AU2006315668B2 - MNTF differentiation and growth of stem cells - Google Patents
MNTF differentiation and growth of stem cells Download PDFInfo
- Publication number
- AU2006315668B2 AU2006315668B2 AU2006315668A AU2006315668A AU2006315668B2 AU 2006315668 B2 AU2006315668 B2 AU 2006315668B2 AU 2006315668 A AU2006315668 A AU 2006315668A AU 2006315668 A AU2006315668 A AU 2006315668A AU 2006315668 B2 AU2006315668 B2 AU 2006315668B2
- Authority
- AU
- Australia
- Prior art keywords
- cells
- mntf
- peptide
- cell
- protein
- 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.)
- Ceased
Links
- 230000004069 differentiation Effects 0.000 title claims abstract description 65
- 210000000130 stem cell Anatomy 0.000 title abstract description 59
- 230000012010 growth Effects 0.000 title description 19
- 210000004027 cell Anatomy 0.000 claims abstract description 264
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 203
- 238000000034 method Methods 0.000 claims abstract description 115
- 210000002161 motor neuron Anatomy 0.000 claims abstract description 109
- 239000000203 mixture Substances 0.000 claims abstract description 42
- 230000004083 survival effect Effects 0.000 claims abstract description 31
- 210000001671 embryonic stem cell Anatomy 0.000 claims abstract description 25
- 108090000623 proteins and genes Proteins 0.000 claims description 71
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 claims description 66
- 229930002330 retinoic acid Natural products 0.000 claims description 63
- 229960001727 tretinoin Drugs 0.000 claims description 63
- 102000004169 proteins and genes Human genes 0.000 claims description 60
- 230000000694 effects Effects 0.000 claims description 49
- 230000014509 gene expression Effects 0.000 claims description 49
- 210000002569 neuron Anatomy 0.000 claims description 39
- 230000037361 pathway Effects 0.000 claims description 38
- 108010001127 Insulin Receptor Proteins 0.000 claims description 37
- 102000003746 Insulin Receptor Human genes 0.000 claims description 37
- 101100203200 Danio rerio shha gene Proteins 0.000 claims description 36
- 101150088976 shh gene Proteins 0.000 claims description 36
- -1 -HB9 Proteins 0.000 claims description 32
- 102000003693 Hedgehog Proteins Human genes 0.000 claims description 27
- 108090000031 Hedgehog Proteins Proteins 0.000 claims description 27
- 238000000338 in vitro Methods 0.000 claims description 24
- 108091000080 Phosphotransferase Proteins 0.000 claims description 23
- 102000020233 phosphotransferase Human genes 0.000 claims description 23
- 230000019491 signal transduction Effects 0.000 claims description 22
- 108091008611 Protein Kinase B Proteins 0.000 claims description 19
- 210000001178 neural stem cell Anatomy 0.000 claims description 18
- 210000002242 embryoid body Anatomy 0.000 claims description 17
- 102000001267 GSK3 Human genes 0.000 claims description 15
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 15
- 230000001419 dependent effect Effects 0.000 claims description 15
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims description 13
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims description 13
- 238000012423 maintenance Methods 0.000 claims description 11
- 102000011727 Caspases Human genes 0.000 claims description 10
- 108010076667 Caspases Proteins 0.000 claims description 10
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 claims description 10
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 claims description 9
- 102100025087 Insulin receptor substrate 1 Human genes 0.000 claims description 8
- 101710201824 Insulin receptor substrate 1 Proteins 0.000 claims description 8
- 108091007960 PI3Ks Proteins 0.000 claims description 8
- 239000003102 growth factor Substances 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 7
- 238000012258 culturing Methods 0.000 claims description 7
- 108010031794 IGF Type 1 Receptor Proteins 0.000 claims description 6
- 102000038455 IGF Type 1 Receptor Human genes 0.000 claims description 6
- 102000038460 IGF Type 2 Receptor Human genes 0.000 claims description 5
- 108010031792 IGF Type 2 Receptor Proteins 0.000 claims description 5
- 102000001253 Protein Kinase Human genes 0.000 claims description 5
- 108700025694 p53 Genes Proteins 0.000 claims description 5
- 108060006633 protein kinase Proteins 0.000 claims description 5
- 102000053171 Glial Fibrillary Acidic Human genes 0.000 claims description 4
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 claims description 4
- 108010069196 Neural Cell Adhesion Molecules Proteins 0.000 claims description 4
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 claims description 4
- 102100033019 Tyrosine-protein phosphatase non-receptor type 11 Human genes 0.000 claims description 4
- 101710116241 Tyrosine-protein phosphatase non-receptor type 11 Proteins 0.000 claims description 4
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 claims description 4
- 102100033067 Growth factor receptor-bound protein 2 Human genes 0.000 claims description 3
- 101000871017 Homo sapiens Growth factor receptor-bound protein 2 Proteins 0.000 claims description 3
- 101000997832 Homo sapiens Tyrosine-protein kinase JAK2 Proteins 0.000 claims description 3
- 102100025092 Insulin receptor substrate 2 Human genes 0.000 claims description 3
- 101710201820 Insulin receptor substrate 2 Proteins 0.000 claims description 3
- 102100031419 Insulin receptor substrate 4 Human genes 0.000 claims description 3
- 101710201816 Insulin receptor substrate 4 Proteins 0.000 claims description 3
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 3
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 3
- 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 claims description 3
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 claims description 2
- 101001092197 Homo sapiens RNA binding protein fox-1 homolog 3 Proteins 0.000 claims description 2
- 102000008730 Nestin Human genes 0.000 claims description 2
- 108010088225 Nestin Proteins 0.000 claims description 2
- 102000038030 PI3Ks Human genes 0.000 claims description 2
- 102100035530 RNA binding protein fox-1 homolog 3 Human genes 0.000 claims description 2
- LEBBDRXHHNYZIA-LDUWYPJVSA-N [(2s,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] n-[(z)-1,3-dihydroxyoctadec-4-en-2-yl]carbamate Chemical compound CCCCCCCCCCCCC\C=C/C(O)C(CO)NC(=O)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O LEBBDRXHHNYZIA-LDUWYPJVSA-N 0.000 claims description 2
- 210000005055 nestin Anatomy 0.000 claims description 2
- 210000005044 neurofilament Anatomy 0.000 claims description 2
- 230000004936 stimulating effect Effects 0.000 claims description 2
- 102000009664 Microtubule-Associated Proteins Human genes 0.000 claims 2
- 108010020004 Microtubule-Associated Proteins Proteins 0.000 claims 2
- 239000002771 cell marker Substances 0.000 claims 2
- 102100027453 Bcl2-associated agonist of cell death Human genes 0.000 claims 1
- 101710081085 Bcl2-associated agonist of cell death Proteins 0.000 claims 1
- 101150050712 CRK gene Proteins 0.000 claims 1
- 101100503636 Danio rerio fyna gene Proteins 0.000 claims 1
- 101100028478 Danio rerio pals1a gene Proteins 0.000 claims 1
- 101150018272 FYN gene Proteins 0.000 claims 1
- 101100150676 Mus musculus Styk1 gene Proteins 0.000 claims 1
- 101150096752 NCAM1 gene Proteins 0.000 claims 1
- 210000003061 neural cell Anatomy 0.000 abstract description 30
- 230000001225 therapeutic effect Effects 0.000 abstract description 19
- 238000004113 cell culture Methods 0.000 abstract description 18
- 230000001939 inductive effect Effects 0.000 abstract description 6
- 230000002708 enhancing effect Effects 0.000 abstract description 4
- 230000007774 longterm Effects 0.000 abstract description 2
- 235000001014 amino acid Nutrition 0.000 description 83
- 229940024606 amino acid Drugs 0.000 description 82
- 150000001413 amino acids Chemical class 0.000 description 73
- 102000004196 processed proteins & peptides Human genes 0.000 description 68
- 150000001875 compounds Chemical class 0.000 description 58
- 235000018102 proteins Nutrition 0.000 description 54
- 238000011282 treatment Methods 0.000 description 35
- 230000001537 neural effect Effects 0.000 description 34
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 29
- 210000001519 tissue Anatomy 0.000 description 29
- 229920001184 polypeptide Polymers 0.000 description 26
- 102000005962 receptors Human genes 0.000 description 26
- 108020003175 receptors Proteins 0.000 description 25
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 23
- 125000003275 alpha amino acid group Chemical group 0.000 description 22
- 208000035475 disorder Diseases 0.000 description 22
- 239000000463 material Substances 0.000 description 22
- 125000000539 amino acid group Chemical group 0.000 description 20
- 230000004044 response Effects 0.000 description 20
- 238000003556 assay Methods 0.000 description 19
- 230000004913 activation Effects 0.000 description 18
- 102000040430 polynucleotide Human genes 0.000 description 18
- 108091033319 polynucleotide Proteins 0.000 description 18
- 239000002157 polynucleotide Substances 0.000 description 18
- 235000002639 sodium chloride Nutrition 0.000 description 18
- 241000699666 Mus <mouse, genus> Species 0.000 description 17
- 239000003814 drug Substances 0.000 description 17
- 150000007523 nucleic acids Chemical class 0.000 description 16
- 230000026731 phosphorylation Effects 0.000 description 16
- 238000006366 phosphorylation reaction Methods 0.000 description 16
- 238000001727 in vivo Methods 0.000 description 15
- 239000002609 medium Substances 0.000 description 15
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 14
- 108010033276 Peptide Fragments Proteins 0.000 description 14
- 102000007079 Peptide Fragments Human genes 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 230000027455 binding Effects 0.000 description 14
- 239000003937 drug carrier Substances 0.000 description 14
- 238000009396 hybridization Methods 0.000 description 14
- 239000003550 marker Substances 0.000 description 14
- 102000039446 nucleic acids Human genes 0.000 description 14
- 108020004707 nucleic acids Proteins 0.000 description 14
- 210000000056 organ Anatomy 0.000 description 14
- 239000012634 fragment Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 102000016914 ras Proteins Human genes 0.000 description 13
- 108010014186 ras Proteins Proteins 0.000 description 13
- 239000000758 substrate Substances 0.000 description 13
- 239000000556 agonist Substances 0.000 description 12
- 239000011324 bead Substances 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- 102000037865 fusion proteins Human genes 0.000 description 12
- 108020001507 fusion proteins Proteins 0.000 description 12
- 239000003112 inhibitor Substances 0.000 description 12
- 229940125396 insulin Drugs 0.000 description 12
- 102000004877 Insulin Human genes 0.000 description 11
- 108090001061 Insulin Proteins 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- 239000003085 diluting agent Substances 0.000 description 11
- 239000005090 green fluorescent protein Substances 0.000 description 11
- WDHRPWOAMDJICD-FOAQWNCLSA-N n-[2-[(3'r,3'as,6's,6as,6bs,7'ar,9r,11as,11br)-3',6',10,11b-tetramethyl-3-oxospiro[1,2,4,6,6a,6b,7,8,11,11a-decahydrobenzo[a]fluorene-9,2'-3,3a,5,6,7,7a-hexahydrofuro[3,2-b]pyridine]-4'-yl]ethyl]-6-(3-phenylpropanoylamino)hexanamide Chemical compound C([C@@H](C)C[C@@H]1[C@@H]2[C@H]([C@]3(C(=C4C[C@@H]5[C@@]6(C)CCC(=O)CC6=CC[C@H]5[C@@H]4CC3)C)O1)C)N2CCNC(=O)CCCCCNC(=O)CCC1=CC=CC=C1 WDHRPWOAMDJICD-FOAQWNCLSA-N 0.000 description 11
- 150000003839 salts Chemical class 0.000 description 11
- 239000000523 sample Substances 0.000 description 11
- 230000011664 signaling Effects 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 10
- 210000002950 fibroblast Anatomy 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 230000006870 function Effects 0.000 description 10
- 239000008194 pharmaceutical composition Substances 0.000 description 10
- 239000002243 precursor Substances 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 101000576323 Homo sapiens Motor neuron and pancreas homeobox protein 1 Proteins 0.000 description 9
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 9
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 9
- 230000006907 apoptotic process Effects 0.000 description 9
- 210000002459 blastocyst Anatomy 0.000 description 9
- 210000003169 central nervous system Anatomy 0.000 description 9
- 239000012528 membrane Substances 0.000 description 9
- 210000004379 membrane Anatomy 0.000 description 9
- 239000000816 peptidomimetic Substances 0.000 description 9
- 230000035755 proliferation Effects 0.000 description 9
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 9
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 8
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 8
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 8
- 239000013543 active substance Substances 0.000 description 8
- 210000003050 axon Anatomy 0.000 description 8
- 239000001963 growth medium Substances 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
- 210000005155 neural progenitor cell Anatomy 0.000 description 8
- 230000001737 promoting effect Effects 0.000 description 8
- 230000001105 regulatory effect Effects 0.000 description 8
- 238000012552 review Methods 0.000 description 8
- 210000000278 spinal cord Anatomy 0.000 description 8
- 229940126585 therapeutic drug Drugs 0.000 description 8
- 239000013598 vector Substances 0.000 description 8
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 7
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 7
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 7
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 7
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 7
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 7
- 239000004472 Lysine Substances 0.000 description 7
- 101001055320 Myxine glutinosa Insulin-like growth factor Proteins 0.000 description 7
- 241000288906 Primates Species 0.000 description 7
- AMJJLDJPDLKNJA-UHFFFAOYSA-N [hydroxy(naphthalen-2-yl)methyl]phosphonic acid Chemical compound C1=CC=CC2=CC(C(O)P(O)(O)=O)=CC=C21 AMJJLDJPDLKNJA-UHFFFAOYSA-N 0.000 description 7
- 230000035578 autophosphorylation Effects 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 230000000295 complement effect Effects 0.000 description 7
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 239000003623 enhancer Substances 0.000 description 7
- 235000018977 lysine Nutrition 0.000 description 7
- 230000035515 penetration Effects 0.000 description 7
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 7
- 238000001262 western blot Methods 0.000 description 7
- 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 6
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 6
- SXGMVGOVILIERA-UHFFFAOYSA-N 2,3-diaminobutanoic acid Chemical compound CC(N)C(N)C(O)=O SXGMVGOVILIERA-UHFFFAOYSA-N 0.000 description 6
- XUJNEKJLAYXESH-UHFFFAOYSA-N Cysteine Chemical compound SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 6
- CKLJMWTZIZZHCS-UWTATZPHSA-N D-aspartic acid Chemical compound OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- 108060006662 GSK3 Proteins 0.000 description 6
- 102000034615 Glial cell line-derived neurotrophic factor Human genes 0.000 description 6
- 108091010837 Glial cell line-derived neurotrophic factor Proteins 0.000 description 6
- 244000060234 Gmelina philippensis Species 0.000 description 6
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 6
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 6
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 6
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 6
- 241001529936 Murinae Species 0.000 description 6
- 108090000742 Neurotrophin 3 Proteins 0.000 description 6
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 6
- 102000004584 Somatomedin Receptors Human genes 0.000 description 6
- 108010017622 Somatomedin Receptors Proteins 0.000 description 6
- 102100032889 Sortilin Human genes 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 6
- 230000009471 action Effects 0.000 description 6
- 238000013459 approach Methods 0.000 description 6
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 230000000903 blocking effect Effects 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 238000011161 development Methods 0.000 description 6
- 230000018109 developmental process Effects 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 239000012636 effector Substances 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 230000004927 fusion Effects 0.000 description 6
- 239000002502 liposome Substances 0.000 description 6
- 239000006166 lysate Substances 0.000 description 6
- 239000011159 matrix material Substances 0.000 description 6
- 210000003205 muscle Anatomy 0.000 description 6
- NFVJNJQRWPQVOA-UHFFFAOYSA-N n-[2-chloro-5-(trifluoromethyl)phenyl]-2-[3-(4-ethyl-5-ethylsulfanyl-1,2,4-triazol-3-yl)piperidin-1-yl]acetamide Chemical compound CCN1C(SCC)=NN=C1C1CN(CC(=O)NC=2C(=CC=C(C=2)C(F)(F)F)Cl)CCC1 NFVJNJQRWPQVOA-UHFFFAOYSA-N 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- 229960003104 ornithine Drugs 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 239000004475 Arginine Substances 0.000 description 5
- 102000029816 Collagenase Human genes 0.000 description 5
- 108060005980 Collagenase Proteins 0.000 description 5
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 5
- 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 5
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 5
- 102000009433 Insulin Receptor Substrate Proteins Human genes 0.000 description 5
- 108010034219 Insulin Receptor Substrate Proteins Proteins 0.000 description 5
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 description 5
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- ZSZXYWFCIKKZBT-ZVDPZPSOSA-N [(2r)-3-[[(2s,3s,5r,6s)-2,6-dihydroxy-3,4,5-triphosphonooxycyclohexyl]oxy-hydroxyphosphoryl]oxy-2-hexadecanoyloxypropyl] hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCC)COP(O)(=O)OC1[C@H](O)[C@H](OP(O)(O)=O)C(OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H]1O ZSZXYWFCIKKZBT-ZVDPZPSOSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 235000009697 arginine Nutrition 0.000 description 5
- 229960003121 arginine Drugs 0.000 description 5
- 108700000707 bcl-2-Associated X Proteins 0.000 description 5
- 102000055102 bcl-2-Associated X Human genes 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- CJGYSWNGNKCJSB-YVLZZHOMSA-N bucladesine Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](OC(=O)CCC)[C@@H]2N1C(N=CN=C2NC(=O)CCC)=C2N=C1 CJGYSWNGNKCJSB-YVLZZHOMSA-N 0.000 description 5
- 229960005263 bucladesine Drugs 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 229960002424 collagenase Drugs 0.000 description 5
- 235000018417 cysteine Nutrition 0.000 description 5
- 229960002433 cysteine Drugs 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 210000002257 embryonic structure Anatomy 0.000 description 5
- 230000001605 fetal effect Effects 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 229960002989 glutamic acid Drugs 0.000 description 5
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 5
- 235000004554 glutamine Nutrition 0.000 description 5
- 229960002885 histidine Drugs 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 238000010369 molecular cloning Methods 0.000 description 5
- 208000015122 neurodegenerative disease Diseases 0.000 description 5
- 210000004498 neuroglial cell Anatomy 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 239000001509 sodium citrate Substances 0.000 description 5
- 239000004094 surface-active agent Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 4
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 4
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 4
- 102000009465 Growth Factor Receptors Human genes 0.000 description 4
- 108010009202 Growth Factor Receptors Proteins 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 4
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 4
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 4
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 4
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 4
- 102000001708 Protein Isoforms Human genes 0.000 description 4
- 108010029485 Protein Isoforms Proteins 0.000 description 4
- 102000014400 SH2 domains Human genes 0.000 description 4
- 108050003452 SH2 domains Proteins 0.000 description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
- 108090000631 Trypsin Proteins 0.000 description 4
- 102000004142 Trypsin Human genes 0.000 description 4
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 4
- 108010016200 Zinc Finger Protein GLI1 Proteins 0.000 description 4
- 235000004279 alanine Nutrition 0.000 description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 229960005261 aspartic acid Drugs 0.000 description 4
- 239000003833 bile salt Substances 0.000 description 4
- 210000004899 c-terminal region Anatomy 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 230000009918 complex formation Effects 0.000 description 4
- 210000004351 coronary vessel Anatomy 0.000 description 4
- 238000004132 cross linking Methods 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 4
- 229940071106 ethylenediaminetetraacetate Drugs 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000000194 fatty acid Substances 0.000 description 4
- 229930195729 fatty acid Natural products 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 210000004602 germ cell Anatomy 0.000 description 4
- 235000013922 glutamic acid Nutrition 0.000 description 4
- 239000004220 glutamic acid Substances 0.000 description 4
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
- 235000014304 histidine Nutrition 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 4
- 102000028416 insulin-like growth factor binding Human genes 0.000 description 4
- 108091022911 insulin-like growth factor binding Proteins 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 108020004999 messenger RNA Proteins 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 210000001428 peripheral nervous system Anatomy 0.000 description 4
- 210000001778 pluripotent stem cell Anatomy 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 230000035935 pregnancy Effects 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 230000000069 prophylactic effect Effects 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 4
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000010532 solid phase synthesis reaction Methods 0.000 description 4
- 239000013589 supplement Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 239000002562 thickening agent Substances 0.000 description 4
- 230000002103 transcriptional effect Effects 0.000 description 4
- 239000012588 trypsin Substances 0.000 description 4
- LAQPKDLYOBZWBT-NYLDSJSYSA-N (2s,4s,5r,6r)-5-acetamido-2-{[(2s,3r,4s,5s,6r)-2-{[(2r,3r,4r,5r)-5-acetamido-1,2-dihydroxy-6-oxo-4-{[(2s,3s,4r,5s,6s)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy}hexan-3-yl]oxy}-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy}-4-hydroxy-6-[(1r,2r)-1,2,3-trihydrox Chemical compound O[C@H]1[C@H](O)[C@H](O)[C@H](C)O[C@H]1O[C@H]([C@@H](NC(C)=O)C=O)[C@@H]([C@H](O)CO)O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@H](O)CO)C(O)=O)[C@@H](O)[C@@H](CO)O1 LAQPKDLYOBZWBT-NYLDSJSYSA-N 0.000 description 3
- FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 3
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 3
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 3
- 108010058699 Choline O-acetyltransferase Proteins 0.000 description 3
- 102100023460 Choline O-acetyltransferase Human genes 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 3
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 3
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 3
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- QEFRNWWLZKMPFJ-ZXPFJRLXSA-N L-methionine (R)-S-oxide Chemical compound C[S@@](=O)CC[C@H]([NH3+])C([O-])=O QEFRNWWLZKMPFJ-ZXPFJRLXSA-N 0.000 description 3
- QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Natural products CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 102100032352 Leukemia inhibitory factor Human genes 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- VEYYWZRYIYDQJM-ZETCQYMHSA-N N(2)-acetyl-L-lysine Chemical compound CC(=O)N[C@H](C([O-])=O)CCCC[NH3+] VEYYWZRYIYDQJM-ZETCQYMHSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 102100022397 Nitric oxide synthase, brain Human genes 0.000 description 3
- 102100028452 Nitric oxide synthase, endothelial Human genes 0.000 description 3
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 3
- 108091034117 Oligonucleotide Proteins 0.000 description 3
- 108010077895 Sarcosine Proteins 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- 102000013380 Smoothened Receptor Human genes 0.000 description 3
- 108010090739 Smoothened Receptor Proteins 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- 108010088665 Zinc Finger Protein Gli2 Proteins 0.000 description 3
- 230000004075 alteration Effects 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 235000009582 asparagine Nutrition 0.000 description 3
- 229960001230 asparagine Drugs 0.000 description 3
- 235000003704 aspartic acid Nutrition 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 3
- 230000001588 bifunctional effect Effects 0.000 description 3
- 229940093761 bile salts Drugs 0.000 description 3
- 229960002685 biotin Drugs 0.000 description 3
- 235000020958 biotin Nutrition 0.000 description 3
- 239000011616 biotin Substances 0.000 description 3
- 150000001718 carbodiimides Chemical class 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 239000006143 cell culture medium Substances 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 239000002738 chelating agent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000000749 co-immunoprecipitation Methods 0.000 description 3
- 230000001143 conditioned effect Effects 0.000 description 3
- 230000021615 conjugation Effects 0.000 description 3
- 230000001186 cumulative effect Effects 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 108010007093 dispase Proteins 0.000 description 3
- 238000009510 drug design Methods 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 210000002744 extracellular matrix Anatomy 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- 210000003754 fetus Anatomy 0.000 description 3
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 3
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 3
- 210000004392 genitalia Anatomy 0.000 description 3
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 238000003018 immunoassay Methods 0.000 description 3
- 238000003365 immunocytochemistry Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000004005 microsphere Substances 0.000 description 3
- 230000000877 morphologic effect Effects 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 230000004770 neurodegeneration Effects 0.000 description 3
- 230000014511 neuron projection development Effects 0.000 description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
- 238000010647 peptide synthesis reaction Methods 0.000 description 3
- 210000000578 peripheral nerve Anatomy 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 3
- 238000007747 plating Methods 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 230000000644 propagated effect Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 235000004400 serine Nutrition 0.000 description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 3
- 229940038773 trisodium citrate Drugs 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- BVAUMRCGVHUWOZ-ZETCQYMHSA-N (2s)-2-(cyclohexylazaniumyl)propanoate Chemical compound OC(=O)[C@H](C)NC1CCCCC1 BVAUMRCGVHUWOZ-ZETCQYMHSA-N 0.000 description 2
- MRTPISKDZDHEQI-YFKPBYRVSA-N (2s)-2-(tert-butylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC(C)(C)C MRTPISKDZDHEQI-YFKPBYRVSA-N 0.000 description 2
- NPDBDJFLKKQMCM-SCSAIBSYSA-N (2s)-2-amino-3,3-dimethylbutanoic acid Chemical compound CC(C)(C)[C@H](N)C(O)=O NPDBDJFLKKQMCM-SCSAIBSYSA-N 0.000 description 2
- DNDVHMGBCGSRIY-LURJTMIESA-N (2s)-2-amino-3-(1,3-benzothiazol-2-yl)propanoic acid Chemical compound C1=CC=C2SC(C[C@H](N)C(O)=O)=NC2=C1 DNDVHMGBCGSRIY-LURJTMIESA-N 0.000 description 2
- BWKMGYQJPOAASG-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid Chemical compound C1=CC=C2CNC(C(=O)O)CC2=C1 BWKMGYQJPOAASG-UHFFFAOYSA-N 0.000 description 2
- RZRNAYUHWVFMIP-KTKRTIGZSA-N 1-oleoylglycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-KTKRTIGZSA-N 0.000 description 2
- NYCRCTMDYITATC-UHFFFAOYSA-N 2-fluorophenylalanine Chemical compound OC(=O)C(N)CC1=CC=CC=C1F NYCRCTMDYITATC-UHFFFAOYSA-N 0.000 description 2
- XWHHYOYVRVGJJY-QMMMGPOBSA-N 4-fluoro-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(F)C=C1 XWHHYOYVRVGJJY-QMMMGPOBSA-N 0.000 description 2
- YCRAFFCYWOUEOF-DLOVCJGASA-N Ala-Phe-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=CC=C1 YCRAFFCYWOUEOF-DLOVCJGASA-N 0.000 description 2
- 101100297694 Arabidopsis thaliana PIP2-7 gene Proteins 0.000 description 2
- NVPHRWNWTKYIST-BPNCWPANSA-N Arg-Tyr-Ala Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C)C(O)=O)CC1=CC=C(O)C=C1 NVPHRWNWTKYIST-BPNCWPANSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 102000003952 Caspase 3 Human genes 0.000 description 2
- 108090000397 Caspase 3 Proteins 0.000 description 2
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 239000004971 Cross linker Substances 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102100038026 DNA fragmentation factor subunit alpha Human genes 0.000 description 2
- SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 2
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical compound CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 2
- 101100015729 Drosophila melanogaster drk gene Proteins 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- NIGWMJHCCYYCSF-UHFFFAOYSA-N Fenclonine Chemical compound OC(=O)C(N)CC1=CC=C(Cl)C=C1 NIGWMJHCCYYCSF-UHFFFAOYSA-N 0.000 description 2
- 102100037362 Fibronectin Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- 102000038624 GSKs Human genes 0.000 description 2
- 108091007911 GSKs Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- 102000005720 Glutathione transferase Human genes 0.000 description 2
- 108010070675 Glutathione transferase Proteins 0.000 description 2
- 108010001483 Glycogen Synthase Proteins 0.000 description 2
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 2
- 108010003272 Hyaluronate lyase Proteins 0.000 description 2
- 102000001974 Hyaluronidases Human genes 0.000 description 2
- LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 description 2
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 2
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 2
- QUOGESRFPZDMMT-UHFFFAOYSA-N L-Homoarginine Natural products OC(=O)C(N)CCCCNC(N)=N QUOGESRFPZDMMT-UHFFFAOYSA-N 0.000 description 2
- 125000000998 L-alanino group Chemical group [H]N([*])[C@](C([H])([H])[H])([H])C(=O)O[H] 0.000 description 2
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 2
- QUOGESRFPZDMMT-YFKPBYRVSA-N L-homoarginine Chemical compound OC(=O)[C@@H](N)CCCCNC(N)=N QUOGESRFPZDMMT-YFKPBYRVSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 108010085895 Laminin Proteins 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- DBXMFHGGHMXYHY-DCAQKATOSA-N Met-Leu-Ser Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O DBXMFHGGHMXYHY-DCAQKATOSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical class ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 2
- AKCRVYNORCOYQT-YFKPBYRVSA-N N-methyl-L-valine Chemical compound CN[C@@H](C(C)C)C(O)=O AKCRVYNORCOYQT-YFKPBYRVSA-N 0.000 description 2
- KSPIYJQBLVDRRI-UHFFFAOYSA-N N-methylisoleucine Chemical compound CCC(C)C(NC)C(O)=O KSPIYJQBLVDRRI-UHFFFAOYSA-N 0.000 description 2
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- 102000007072 Nerve Growth Factors Human genes 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 101710111444 Nitric oxide synthase, brain Proteins 0.000 description 2
- 101710090055 Nitric oxide synthase, endothelial Proteins 0.000 description 2
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 102000000017 Patched Receptors Human genes 0.000 description 2
- 108010069873 Patched Receptors Proteins 0.000 description 2
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 201000000582 Retinoblastoma Diseases 0.000 description 2
- 101100456541 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) MEC3 gene Proteins 0.000 description 2
- 101100483663 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) UFD1 gene Proteins 0.000 description 2
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 239000006180 TBST buffer Substances 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
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 108091000117 Tyrosine 3-Monooxygenase Proteins 0.000 description 2
- 102000048218 Tyrosine 3-monooxygenases Human genes 0.000 description 2
- 235000010724 Wisteria floribunda Nutrition 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229940035674 anesthetics Drugs 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 2
- 210000001130 astrocyte Anatomy 0.000 description 2
- CREXVNNSNOKDHW-UHFFFAOYSA-N azaniumylideneazanide Chemical group N[N] CREXVNNSNOKDHW-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- 210000000941 bile Anatomy 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 125000002091 cationic group Chemical class 0.000 description 2
- 210000005056 cell body Anatomy 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 229960002173 citrulline Drugs 0.000 description 2
- 235000013477 citrulline Nutrition 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 238000001246 colloidal dispersion Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000003436 cytoskeletal effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 2
- 210000001787 dendrite Anatomy 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 238000007667 floating Methods 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- 239000003193 general anesthetic agent Substances 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 229940049906 glutamate Drugs 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 description 2
- 229960003180 glutathione Drugs 0.000 description 2
- 101150098203 grb2 gene Proteins 0.000 description 2
- 102000034345 heterotrimeric G proteins Human genes 0.000 description 2
- 108091006093 heterotrimeric G proteins Proteins 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 108010035817 human DNA fragmentation factor Proteins 0.000 description 2
- 210000003917 human chromosome Anatomy 0.000 description 2
- 229960002773 hyaluronidase Drugs 0.000 description 2
- 238000003119 immunoblot Methods 0.000 description 2
- 238000001114 immunoprecipitation Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000003999 initiator Substances 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- VWHRYODZTDMVSS-QMMMGPOBSA-N m-fluoro-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC(F)=C1 VWHRYODZTDMVSS-QMMMGPOBSA-N 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 108010082117 matrigel Proteins 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 239000000693 micelle Substances 0.000 description 2
- 239000003094 microcapsule Substances 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 238000003032 molecular docking Methods 0.000 description 2
- 230000007659 motor function Effects 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 239000002088 nanocapsule Substances 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 239000003900 neurotrophic factor Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 210000004248 oligodendroglia Anatomy 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- OJUGVDODNPJEEC-UHFFFAOYSA-N phenylglyoxal Chemical compound O=CC(=O)C1=CC=CC=C1 OJUGVDODNPJEEC-UHFFFAOYSA-N 0.000 description 2
- DCWXELXMIBXGTH-QMMMGPOBSA-N phosphonotyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-QMMMGPOBSA-N 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000007832 reinnervation Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 229910001415 sodium ion Inorganic materials 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 208000020431 spinal cord injury Diseases 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 229940032147 starch Drugs 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000008093 supporting effect Effects 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- 230000001960 triggered effect Effects 0.000 description 2
- 230000001228 trophic effect Effects 0.000 description 2
- 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 2
- 239000004474 valine Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- 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
- YMXHPSHLTSZXKH-RVBZMBCESA-N (2,5-dioxopyrrolidin-1-yl) 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoate Chemical compound C([C@H]1[C@H]2NC(=O)N[C@H]2CS1)CCCC(=O)ON1C(=O)CCC1=O YMXHPSHLTSZXKH-RVBZMBCESA-N 0.000 description 1
- OQQOAWVKVDAJOI-UHFFFAOYSA-N (2-dodecanoyloxy-3-hydroxypropyl) dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCCCCCC OQQOAWVKVDAJOI-UHFFFAOYSA-N 0.000 description 1
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 1
- OPCHFPHZPIURNA-MFERNQICSA-N (2s)-2,5-bis(3-aminopropylamino)-n-[2-(dioctadecylamino)acetyl]pentanamide Chemical compound CCCCCCCCCCCCCCCCCCN(CC(=O)NC(=O)[C@H](CCCNCCCN)NCCCN)CCCCCCCCCCCCCCCCCC OPCHFPHZPIURNA-MFERNQICSA-N 0.000 description 1
- IYKLZBIWFXPUCS-VIFPVBQESA-N (2s)-2-(naphthalen-1-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=CC=CC2=C1 IYKLZBIWFXPUCS-VIFPVBQESA-N 0.000 description 1
- RWLSBXBFZHDHHX-VIFPVBQESA-N (2s)-2-(naphthalen-2-ylamino)propanoic acid Chemical compound C1=CC=CC2=CC(N[C@@H](C)C(O)=O)=CC=C21 RWLSBXBFZHDHHX-VIFPVBQESA-N 0.000 description 1
- HOZBSSWDEKVXNO-BXRBKJIMSA-N (2s)-2-azanylbutanedioic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O.OC(=O)[C@@H](N)CC(O)=O HOZBSSWDEKVXNO-BXRBKJIMSA-N 0.000 description 1
- LJRDOKAZOAKLDU-UDXJMMFXSA-N (2s,3s,4r,5r,6r)-5-amino-2-(aminomethyl)-6-[(2r,3s,4r,5s)-5-[(1r,2r,3s,5r,6s)-3,5-diamino-2-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric ac Chemical compound OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO LJRDOKAZOAKLDU-UDXJMMFXSA-N 0.000 description 1
- 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
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- CMCBDXRRFKYBDG-UHFFFAOYSA-N 1-dodecoxydodecane Chemical compound CCCCCCCCCCCCOCCCCCCCCCCCC CMCBDXRRFKYBDG-UHFFFAOYSA-N 0.000 description 1
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- 108700020469 14-3-3 Proteins 0.000 description 1
- 102000004899 14-3-3 Proteins Human genes 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
- OGNSCSPNOLGXSM-UHFFFAOYSA-N 2,4-diaminobutyric acid Chemical compound NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- 150000003923 2,5-pyrrolediones Chemical class 0.000 description 1
- FKJSFKCZZIXQIP-UHFFFAOYSA-N 2-bromo-1-(4-bromophenyl)ethanone Chemical compound BrCC(=O)C1=CC=C(Br)C=C1 FKJSFKCZZIXQIP-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 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
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-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
- BXRLWGXPSRYJDZ-UHFFFAOYSA-N 3-cyanoalanine Chemical compound OC(=O)C(N)CC#N BXRLWGXPSRYJDZ-UHFFFAOYSA-N 0.000 description 1
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-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
- CMUHFUGDYMFHEI-QMMMGPOBSA-N 4-amino-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N)C=C1 CMUHFUGDYMFHEI-QMMMGPOBSA-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
- IZZIWIAOVZOBLF-UHFFFAOYSA-N 5-methoxysalicylic acid Chemical compound COC1=CC=C(O)C(C(O)=O)=C1 IZZIWIAOVZOBLF-UHFFFAOYSA-N 0.000 description 1
- 108010013238 70-kDa Ribosomal Protein S6 Kinases Proteins 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-M 9-cis,12-cis-Octadecadienoate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC([O-])=O OYHQOLUKZRVURQ-HZJYTTRNSA-M 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 230000007730 Akt signaling Effects 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- 102000004580 Aspartic Acid Proteases Human genes 0.000 description 1
- 108010017640 Aspartic Acid Proteases Proteins 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 102000051485 Bcl-2 family Human genes 0.000 description 1
- 108700038897 Bcl-2 family Proteins 0.000 description 1
- 101100297249 Borrelia burgdorferi (strain ATCC 35210 / B31 / CIP 102532 / DSM 4680) pfp gene Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 1
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 1
- 101100533230 Caenorhabditis elegans ser-2 gene Proteins 0.000 description 1
- 101100315624 Caenorhabditis elegans tyr-1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 241001432959 Chernes 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
- 108010069514 Cyclic Peptides Proteins 0.000 description 1
- 102000001189 Cyclic Peptides Human genes 0.000 description 1
- QASFUMOKHFSJGL-LAFRSMQTSA-N Cyclopamine Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H](CC2=C3C)[C@@H]1[C@@H]2CC[C@@]13O[C@@H]2C[C@H](C)CN[C@H]2[C@H]1C QASFUMOKHFSJGL-LAFRSMQTSA-N 0.000 description 1
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-SCSAIBSYSA-N D-arginine Chemical compound OC(=O)[C@H](N)CCCNC(N)=N ODKSFYDXXFIFQN-SCSAIBSYSA-N 0.000 description 1
- 229930028154 D-arginine Natural products 0.000 description 1
- WHUUTDBJXJRKMK-GSVOUGTGSA-N D-glutamic acid Chemical compound OC(=O)[C@H](N)CCC(O)=O WHUUTDBJXJRKMK-GSVOUGTGSA-N 0.000 description 1
- 229930182847 D-glutamic acid Natural products 0.000 description 1
- HNDVDQJCIGZPNO-RXMQYKEDSA-N D-histidine Chemical compound OC(=O)[C@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-RXMQYKEDSA-N 0.000 description 1
- 229930195721 D-histidine Natural products 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- 101710182628 DNA fragmentation factor subunit alpha Proteins 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- VYZAHLCBVHPDDF-UHFFFAOYSA-N Dinitrochlorobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 VYZAHLCBVHPDDF-UHFFFAOYSA-N 0.000 description 1
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 102000007989 Effector Caspases Human genes 0.000 description 1
- 108010089510 Effector Caspases Proteins 0.000 description 1
- 201000009051 Embryonal Carcinoma Diseases 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
- 108010062466 Enzyme Precursors Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000013446 GTP Phosphohydrolases Human genes 0.000 description 1
- 102100029974 GTPase HRas Human genes 0.000 description 1
- 102100030708 GTPase KRas Human genes 0.000 description 1
- 101710113436 GTPase KRas Proteins 0.000 description 1
- 102100039788 GTPase NRas Human genes 0.000 description 1
- 108091006109 GTPases Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 102000004878 Gelsolin Human genes 0.000 description 1
- 108090001064 Gelsolin Proteins 0.000 description 1
- 102100039955 Gem-associated protein 6 Human genes 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 102000058061 Glucose Transporter Type 4 Human genes 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- VAXIVIPMCTYSHI-YUMQZZPRSA-N Gly-His-Asp Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)CN VAXIVIPMCTYSHI-YUMQZZPRSA-N 0.000 description 1
- GLACUWHUYFBSPJ-FJXKBIBVSA-N Gly-Pro-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN GLACUWHUYFBSPJ-FJXKBIBVSA-N 0.000 description 1
- 206010053759 Growth retardation Diseases 0.000 description 1
- 101000684275 Homo sapiens ADP-ribosylation factor 3 Proteins 0.000 description 1
- 101001052035 Homo sapiens Fibroblast growth factor 2 Proteins 0.000 description 1
- 101000584633 Homo sapiens GTPase HRas Proteins 0.000 description 1
- 101000744505 Homo sapiens GTPase NRas Proteins 0.000 description 1
- 101000886614 Homo sapiens Gem-associated protein 6 Proteins 0.000 description 1
- 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 description 1
- 101001128158 Homo sapiens Nanos homolog 2 Proteins 0.000 description 1
- 101001128156 Homo sapiens Nanos homolog 3 Proteins 0.000 description 1
- 101001124309 Homo sapiens Nitric oxide synthase, endothelial Proteins 0.000 description 1
- 101001124991 Homo sapiens Nitric oxide synthase, inducible Proteins 0.000 description 1
- 101001120056 Homo sapiens Phosphatidylinositol 3-kinase regulatory subunit alpha Proteins 0.000 description 1
- 101001130437 Homo sapiens Ras-related protein Rap-2b Proteins 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- 101000987310 Homo sapiens Serine/threonine-protein kinase PAK 2 Proteins 0.000 description 1
- 101001117143 Homo sapiens [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- 102100024392 Insulin gene enhancer protein ISL-1 Human genes 0.000 description 1
- 102100024390 Insulin gene enhancer protein ISL-2 Human genes 0.000 description 1
- 101710156777 Insulin gene enhancer protein ISL-2 Proteins 0.000 description 1
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- 125000000393 L-methionino group Chemical group [H]OC(=O)[C@@]([H])(N([H])[*])C([H])([H])C(SC([H])([H])[H])([H])[H] 0.000 description 1
- DGYHPLMPMRKMPD-UHFFFAOYSA-N L-propargyl glycine Natural products OC(=O)C(N)CC#C DGYHPLMPMRKMPD-UHFFFAOYSA-N 0.000 description 1
- 125000000510 L-tryptophano group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[C@@]([H])(C(O[H])=O)N([H])[*])C2=C1[H] 0.000 description 1
- 229920002884 Laureth 4 Polymers 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- CQQGCWPXDHTTNF-GUBZILKMSA-N Leu-Ala-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(O)=O CQQGCWPXDHTTNF-GUBZILKMSA-N 0.000 description 1
- 102000004058 Leukemia inhibitory factor Human genes 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 102000008763 Neurofilament Proteins Human genes 0.000 description 1
- 108010088373 Neurofilament Proteins Proteins 0.000 description 1
- 108010008858 Nitric Oxide Synthase Type I Proteins 0.000 description 1
- 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 description 1
- 102000011779 Nitric Oxide Synthase Type II Human genes 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- BZQFBWGGLXLEPQ-UHFFFAOYSA-N O-phosphoryl-L-serine Natural products OC(=O)C(N)COP(O)(O)=O BZQFBWGGLXLEPQ-UHFFFAOYSA-N 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
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 102000004020 Oxygenases Human genes 0.000 description 1
- 108090000417 Oxygenases Proteins 0.000 description 1
- 101150075113 PFK2 gene Proteins 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010059712 Pronase Proteins 0.000 description 1
- 102100033479 RAF proto-oncogene serine/threonine-protein kinase Human genes 0.000 description 1
- 101710141955 RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 description 1
- 101150040459 RAS gene Proteins 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 102100023320 Ral guanine nucleotide dissociation stimulator Human genes 0.000 description 1
- 108050008437 Ral guanine nucleotide dissociation stimulator Proteins 0.000 description 1
- 102100031426 Ras GTPase-activating protein 1 Human genes 0.000 description 1
- 108050004017 Ras GTPase-activating protein 1 Proteins 0.000 description 1
- 102000003901 Ras GTPase-activating proteins Human genes 0.000 description 1
- 108090000231 Ras GTPase-activating proteins Proteins 0.000 description 1
- 102100031421 Ras-related protein Rap-2b Human genes 0.000 description 1
- 108091005682 Receptor kinases Proteins 0.000 description 1
- 108700005079 Recessive Genes Proteins 0.000 description 1
- 102000052708 Recessive Genes Human genes 0.000 description 1
- 108091006300 SLC2A4 Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- IDQFQFVEWMWRQQ-DLOVCJGASA-N Ser-Ala-Phe Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O IDQFQFVEWMWRQQ-DLOVCJGASA-N 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- 102100027939 Serine/threonine-protein kinase PAK 2 Human genes 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 1
- 102100021796 Sonic hedgehog protein Human genes 0.000 description 1
- 101100029402 Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145) pfkA2 gene Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- RQLNEFOBQAVGSY-WDSOQIARSA-N Trp-Met-Leu Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(O)=O RQLNEFOBQAVGSY-WDSOQIARSA-N 0.000 description 1
- 101710102803 Tumor suppressor ARF Proteins 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 102100024150 [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial Human genes 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000036982 action potential Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 1
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000004873 anchoring Methods 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000001139 anti-pruritic effect Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000003908 antipruritic agent Substances 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 230000005775 apoptotic pathway Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
- 108010047857 aspartylglycine Proteins 0.000 description 1
- 239000003212 astringent agent Substances 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 230000006287 biotinylation Effects 0.000 description 1
- 238000007413 biotinylation Methods 0.000 description 1
- 210000004703 blastocyst inner cell mass Anatomy 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 210000002302 brachial artery Anatomy 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 230000009460 calcium influx Effects 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- UHBYWPGGCSDKFX-UHFFFAOYSA-N carboxyglutamic acid Chemical compound OC(=O)C(N)CC(C(O)=O)C(O)=O UHBYWPGGCSDKFX-UHFFFAOYSA-N 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 101150055276 ced-3 gene Proteins 0.000 description 1
- 230000025084 cell cycle arrest Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 210000004671 cell-free system Anatomy 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 230000003727 cerebral blood flow Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 210000004720 cerebrum Anatomy 0.000 description 1
- 230000008859 change Effects 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
- 230000009816 chondrogenic differentiation Effects 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 239000003593 chromogenic compound Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 230000005757 colony formation Effects 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 229940125807 compound 37 Drugs 0.000 description 1
- 238000005094 computer simulation Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- OILAIQUEIWYQPH-UHFFFAOYSA-N cyclohexane-1,2-dione Chemical compound O=C1CCCCC1=O OILAIQUEIWYQPH-UHFFFAOYSA-N 0.000 description 1
- QASFUMOKHFSJGL-UHFFFAOYSA-N cyclopamine Natural products C1C=C2CC(O)CCC2(C)C(CC2=C3C)C1C2CCC13OC2CC(C)CNC2C1C QASFUMOKHFSJGL-UHFFFAOYSA-N 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000010217 densitometric analysis Methods 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 229950006137 dexfosfoserine Drugs 0.000 description 1
- 229960002086 dextran Drugs 0.000 description 1
- 229960000633 dextran sulfate Drugs 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 229960001193 diclofenac sodium Drugs 0.000 description 1
- FFYPMLJYZAEMQB-UHFFFAOYSA-N diethyl pyrocarbonate Chemical compound CCOC(=O)OC(=O)OCC FFYPMLJYZAEMQB-UHFFFAOYSA-N 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 150000004662 dithiols Chemical group 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 238000007878 drug screening assay Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 210000003981 ectoderm Anatomy 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 210000002308 embryonic cell Anatomy 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 210000001900 endoderm Anatomy 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 230000004720 fertilization Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000000684 flow cytometry Methods 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
- 239000012737 fresh medium Substances 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 210000001654 germ layer Anatomy 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- 108010087860 glutathione receptor Proteins 0.000 description 1
- UPWGQKDVAURUGE-UHFFFAOYSA-N glycerine monooleate Natural products CCCCCCCCC=CCCCCCCCC(=O)OC(CO)CO UPWGQKDVAURUGE-UHFFFAOYSA-N 0.000 description 1
- RZRNAYUHWVFMIP-HXUWFJFHSA-N glycerol monolinoleate Natural products CCCCCCCCC=CCCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-HXUWFJFHSA-N 0.000 description 1
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 230000002710 gonadal effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000000020 growth cone Anatomy 0.000 description 1
- 150000003278 haem Chemical class 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 238000012203 high throughput assay Methods 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
- QRMZSPFSDQBLIX-UHFFFAOYSA-N homovanillic acid Chemical compound COC1=CC(CC(O)=O)=CC=C1O QRMZSPFSDQBLIX-UHFFFAOYSA-N 0.000 description 1
- 102000008277 human DNA fragmentation factor Human genes 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 210000003090 iliac artery Anatomy 0.000 description 1
- 150000002463 imidates Chemical class 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical group O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 108010090448 insulin gene enhancer binding protein Isl-1 Proteins 0.000 description 1
- 210000004692 intercellular junction Anatomy 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000006831 intrinsic signaling Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 210000005053 lamin Anatomy 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 229940062711 laureth-9 Drugs 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 229940049918 linoleate Drugs 0.000 description 1
- 229960004488 linolenic acid Drugs 0.000 description 1
- KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000005230 lumbar spinal cord Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 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
- 239000012139 lysis buffer Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000007898 magnetic cell sorting Methods 0.000 description 1
- 238000009115 maintenance therapy Methods 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 241001515942 marmosets Species 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000002175 menstrual effect Effects 0.000 description 1
- 210000000713 mesentery Anatomy 0.000 description 1
- 210000003716 mesoderm Anatomy 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- YCXSYMVGMXQYNT-UHFFFAOYSA-N methyl 3-[(4-azidophenyl)disulfanyl]propanimidate Chemical compound COC(=N)CCSSC1=CC=C(N=[N+]=[N-])C=C1 YCXSYMVGMXQYNT-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 238000000329 molecular dynamics simulation Methods 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 description 1
- 229940074096 monoolein Drugs 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000003666 myelinated nerve fiber Anatomy 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 229940105132 myristate Drugs 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000002077 nanosphere Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 210000000933 neural crest Anatomy 0.000 description 1
- 210000003757 neuroblast Anatomy 0.000 description 1
- 230000001272 neurogenic effect Effects 0.000 description 1
- 210000000715 neuromuscular junction Anatomy 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- CQYBNXGHMBNGCG-RNJXMRFFSA-N octahydroindole-2-carboxylic acid Chemical compound C1CCC[C@H]2N[C@H](C(=O)O)C[C@@H]21 CQYBNXGHMBNGCG-RNJXMRFFSA-N 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 229960002446 octanoic acid Drugs 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 239000003605 opacifier Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-O oxonium Chemical compound [OH3+] XLYOFNOQVPJJNP-UHFFFAOYSA-O 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229960001639 penicillamine Drugs 0.000 description 1
- 102000023856 peptide binding proteins Human genes 0.000 description 1
- 108091008399 peptide binding proteins Proteins 0.000 description 1
- 102000014187 peptide receptors Human genes 0.000 description 1
- 108010011903 peptide receptors Proteins 0.000 description 1
- 230000037050 permeability transition Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 108010051242 phenylalanylserine Proteins 0.000 description 1
- 229960002895 phenylbutazone Drugs 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
- 150000003915 phosphatidylinositol 4,5-bisphosphates Chemical class 0.000 description 1
- 229940067631 phospholipid Drugs 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- BZQFBWGGLXLEPQ-REOHCLBHSA-N phosphoserine Chemical compound OC(=O)[C@@H](N)COP(O)(O)=O BZQFBWGGLXLEPQ-REOHCLBHSA-N 0.000 description 1
- USRGIUJOYOXOQJ-GBXIJSLDSA-N phosphothreonine Chemical compound OP(=O)(O)O[C@H](C)[C@H](N)C(O)=O USRGIUJOYOXOQJ-GBXIJSLDSA-N 0.000 description 1
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- ONJQDTZCDSESIW-UHFFFAOYSA-N polidocanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO ONJQDTZCDSESIW-UHFFFAOYSA-N 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 108010055896 polyornithine Proteins 0.000 description 1
- 229920002714 polyornithine Polymers 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000001902 propagating effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 210000004129 prosencephalon Anatomy 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 238000000163 radioactive labelling Methods 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 102000001378 ras Guanine Nucleotide Exchange Factors Human genes 0.000 description 1
- 108010080092 ras Guanine Nucleotide Exchange Factors Proteins 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000002629 repopulating effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000008886 response to retinoic acid Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- XMVJITFPVVRMHC-UHFFFAOYSA-N roxarsone Chemical group OC1=CC=C([As](O)(O)=O)C=C1[N+]([O-])=O XMVJITFPVVRMHC-UHFFFAOYSA-N 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 210000004116 schwann cell Anatomy 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 229940091258 selenium supplement Drugs 0.000 description 1
- 230000037152 sensory function 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
- 229940076279 serotonin Drugs 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 230000009645 skeletal growth Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- IHQKEDIOMGYHEB-UHFFFAOYSA-M sodium dimethylarsinate Chemical compound [Na+].C[As](C)([O-])=O IHQKEDIOMGYHEB-UHFFFAOYSA-M 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 229960004025 sodium salicylate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- DFVFTMTWCUHJBL-BQBZGAKWSA-N statine Chemical compound CC(C)C[C@H](N)[C@@H](O)CC(O)=O DFVFTMTWCUHJBL-BQBZGAKWSA-N 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004654 survival pathway Effects 0.000 description 1
- 230000007755 survival signaling Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 208000001608 teratocarcinoma Diseases 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000009772 tissue formation Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 210000004881 tumor cell Anatomy 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
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 230000002477 vacuolizing effect Effects 0.000 description 1
- 239000002550 vasoactive agent Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- QDLHCMPXEPAAMD-QAIWCSMKSA-N wortmannin Chemical compound C1([C@]2(C)C3=C(C4=O)OC=C3C(=O)O[C@@H]2COC)=C4[C@@H]2CCC(=O)[C@@]2(C)C[C@H]1OC(C)=O QDLHCMPXEPAAMD-QAIWCSMKSA-N 0.000 description 1
- QDLHCMPXEPAAMD-UHFFFAOYSA-N wortmannin Natural products COCC1OC(=O)C2=COC(C3=O)=C2C1(C)C1=C3C2CCC(=O)C2(C)CC1OC(C)=O QDLHCMPXEPAAMD-UHFFFAOYSA-N 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical class [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
- 210000004340 zona pellucida Anatomy 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Marine Sciences & Fisheries (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Hematology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Emergency Medicine (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
- Psychiatry (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US73570205P | 2005-11-10 | 2005-11-10 | |
| US60/735,702 | 2005-11-10 | ||
| US84176606P | 2006-09-01 | 2006-09-01 | |
| US60/841,766 | 2006-09-01 | ||
| US85802206P | 2006-11-10 | 2006-11-10 | |
| PCT/US2006/043874 WO2007058982A2 (en) | 2005-11-10 | 2006-11-10 | Mntf differentiation and growth of stem cells |
| US60/858,022 | 2006-11-10 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2006315668A1 AU2006315668A1 (en) | 2007-05-24 |
| AU2006315668B2 true AU2006315668B2 (en) | 2013-06-20 |
Family
ID=38049179
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2006315668A Ceased AU2006315668B2 (en) | 2005-11-10 | 2006-11-10 | MNTF differentiation and growth of stem cells |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US8986676B2 (enExample) |
| EP (1) | EP1965826B1 (enExample) |
| JP (2) | JP5270362B2 (enExample) |
| CN (1) | CN101374537B (enExample) |
| AU (1) | AU2006315668B2 (enExample) |
| CA (1) | CA2626728A1 (enExample) |
| WO (1) | WO2007058982A2 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2028268A1 (en) * | 2007-08-20 | 2009-02-25 | Université Libre De Bruxelles | Generation of neuronal cells from pluripotent stem cells |
| CN101951942B (zh) * | 2008-02-21 | 2014-09-03 | 健能万生物制药公司 | Mntf肽组合物及使用方法 |
| JPWO2010137722A1 (ja) * | 2009-05-26 | 2012-11-15 | 武田薬品工業株式会社 | 再生医薬のスクリーニング方法 |
| US9770471B2 (en) | 2011-08-17 | 2017-09-26 | President And Fellows Of Harvard College | Conversion of somatic cells into functional spinal motor neurons, and methods and uses thereof |
| CN110684734A (zh) * | 2011-11-04 | 2020-01-14 | 纪念斯隆-凯特琳癌症中心 | 用于植入的中脑多巴胺（da）神经元 |
| CN104073468B (zh) * | 2014-07-16 | 2016-04-27 | 栾佐 | 获得人源OPCs的方法和OPCs培养基 |
| CN106459912B (zh) | 2014-11-14 | 2021-05-25 | 再生医科学股份有限公司 | 软骨细胞的无血清培养方法、及无血清培养基 |
| 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 |
| CN110381981A (zh) * | 2016-12-23 | 2019-10-25 | 健能万生物制药公司 | 在诊断和治疗阿尔茨海默病中使用gm6的方法 |
| US12364985B2 (en) * | 2018-05-11 | 2025-07-22 | Georgia Tech Research Corporation | Systems and methods for electronic surface antigen expression analysis using magnetophoresis |
| CN118853569B (zh) * | 2024-09-29 | 2025-03-04 | 星奕昂(上海)生物科技有限公司 | 一种拟胚体消化液及其在分离造血干细胞中的应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003044175A2 (en) * | 2001-11-20 | 2003-05-30 | Genervon Biopharmaceuticals Llc | Methods and use of motoneuronotropic factors |
| WO2004065410A2 (en) * | 2003-01-21 | 2004-08-05 | Genervon Biopharmaceuticals Llc | Mntf peptides and compositions and methods of use |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5843780A (en) | 1995-01-20 | 1998-12-01 | Wisconsin Alumni Research Foundation | Primate embryonic stem cells |
| US6309877B1 (en) * | 1996-09-27 | 2001-10-30 | Km Biotech, Inc. | Polynucleotides encoding motoneuronotrophic factors |
| US6300117B1 (en) | 1997-09-15 | 2001-10-09 | Genencor International, Inc. | Proteases from gram-positive organisms |
| AU2001263199B2 (en) | 2000-05-17 | 2004-09-16 | Asterias Biotherapeutics, Inc. | Neural progenitor cell populations |
| US7390659B2 (en) * | 2002-07-16 | 2008-06-24 | The Trustees Of Columbia University In The City Of New York | Methods for inducing differentiation of embryonic stem cells and uses thereof |
| CA2544347A1 (en) * | 2003-11-07 | 2005-05-26 | Genervon Biopharmaceuticals Llc | Motoneuronotrophic factor gene sequences |
-
2006
- 2006-11-10 JP JP2008540231A patent/JP5270362B2/ja not_active Expired - Fee Related
- 2006-11-10 EP EP06837375.2A patent/EP1965826B1/en not_active Not-in-force
- 2006-11-10 AU AU2006315668A patent/AU2006315668B2/en not_active Ceased
- 2006-11-10 WO PCT/US2006/043874 patent/WO2007058982A2/en not_active Ceased
- 2006-11-10 CN CN200680041827.0A patent/CN101374537B/zh not_active Expired - Fee Related
- 2006-11-10 US US12/093,452 patent/US8986676B2/en not_active Expired - Fee Related
- 2006-11-10 CA CA002626728A patent/CA2626728A1/en not_active Abandoned
-
2013
- 2013-03-04 JP JP2013042001A patent/JP2013177388A/ja not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003044175A2 (en) * | 2001-11-20 | 2003-05-30 | Genervon Biopharmaceuticals Llc | Methods and use of motoneuronotropic factors |
| WO2004065410A2 (en) * | 2003-01-21 | 2004-08-05 | Genervon Biopharmaceuticals Llc | Mntf peptides and compositions and methods of use |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2013177388A (ja) | 2013-09-09 |
| EP1965826B1 (en) | 2014-12-31 |
| EP1965826A2 (en) | 2008-09-10 |
| CN101374537A (zh) | 2009-02-25 |
| HK1125824A1 (zh) | 2009-08-21 |
| US8986676B2 (en) | 2015-03-24 |
| WO2007058982A3 (en) | 2008-09-25 |
| CA2626728A1 (en) | 2007-05-24 |
| WO2007058982A2 (en) | 2007-05-24 |
| JP2009515891A (ja) | 2009-04-16 |
| AU2006315668A1 (en) | 2007-05-24 |
| US20090117085A1 (en) | 2009-05-07 |
| EP1965826A4 (en) | 2010-08-25 |
| CN101374537B (zh) | 2016-04-20 |
| JP5270362B2 (ja) | 2013-08-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2013177388A (ja) | 幹細胞のｍｎｔｆ分化および成長 | |
| JP2005534650A (ja) | エリスロポイエチンおよびインスリン様増殖因子の神経保護的相乗作用 | |
| AU2007317730B2 (en) | Methods of treating neuronal disorders using MNTF peptides and analogs thereof | |
| US20090227521A1 (en) | Use of compounds in the treatment of ischemia and neurodegeneration | |
| AU2008289209A1 (en) | Methods for promoting stem cell proliferation and survival | |
| CA2716392C (en) | Mntf peptide compositions and methods of use | |
| Li et al. | Human amniotic mesenchymal stem cell-conditioned medium inhibited LPS-induced cell injury and inflammation by modulating CD14/TLR4-mediated signaling pathway in monocytes | |
| HK1125824B (en) | Mntf differentiation and growth of stem cells | |
| Higashida et al. | Skin-derived precursors differentiating into dopaminergic neuronal cells in the brains of Parkinson disease model rats | |
| HK1137623B (en) | Methods of treating neuronal disorders using mntf peptides and analogs thereof | |
| HK1151242B (en) | Mntf peptide compositions and methods of use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |