JP2006516287A - Ｍｎｔｆペプチドおよび組成物ならびに使用の方法 - Google Patents
Ｍｎｔｆペプチドおよび組成物ならびに使用の方法 Download PDFInfo
- Publication number
- JP2006516287A JP2006516287A JP2006501057A JP2006501057A JP2006516287A JP 2006516287 A JP2006516287 A JP 2006516287A JP 2006501057 A JP2006501057 A JP 2006501057A JP 2006501057 A JP2006501057 A JP 2006501057A JP 2006516287 A JP2006516287 A JP 2006516287A
- Authority
- JP
- Japan
- Prior art keywords
- seq
- peptide
- peptide analog
- motor
- 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.)
- Withdrawn
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 170
- 238000000034 method Methods 0.000 title claims abstract description 38
- 239000000203 mixture Substances 0.000 title claims abstract description 30
- 102000004196 processed proteins & peptides Human genes 0.000 title abstract description 52
- 108010025020 Nerve Growth Factor Proteins 0.000 claims abstract description 39
- 210000002569 neuron Anatomy 0.000 claims abstract description 37
- 102000007072 Nerve Growth Factors Human genes 0.000 claims abstract description 22
- 239000003900 neurotrophic factor Substances 0.000 claims abstract description 22
- 230000035899 viability Effects 0.000 claims abstract description 17
- 230000000508 neurotrophic effect Effects 0.000 claims abstract description 7
- 210000002161 motor neuron Anatomy 0.000 claims description 55
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 27
- 125000000539 amino acid group Chemical group 0.000 claims description 23
- 210000003205 muscle Anatomy 0.000 claims description 20
- 238000000338 in vitro Methods 0.000 claims description 19
- 108090000623 proteins and genes Proteins 0.000 claims description 19
- 102000004169 proteins and genes Human genes 0.000 claims description 18
- 150000001413 amino acids Chemical class 0.000 claims description 17
- 238000001727 in vivo Methods 0.000 claims description 16
- 230000004663 cell proliferation Effects 0.000 claims description 15
- 230000012010 growth Effects 0.000 claims description 14
- 210000005036 nerve Anatomy 0.000 claims description 14
- 230000008929 regeneration Effects 0.000 claims description 14
- 238000011069 regeneration method Methods 0.000 claims description 14
- 210000003050 axon Anatomy 0.000 claims description 13
- 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 12
- 239000012634 fragment Substances 0.000 claims description 12
- 102000037865 fusion proteins Human genes 0.000 claims description 12
- 108020001507 fusion proteins Proteins 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 11
- 208000027418 Wounds and injury Diseases 0.000 claims description 9
- 239000007787 solid Substances 0.000 claims description 9
- 210000000278 spinal cord Anatomy 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 7
- 230000007832 reinnervation Effects 0.000 claims description 7
- 210000002950 fibroblast Anatomy 0.000 claims description 6
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 6
- 238000006467 substitution reaction Methods 0.000 claims description 6
- 206010052428 Wound Diseases 0.000 claims description 5
- 230000003376 axonal effect Effects 0.000 claims description 5
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 5
- 230000007850 degeneration Effects 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 230000004770 neurodegeneration Effects 0.000 claims description 4
- 231100000241 scar Toxicity 0.000 claims description 4
- 210000004116 schwann cell Anatomy 0.000 claims description 4
- 208000010886 Peripheral nerve injury Diseases 0.000 claims description 3
- 230000006907 apoptotic process Effects 0.000 claims description 3
- 210000004969 inflammatory cell Anatomy 0.000 claims description 3
- 230000029663 wound healing Effects 0.000 claims description 3
- 102000014914 Carrier Proteins Human genes 0.000 claims description 2
- 108010078791 Carrier Proteins Proteins 0.000 claims description 2
- 210000004698 lymphocyte Anatomy 0.000 claims description 2
- 210000002540 macrophage Anatomy 0.000 claims description 2
- 230000005012 migration Effects 0.000 claims description 2
- 238000013508 migration Methods 0.000 claims description 2
- 230000002232 neuromuscular Effects 0.000 claims description 2
- 239000002245 particle Substances 0.000 claims description 2
- 239000000562 conjugate Substances 0.000 claims 2
- 208000004296 neuralgia Diseases 0.000 claims 2
- 208000021722 neuropathic pain Diseases 0.000 claims 2
- 230000008595 infiltration Effects 0.000 claims 1
- 238000001764 infiltration Methods 0.000 claims 1
- 108010091748 peptide A Proteins 0.000 claims 1
- 239000000863 peptide conjugate Substances 0.000 claims 1
- 230000002093 peripheral effect Effects 0.000 claims 1
- 230000009772 tissue formation Effects 0.000 claims 1
- 230000035755 proliferation Effects 0.000 abstract description 25
- 108020001580 protein domains Proteins 0.000 abstract description 5
- 230000009471 action Effects 0.000 abstract description 4
- 230000001537 neural effect Effects 0.000 abstract description 3
- 101000663429 Drosophila melanogaster Neurotrophin 1 Proteins 0.000 abstract description 2
- 230000002981 neuropathic effect Effects 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 47
- 229920001184 polypeptide Polymers 0.000 description 19
- 241000700159 Rattus Species 0.000 description 18
- 235000001014 amino acid Nutrition 0.000 description 17
- 235000018102 proteins Nutrition 0.000 description 17
- 230000000694 effects Effects 0.000 description 16
- 206010029260 Neuroblastoma Diseases 0.000 description 15
- 102000007079 Peptide Fragments Human genes 0.000 description 15
- 108010033276 Peptide Fragments Proteins 0.000 description 15
- 229940024606 amino acid Drugs 0.000 description 14
- 238000003556 assay Methods 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 230000004044 response Effects 0.000 description 10
- -1 aromatic diazonium compounds Chemical class 0.000 description 9
- 230000001965 increasing effect Effects 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 230000007423 decrease Effects 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 230000004071 biological effect Effects 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 210000003099 femoral nerve Anatomy 0.000 description 7
- 230000004083 survival effect Effects 0.000 description 7
- 102000001708 Protein Isoforms Human genes 0.000 description 6
- 108010029485 Protein Isoforms Proteins 0.000 description 6
- 210000000653 nervous system Anatomy 0.000 description 6
- 150000007523 nucleic acids Chemical group 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 238000000540 analysis of variance Methods 0.000 description 5
- 125000004122 cyclic group Chemical class 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 108020004707 nucleic acids Proteins 0.000 description 5
- 102000039446 nucleic acids Human genes 0.000 description 5
- 239000000816 peptidomimetic Substances 0.000 description 5
- 210000000578 peripheral nerve Anatomy 0.000 description 5
- 230000002062 proliferating effect Effects 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 238000002965 ELISA Methods 0.000 description 4
- 208000003098 Ganglion Cysts Diseases 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 208000005400 Synovial Cyst Diseases 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 230000001588 bifunctional effect Effects 0.000 description 4
- 230000030833 cell death Effects 0.000 description 4
- 238000001516 cell proliferation assay Methods 0.000 description 4
- 238000004132 cross linking Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 230000014511 neuron projection development Effects 0.000 description 4
- 210000002027 skeletal muscle Anatomy 0.000 description 4
- 235000002639 sodium chloride Nutrition 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- 102000015336 Nerve Growth Factor Human genes 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 150000001718 carbodiimides Chemical class 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 238000009510 drug design Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 3
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 230000003278 mimic effect Effects 0.000 description 3
- 230000003387 muscular Effects 0.000 description 3
- 230000032405 negative regulation of neuron apoptotic process Effects 0.000 description 3
- 229940053128 nerve growth factor Drugs 0.000 description 3
- 230000016273 neuron death Effects 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 230000001228 trophic effect Effects 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 2
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 2
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 2
- 108010038152 CAT development factor Proteins 0.000 description 2
- 108010058699 Choline O-acetyltransferase Proteins 0.000 description 2
- 102100023460 Choline O-acetyltransferase Human genes 0.000 description 2
- 239000004971 Cross linker Substances 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical compound CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 208000025966 Neurological disease Diseases 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 201000000582 Retinoblastoma Diseases 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- NYTOUQBROMCLBJ-UHFFFAOYSA-N Tetranitromethane Chemical compound [O-][N+](=O)C([N+]([O-])=O)([N+]([O-])=O)[N+]([O-])=O NYTOUQBROMCLBJ-UHFFFAOYSA-N 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000003510 anti-fibrotic effect Effects 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 238000003782 apoptosis assay Methods 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 2
- 238000003149 assay kit Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000001886 ciliary effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 230000009260 cross reactivity Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- DVGHHMFBFOTGLM-UHFFFAOYSA-L fluorogold Chemical compound F[Au][Au]F DVGHHMFBFOTGLM-UHFFFAOYSA-L 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 210000000020 growth cone Anatomy 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 208000026278 immune system disease Diseases 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- 210000005230 lumbar spinal cord Anatomy 0.000 description 2
- 230000007659 motor function Effects 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 210000003666 myelinated nerve fiber Anatomy 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 230000006576 neuronal survival Effects 0.000 description 2
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 2
- 231100000028 nontoxic concentration Toxicity 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- OJUGVDODNPJEEC-UHFFFAOYSA-N phenylglyoxal Chemical compound O=CC(=O)C1=CC=CC=C1 OJUGVDODNPJEEC-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000005522 programmed cell death Effects 0.000 description 2
- 239000000700 radioactive tracer Substances 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 230000037152 sensory function Effects 0.000 description 2
- 238000010532 solid phase synthesis reaction Methods 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 210000001364 upper extremity Anatomy 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- FXYPGCIGRDZWNR-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-[[3-(2,5-dioxopyrrolidin-1-yl)oxy-3-oxopropyl]disulfanyl]propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSCCC(=O)ON1C(=O)CCC1=O FXYPGCIGRDZWNR-UHFFFAOYSA-N 0.000 description 1
- BEJKOYIMCGMNRB-GRHHLOCNSA-N (2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-amino-3-phenylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 BEJKOYIMCGMNRB-GRHHLOCNSA-N 0.000 description 1
- 125000003287 1H-imidazol-4-ylmethyl group Chemical group [H]N1C([H])=NC(C([H])([H])[*])=C1[H] 0.000 description 1
- ZHAORBUAOPBIBP-UHFFFAOYSA-N 2,2-dibromo-1-phenylethanone Chemical compound BrC(Br)C(=O)C1=CC=CC=C1 ZHAORBUAOPBIBP-UHFFFAOYSA-N 0.000 description 1
- 150000003923 2,5-pyrrolediones Chemical class 0.000 description 1
- JQPFYXFVUKHERX-UHFFFAOYSA-N 2-hydroxy-2-cyclohexen-1-one Natural products OC1=CCCCC1=O JQPFYXFVUKHERX-UHFFFAOYSA-N 0.000 description 1
- BIGBDMFRWJRLGJ-UHFFFAOYSA-N 3-benzyl-1,5-didiazoniopenta-1,4-diene-2,4-diolate Chemical compound [N-]=[N+]=CC(=O)C(C(=O)C=[N+]=[N-])CC1=CC=CC=C1 BIGBDMFRWJRLGJ-UHFFFAOYSA-N 0.000 description 1
- LQILVUYCDHSGEU-UHFFFAOYSA-N 4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexane-1-carboxylic acid Chemical compound C1CC(C(=O)O)CCC1CN1C(=O)C=CC1=O LQILVUYCDHSGEU-UHFFFAOYSA-N 0.000 description 1
- YRNWIFYIFSBPAU-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(N(C)C)C=C1 YRNWIFYIFSBPAU-UHFFFAOYSA-N 0.000 description 1
- NLPWSMKACWGINL-UHFFFAOYSA-N 4-azido-2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(N=[N+]=[N-])C=C1O NLPWSMKACWGINL-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 1
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 102000001189 Cyclic Peptides Human genes 0.000 description 1
- 108010069514 Cyclic Peptides Proteins 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- 101000663390 Drosophila melanogaster Protein spaetzle 5 Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 208000025818 Hereditary motor neurone disease Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000002260 Keloid Diseases 0.000 description 1
- 206010023330 Keloid scar Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 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
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 208000023178 Musculoskeletal disease Diseases 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102000052708 Recessive Genes Human genes 0.000 description 1
- 108700005079 Recessive Genes Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 208000002847 Surgical Wound Diseases 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 101710120037 Toxin CcdB Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 208000024248 Vascular System injury Diseases 0.000 description 1
- 208000012339 Vascular injury Diseases 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 150000008043 acidic salts Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000002226 anterior horn cell Anatomy 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000002737 cell proliferation kit Methods 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical compound NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 229940106681 chloroacetic acid Drugs 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 230000009693 chronic damage Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 239000008294 cold cream Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000005094 computer simulation Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- OILAIQUEIWYQPH-UHFFFAOYSA-N cyclohexane-1,2-dione Chemical compound O=C1CCCCC1=O OILAIQUEIWYQPH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- FFYPMLJYZAEMQB-UHFFFAOYSA-N diethyl pyrocarbonate Chemical compound CCOC(=O)OC(=O)OCC FFYPMLJYZAEMQB-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 125000004119 disulfanediyl group Chemical group *SS* 0.000 description 1
- 150000004662 dithiols Chemical group 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 210000002310 elbow joint Anatomy 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 210000003194 forelimb Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000030534 hereditary motor neuron disease Diseases 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 210000004754 hybrid cell Anatomy 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 239000008311 hydrophilic ointment Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000010324 immunological assay Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000030214 innervation Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 210000001117 keloid Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 238000012792 lyophilization process Methods 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
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 238000003032 molecular docking Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 210000003757 neuroblast Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000019581 neuron apoptotic process Effects 0.000 description 1
- 230000016195 neuron homeostasis Effects 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000008196 pharmacological composition Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000013105 post hoc analysis Methods 0.000 description 1
- 230000036515 potency Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000018883 protein targeting Effects 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 230000036573 scar formation Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 210000000323 shoulder joint Anatomy 0.000 description 1
- IHQKEDIOMGYHEB-UHFFFAOYSA-M sodium dimethylarsinate Chemical compound [Na+].C[As](C)([O-])=O IHQKEDIOMGYHEB-UHFFFAOYSA-M 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 208000002320 spinal muscular atrophy Diseases 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- RINCXYDBBGOEEQ-UHFFFAOYSA-N succinic anhydride Chemical class O=C1CCC(=O)O1 RINCXYDBBGOEEQ-UHFFFAOYSA-N 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 230000002477 vacuolizing effect Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 210000003857 wrist joint Anatomy 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
-
- 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
- A61P21/00—Drugs for disorders of the muscular or neuromuscular 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
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
-
- 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
- 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)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Toxicology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Pain & Pain Management (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Dermatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US44177203P | 2003-01-21 | 2003-01-21 | |
| PCT/US2004/001468 WO2004065410A2 (en) | 2003-01-21 | 2004-01-21 | Mntf peptides and compositions and methods of use |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010215438A Division JP4913895B2 (ja) | 2003-01-21 | 2010-09-27 | Ｍｎｔｆペプチドおよび組成物ならびに使用の方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2006516287A true JP2006516287A (ja) | 2006-06-29 |
Family
ID=32771972
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006501057A Withdrawn JP2006516287A (ja) | 2003-01-21 | 2004-01-21 | Ｍｎｔｆペプチドおよび組成物ならびに使用の方法 |
| JP2010215438A Expired - Fee Related JP4913895B2 (ja) | 2003-01-21 | 2010-09-27 | Ｍｎｔｆペプチドおよび組成物ならびに使用の方法 |
| JP2011226655A Pending JP2012046538A (ja) | 2003-01-21 | 2011-10-14 | Ｍｎｔｆペプチドおよび組成物ならびに使用の方法 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010215438A Expired - Fee Related JP4913895B2 (ja) | 2003-01-21 | 2010-09-27 | Ｍｎｔｆペプチドおよび組成物ならびに使用の方法 |
| JP2011226655A Pending JP2012046538A (ja) | 2003-01-21 | 2011-10-14 | Ｍｎｔｆペプチドおよび組成物ならびに使用の方法 |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US7183373B2 (enExample) |
| EP (1) | EP1587526B1 (enExample) |
| JP (3) | JP2006516287A (enExample) |
| AT (1) | ATE530191T1 (enExample) |
| AU (1) | AU2004205659B2 (enExample) |
| CA (1) | CA2506855C (enExample) |
| DK (1) | DK1587526T3 (enExample) |
| ES (1) | ES2375797T3 (enExample) |
| WO (1) | WO2004065410A2 (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010509345A (ja) * | 2006-11-10 | 2010-03-25 | ジェナボン バイオファーマシューティカルズ エルエルシー | Ｍｎｔｆペプチドおよびその類似体を用いて神経細胞障害を治療する方法 |
| JP2011513240A (ja) * | 2008-02-21 | 2011-04-28 | ダーマケア・ニューロサイエンス・インスティテュート | Ｍｎｔｆペプチドの美容および皮膚科用製剤 |
| WO2022244757A1 (ja) | 2021-05-18 | 2022-11-24 | 株式会社Ｌｔｔバイオファーマ | 抗癌剤の投与に伴う障害を治療又は予防するための医薬組成物 |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6841531B2 (en) | 1996-09-27 | 2005-01-11 | Genervon Biopharmaceuticals Llc | Methods and use of motoneuronotrophic factors |
| WO2004065410A2 (en) * | 2003-01-21 | 2004-08-05 | Genervon Biopharmaceuticals Llc | Mntf peptides and compositions and methods of use |
| AU2006315668B2 (en) * | 2005-11-10 | 2013-06-20 | Genervon Biopharmaceuticals Llc | MNTF differentiation and growth of stem cells |
| US8340193B2 (en) * | 2006-08-04 | 2012-12-25 | Microsoft Corporation | Wyner-Ziv and wavelet video coding |
| EP2000134A1 (en) * | 2007-06-06 | 2008-12-10 | Neuraxo Biopharmaceuticals GmbH | Use of a substance for the improvement of pns lesions |
| US20090233295A1 (en) * | 2008-01-29 | 2009-09-17 | Elias Georges | Trim59 directed diagnostics for neoplastic disease |
| US8846615B2 (en) * | 2008-02-21 | 2014-09-30 | Genervon Biopharmaceuticals, LLC | MNTF peptides |
| WO2016210123A1 (en) | 2015-06-26 | 2016-12-29 | Genervon Biopharmaceuticals, LLC | Methods of using gm604 in modulating als disease biomarkers leading to prognosis and therapeutic treatment for als disease |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001523942A (ja) * | 1996-09-27 | 2001-11-27 | ケイエム バイオテック，インコーポレイテッド | 運動ニューロン栄養性因子の単離および使用 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6841531B2 (en) * | 1996-09-27 | 2005-01-11 | Genervon Biopharmaceuticals Llc | Methods and use of motoneuronotrophic factors |
| WO2004065410A2 (en) * | 2003-01-21 | 2004-08-05 | Genervon Biopharmaceuticals Llc | Mntf peptides and compositions and methods of use |
-
2004
- 2004-01-21 WO PCT/US2004/001468 patent/WO2004065410A2/en not_active Ceased
- 2004-01-21 ES ES04704005T patent/ES2375797T3/es not_active Expired - Lifetime
- 2004-01-21 EP EP04704005A patent/EP1587526B1/en not_active Expired - Lifetime
- 2004-01-21 AT AT04704005T patent/ATE530191T1/de active
- 2004-01-21 US US10/541,343 patent/US7183373B2/en not_active Expired - Lifetime
- 2004-01-21 CA CA2506855A patent/CA2506855C/en not_active Expired - Lifetime
- 2004-01-21 AU AU2004205659A patent/AU2004205659B2/en not_active Ceased
- 2004-01-21 JP JP2006501057A patent/JP2006516287A/ja not_active Withdrawn
- 2004-01-21 DK DK04704005.0T patent/DK1587526T3/da active
-
2007
- 2007-01-25 US US11/657,815 patent/US7795215B2/en not_active Expired - Lifetime
-
2010
- 2010-09-27 JP JP2010215438A patent/JP4913895B2/ja not_active Expired - Fee Related
-
2011
- 2011-10-14 JP JP2011226655A patent/JP2012046538A/ja active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001523942A (ja) * | 1996-09-27 | 2001-11-27 | ケイエム バイオテック，インコーポレイテッド | 運動ニューロン栄養性因子の単離および使用 |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010509345A (ja) * | 2006-11-10 | 2010-03-25 | ジェナボン バイオファーマシューティカルズ エルエルシー | Ｍｎｔｆペプチドおよびその類似体を用いて神経細胞障害を治療する方法 |
| JP2011513240A (ja) * | 2008-02-21 | 2011-04-28 | ダーマケア・ニューロサイエンス・インスティテュート | Ｍｎｔｆペプチドの美容および皮膚科用製剤 |
| JP2014177464A (ja) * | 2008-02-21 | 2014-09-25 | Dermacare Neuroscience Institute | Ｍｎｔｆペプチドの美容および皮膚科用製剤 |
| WO2022244757A1 (ja) | 2021-05-18 | 2022-11-24 | 株式会社Ｌｔｔバイオファーマ | 抗癌剤の投与に伴う障害を治療又は予防するための医薬組成物 |
| KR20240008844A (ko) | 2021-05-18 | 2024-01-19 | 가부시키가이샤 엘티티 바이오파마 | 항암제의 투여에 수반되는 장애를 치료 또는 예방하기 위한 의약 조성물 |
Also Published As
| Publication number | Publication date |
|---|---|
| US7183373B2 (en) | 2007-02-27 |
| US20080125373A1 (en) | 2008-05-29 |
| US7795215B2 (en) | 2010-09-14 |
| ES2375797T3 (es) | 2012-03-06 |
| CA2506855C (en) | 2013-08-27 |
| WO2004065410A2 (en) | 2004-08-05 |
| JP2012046538A (ja) | 2012-03-08 |
| AU2004205659B2 (en) | 2009-03-26 |
| JP4913895B2 (ja) | 2012-04-11 |
| WO2004065410A3 (en) | 2004-12-16 |
| ATE530191T1 (de) | 2011-11-15 |
| DK1587526T3 (da) | 2012-02-06 |
| EP1587526B1 (en) | 2011-10-26 |
| EP1587526A2 (en) | 2005-10-26 |
| CA2506855A1 (en) | 2004-08-05 |
| JP2011042659A (ja) | 2011-03-03 |
| EP1587526A4 (en) | 2008-01-02 |
| AU2004205659A1 (en) | 2004-08-05 |
| US20060052299A1 (en) | 2006-03-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4913895B2 (ja) | Ｍｎｔｆペプチドおよび組成物ならびに使用の方法 | |
| EP0890105B1 (en) | Methods related to Alzheimer's disease for diagnosis, manufacture of medicaments and screening of substances and beta-amyloid related peptides | |
| CA2320490A1 (en) | Neuroprotective peptides and uses thereof | |
| US20150072936A1 (en) | Methods for promoting wound healing and/or reducing scar formation | |
| ES2250509T3 (es) | Analogos ciclicos solubles del peptido beta amiloide. | |
| JP2024113090A (ja) | 神経可塑性を誘導するための方法および組成物 | |
| US20200188451A1 (en) | OXALOBACTER FORMIGENES (Of)-DERIVED FACTORS FOR THE TREATMENT OF TREATMENT/PREVENTION OF EXCESS OXALATE LEVELS | |
| CN101696234B (zh) | 抗类风湿性关节炎的多肽及其在制药中的应用 | |
| EA013565B1 (ru) | Варианты полипептидов нейбластина, способы их получения и их применение | |
| JP4095673B2 (ja) | 運動ニューロン栄養性因子の単離および使用 | |
| JP5718649B2 (ja) | Ｍｎｔｆペプチド組成物およびその使用法 | |
| CZ219093A3 (en) | Insulin-like growth hormone binding protein derived from human bone | |
| AU754982B2 (en) | Compositions for promoting nerve regeneration | |
| WO1993009798A1 (en) | Therapeutic and diagnostic methods based on tissue specific nt-3 expression and receptor binding | |
| CA2191321A1 (en) | Gene coding for modified bone morphogenic protein receptor | |
| JP4168623B2 (ja) | オリゴペプチド | |
| HK1151242B (en) | Mntf peptide compositions and methods of use | |
| CA2221391A1 (en) | Neuron and neural tumour growth regulatory system, antibodies thereto and uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20070117 |
|
| RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20070327 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20070411 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20091201 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100226 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20100525 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100927 |
|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20101116 |