000000771 oncological effect Effects 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- 150000002943 palmitic acids Chemical class 0.000 description 1
- 210000004738 parenchymal cell Anatomy 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000036211 photosensitivity Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 230000030716 positive regulation of phosphorylation Effects 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 208000010707 pulmonary consolidation Diseases 0.000 description 1
- 208000008128 pulmonary tuberculosis Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003762 quantitative reverse transcription PCR Methods 0.000 description 1
- 102000010838 rac1 GTP Binding Protein Human genes 0.000 description 1
- 108010062302 rac1 GTP Binding Protein Proteins 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000005084 renal tissue Anatomy 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000004264 retinal detachment Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 208000019793 rhegmatogenous retinal detachment Diseases 0.000 description 1
- 230000036573 scar formation Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000011894 semi-preparative HPLC Methods 0.000 description 1
- 238000012764 semi-quantitative analysis Methods 0.000 description 1
- 238000012206 semi-quantitative assay Methods 0.000 description 1
- 208000037974 severe injury Diseases 0.000 description 1
- 230000009528 severe injury Effects 0.000 description 1
- 230000037380 skin damage Effects 0.000 description 1
- 210000001626 skin fibroblast Anatomy 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 230000029547 smooth muscle hypertrophy Effects 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 210000005065 subchondral bone plate Anatomy 0.000 description 1
- 210000002301 subretinal fluid Anatomy 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 210000005222 synovial tissue Anatomy 0.000 description 1
- 201000004595 synovitis Diseases 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 230000007838 tissue remodeling Effects 0.000 description 1
- 210000003371 toe Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 231100000155 toxicity by organ Toxicity 0.000 description 1
- 230000007675 toxicity by organ Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 210000004127 vitreous body Anatomy 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000010388 wound contraction Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/10—Peptides having 12 to 20 amino acids
-
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pulmonology (AREA)
- Physical Education & Sports Medicine (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710115604.4A CN106860855B (zh) | 2017-03-01 | 2017-03-01 | 多肽及多肽衍生物在预防和治疗纤维化疾病中的应用 |
| CN201710115604.4 | 2017-03-01 | ||
| CN201710677602.4A CN109384830B (zh) | 2017-08-09 | 2017-08-09 | 多肽、多肽片段及其衍生物在防治纤维化疾病中的应用 |
| CN201710677602.4 | 2017-08-09 | ||
| PCT/CN2018/077492 WO2018157807A1 (zh) | 2017-03-01 | 2018-02-28 | 多肽、多肽片段及其衍生物与应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20190125373A KR20190125373A (ko) | 2019-11-06 |
| KR102368159B1 true KR102368159B1 (ko) | 2022-03-03 |
Family
ID=63369746
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020197028390A Active KR102368159B1 (ko) | 2017-03-01 | 2018-02-28 | 폴리펩티드, 폴리펩티드 단편, 그의 유도체, 및 그의 적용 |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US12011475B2 (enExample) |
| EP (1) | EP3590527A4 (enExample) |
| JP (1) | JP6965362B2 (enExample) |
| KR (1) | KR102368159B1 (enExample) |
| AU (1) | AU2018227737B2 (enExample) |
| CA (1) | CA3054839C (enExample) |
| IL (1) | IL268971B2 (enExample) |
| SG (1) | SG11201907914QA (enExample) |
| WO (1) | WO2018157807A1 (enExample) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HUE065418T2 (hu) * | 2015-10-27 | 2024-05-28 | Univ Taipei Medical | Indolin származékok fibrózisos betegségek kezelésére és/vagy megelõzésére |
| CN112386678B (zh) * | 2019-08-13 | 2023-07-07 | 成都惠泰生物医药有限公司 | 多肽或其衍生物的应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996036349A1 (en) | 1995-05-17 | 1996-11-21 | Manitoba Cancer Treatment And Research Foundation | POST-TRANSLATIONAL ACTIVATION OF TGF-β1 INVOLVING THE TSP-1 RECEPTOR CD36 |
| WO2009043525A2 (en) | 2007-09-11 | 2009-04-09 | Mondobiotech Laboratories Ag | Use of the combination of gluten exorphin c and cd36 as a therapeutic agent |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7601691B2 (en) | 1999-05-17 | 2009-10-13 | Conjuchem Biotechnologies Inc. | Anti-obesity agents |
| EP1105409B1 (en) | 1999-05-17 | 2006-03-01 | Conjuchem, Inc. | Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components |
| BR0207310A (pt) | 2001-12-18 | 2004-08-17 | Mondobiotech Sa | Composição farmacêutica de interferon gama ou de pirfenidona com diagnósticos moleculares para o melhor tratamento de doenças pulmonares intersticiais |
| EP2197469A2 (en) | 2007-09-11 | 2010-06-23 | Mondobiotech Laboratories AG | Use of nf-kappab inhibitor sn50 and optionally angiotensin iii as therapeutic agents in the treatment of eg hbv infection |
| WO2012069511A1 (en) * | 2010-11-24 | 2012-05-31 | F. Hoffmann-La Roche Ag | Methods for detecting low grade inflammation |
| HRP20211582T1 (hr) | 2011-06-03 | 2022-01-07 | Xoma Technology Ltd. | Protutijela specifična za tgf-beta |
| WO2016054114A1 (en) | 2014-09-29 | 2016-04-07 | The Regents Of The University Of California | Compositions for expanding regulatory t cells (treg), and treating autoimmune and inflammatory diseases and conditions |
| CN104313028A (zh) | 2014-09-30 | 2015-01-28 | 北京生科东方科技有限公司 | 抗类风湿关节炎的小肽基因及其生产方法 |
| CN105061600A (zh) | 2015-09-05 | 2015-11-18 | 苏州普罗达生物科技有限公司 | 类风湿因子IgA抑制多肽及其应用 |
| CN106860855B (zh) * | 2017-03-01 | 2021-06-11 | 成都惠泰生物医药有限公司 | 多肽及多肽衍生物在预防和治疗纤维化疾病中的应用 |
-
2018
- 2018-02-28 JP JP2019548059A patent/JP6965362B2/ja active Active
- 2018-02-28 CA CA3054839A patent/CA3054839C/en active Active
- 2018-02-28 SG SG11201907914QA patent/SG11201907914QA/en unknown
- 2018-02-28 IL IL268971A patent/IL268971B2/en unknown
- 2018-02-28 WO PCT/CN2018/077492 patent/WO2018157807A1/zh not_active Ceased
- 2018-02-28 AU AU2018227737A patent/AU2018227737B2/en active Active
- 2018-02-28 EP EP18760361.8A patent/EP3590527A4/en active Pending
- 2018-02-28 US US16/490,543 patent/US12011475B2/en active Active
- 2018-02-28 KR KR1020197028390A patent/KR102368159B1/ko active Active
-
2024
- 2024-05-07 US US18/656,641 patent/US20240390450A1/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996036349A1 (en) | 1995-05-17 | 1996-11-21 | Manitoba Cancer Treatment And Research Foundation | POST-TRANSLATIONAL ACTIVATION OF TGF-β1 INVOLVING THE TSP-1 RECEPTOR CD36 |
| WO2009043525A2 (en) | 2007-09-11 | 2009-04-09 | Mondobiotech Laboratories Ag | Use of the combination of gluten exorphin c and cd36 as a therapeutic agent |
Non-Patent Citations (2)
| Title |
|---|
| Am. J. Respir. Cell Mol. Biol., Vol. 23, No. 2, pp. 204-212(2000.08.01.) |
| Biochim. Biophys. Acta., Vol. 1852, No. 7, pp. 1323-1333(2015.07.) |
Also Published As
| Publication number | Publication date |
|---|---|
| CA3054839A1 (en) | 2018-09-07 |
| EP3590527A4 (en) | 2021-01-06 |
| KR20190125373A (ko) | 2019-11-06 |
| JP6965362B2 (ja) | 2021-11-10 |
| EP3590527A1 (en) | 2020-01-08 |
| AU2018227737B2 (en) | 2021-04-01 |
| IL268971B2 (en) | 2024-01-01 |
| IL268971B1 (en) | 2023-09-01 |
| WO2018157807A1 (zh) | 2018-09-07 |
| AU2018227737A1 (en) | 2019-10-17 |
| CA3054839C (en) | 2023-08-29 |
| AU2018227737A2 (en) | 2020-01-30 |
| IL268971A (en) | 2019-10-31 |
| JP2020509061A (ja) | 2020-03-26 |
| US20240390450A1 (en) | 2024-11-28 |
| US20220072082A1 (en) | 2022-03-10 |
| SG11201907914QA (en) | 2019-09-27 |
| US12011475B2 (en) | 2024-06-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106860855B (zh) | 多肽及多肽衍生物在预防和治疗纤维化疾病中的应用 | |
| CN109384830B (zh) | 多肽、多肽片段及其衍生物在防治纤维化疾病中的应用 | |
| US20240390450A1 (en) | Polypeptide, polypeptide fragment, derivative thereof, and applications thereof | |
| JP7597398B2 (ja) | 組換え神経成長因子のための組成物及び方法 | |
| Qi et al. | Tissue inhibitor of metalloproteinases-3 peptides inhibit angiogenesis and choroidal neovascularization in mice | |
| EP2552470B1 (en) | Peptides for promoting angiogenesis and an use thereof | |
| CA2371241A1 (en) | Tgf-.alpha. polypeptides, functional fragments and methods of use therefor | |
| KR102023058B1 (ko) | 이중 이온 pH-민감성 공중합체를 이용한 허혈성 뇌질환 치료용 약물 전달체 | |
| KR20150140686A (ko) | 신증후군 및 관련 병태의 치료 방법 | |
| US20130085108A1 (en) | Peptides for promoting angiogenesis and an use thereof | |
| KR20200138798A (ko) | C-말단 cdnf 단편, 이를 포함하는 약학적 조성물 및 그 용도 | |
| HK40015944A (en) | Polypeptide, polypeptide fragment, derivative thereof, and applications thereof | |
| JP2013253079A (ja) | 生物学的に活性なヒト尿中トリプシンインヒビターのＦｃ融合タンパク質並びにその調製および使用 | |
| US20230303646A1 (en) | Analogs of human fibroblast growth factors | |
| CN101503458B (zh) | 预防和治疗血管新生的小分子多肽及其应用 | |
| CN101730710A (zh) | Vegf-d突变体及其用途 | |
| US20110092427A1 (en) | Polypeptide and pharmaceutical composition containing the polypeptide | |
| US20250263456A1 (en) | Use of fgf5 transcript variant-2 and protein thereof in preventing, inhibiting, or treating liver fibrosis | |
| Liu et al. | Bioactive nanofiber hydrogel acts on VEGF and VEGF receptor to unleash inhibition effects on corneal neovascularization | |
| EP4032901A1 (en) | Recombinant human neuregulin derivatives and use thereof | |
| WO2025096630A2 (en) | Collagen peptide-based medicament compositions and uses thereof | |
| JP2000086533A (ja) | 新規なアレルギー治療剤 | |
| Qi et al. | Tissue Inhibitor of Metalloproteinases-3 Peptides Inhibit Angiogenesis and Choroidal | |
| AU2005201473A1 (en) | TGF-alpha polypeptides, functional fragments and methods of use therefor | |
| HK1147502A (en) | Polypeptide and pharmaceutical composition containing the polypeptide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20190926 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20191016 Comment text: Request for Examination of Application |
|
| PG1501 | Laying open of application | ||
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20210312 Patent event code: PE09021S01D |
|
| E90F | Notification of reason for final refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Final Notice of Reason for Refusal Patent event date: 20210726 Patent event code: PE09021S02D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20211128 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20220223 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20220224 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration | ||
| PR1001 | Payment of annual fee |
Payment date: 20250219 Start annual number: 4 End annual number: 4 |