JP2015513896A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2015513896A5 JP2015513896A5 JP2015500623A JP2015500623A JP2015513896A5 JP 2015513896 A5 JP2015513896 A5 JP 2015513896A5 JP 2015500623 A JP2015500623 A JP 2015500623A JP 2015500623 A JP2015500623 A JP 2015500623A JP 2015513896 A5 JP2015513896 A5 JP 2015513896A5
- Authority
- JP
- Japan
- Prior art keywords
- bromo
- paulon
- compound
- cell
- pauron
- 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.)
- Granted
Links
- 230000037361 pathway Effects 0.000 claims description 52
- 150000001875 compounds Chemical class 0.000 claims description 45
- 239000012190 activator Substances 0.000 claims description 33
- IVOMOUWHDPKRLL-KQYNXXCUSA-N cAMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 claims description 33
- 239000003112 inhibitor Substances 0.000 claims description 28
- 230000002401 inhibitory effect Effects 0.000 claims description 28
- 230000037041 intracellular level Effects 0.000 claims description 28
- 102000001267 GSK3 Human genes 0.000 claims description 26
- 108060006662 GSK3 Proteins 0.000 claims description 26
- 101710003421 FGF Proteins 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 22
- 210000004027 cells Anatomy 0.000 claims description 21
- 210000003205 Muscles Anatomy 0.000 claims description 20
- 238000007423 screening assay Methods 0.000 claims description 18
- -1 4-nitrophenylhydrazono Chemical group 0.000 claims description 16
- 210000000130 stem cell Anatomy 0.000 claims description 16
- 210000001057 Myoblasts, Smooth Muscle Anatomy 0.000 claims description 14
- 210000001109 Blastomeres Anatomy 0.000 claims description 13
- 210000002351 Embryonic Muscle Cell Anatomy 0.000 claims description 12
- OHCQJHSOBUTRHG-KGGHGJDLSA-N (3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxododecahydro-1H-benzo[f]chromen-5-yl acetate 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 claims description 10
- 239000003550 marker Substances 0.000 claims description 10
- 230000001965 increased Effects 0.000 claims description 9
- 102000019460 EC 4.6.1.1 Human genes 0.000 claims description 8
- 108060000200 EC 4.6.1.1 Proteins 0.000 claims description 8
- 206010028289 Muscle atrophy Diseases 0.000 claims description 8
- 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 claims description 8
- 201000000585 muscular atrophy Diseases 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- DDLZLOKCJHBUHD-WAVHTBQISA-N 6-bromoindirubin-3'-oxime Chemical compound O=C/1NC2=CC(Br)=CC=C2C\1=C\1/C(=N/O)/C2=CC=CC=C2N/1 DDLZLOKCJHBUHD-WAVHTBQISA-N 0.000 claims description 6
- OHCQJHSOBUTRHG-ZYIXGEAZSA-N Coleonol Natural products 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-ZYIXGEAZSA-N 0.000 claims description 6
- 102100008634 FGF2 Human genes 0.000 claims description 6
- 101700082364 FGF2 Proteins 0.000 claims description 6
- 210000002540 Macrophages Anatomy 0.000 claims description 6
- 239000006143 cell culture media Substances 0.000 claims description 6
- 230000001809 detectable Effects 0.000 claims description 6
- 229930002911 forskolin Natural products 0.000 claims description 6
- 210000003098 myoblast Anatomy 0.000 claims description 6
- 230000001114 myogenic Effects 0.000 claims description 6
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- FNTJNENAIGWCII-UHFFFAOYSA-N 7,8-dihydro-1-benzazepine-6-thione Chemical compound N1=CC=CC=C2C(=S)CCC=C21 FNTJNENAIGWCII-UHFFFAOYSA-N 0.000 claims description 4
- DQFQCHIDRBIESA-UHFFFAOYSA-N Benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 claims description 4
- 102000009016 Cholera Toxin Human genes 0.000 claims description 4
- 108010049048 Cholera Toxin Proteins 0.000 claims description 4
- 241000252212 Danio rerio Species 0.000 claims description 4
- 206010022114 Injury Diseases 0.000 claims description 4
- 102000004877 Insulin Human genes 0.000 claims description 4
- 108090001061 Insulin Proteins 0.000 claims description 4
- FLAQQSHRLBFIEZ-UHFFFAOYSA-N N-Methyl-N-nitroso-4-oxo-4-(3-pyridyl)butyl amine Chemical compound O=NN(C)CCCC(=O)C1=CC=CN=C1 FLAQQSHRLBFIEZ-UHFFFAOYSA-N 0.000 claims description 4
- 102100015313 VIP Human genes 0.000 claims description 4
- 101700003320 VIP Proteins 0.000 claims description 4
- 230000003213 activating Effects 0.000 claims description 4
- 239000000048 adrenergic agonist Substances 0.000 claims description 4
- 102000016966 beta-2 Adrenergic Receptors Human genes 0.000 claims description 4
- 108010014499 beta-2 Adrenergic Receptors Proteins 0.000 claims description 4
- 230000017531 blood circulation Effects 0.000 claims description 4
- 239000003710 calcium ionophore Substances 0.000 claims description 4
- 230000004069 differentiation Effects 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 201000009910 diseases by infectious agent Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 4
- 230000001939 inductive effect Effects 0.000 claims description 4
- 230000028161 membrane depolarization Effects 0.000 claims description 4
- 230000020763 muscle atrophy Effects 0.000 claims description 4
- 108020004707 nucleic acids Proteins 0.000 claims description 4
- 150000007523 nucleic acids Chemical class 0.000 claims description 4
- 239000002571 phosphodiesterase inhibitor Substances 0.000 claims description 4
- 230000001817 pituitary Effects 0.000 claims description 4
- 210000001778 pluripotent stem cell Anatomy 0.000 claims description 4
- 238000003530 single readout Methods 0.000 claims description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 4
- 102000034387 fluorescent proteins Human genes 0.000 claims description 3
- 108091006031 fluorescent proteins Proteins 0.000 claims description 3
- 230000000051 modifying Effects 0.000 claims description 3
- NVDRMQSURAQWNN-UHFFFAOYSA-N 1-[4-amino-2-(4-methoxyanilino)-1,3-thiazol-5-yl]ethanone Chemical compound C1=CC(OC)=CC=C1NC1=NC(N)=C(C(C)=O)S1 NVDRMQSURAQWNN-UHFFFAOYSA-N 0.000 claims description 2
- CKDGJQLBXUOVSI-UHFFFAOYSA-N 1-benzyl-3-(5-nitro-1,3-thiazol-2-yl)urea Chemical compound S1C([N+](=O)[O-])=CN=C1NC(=O)NCC1=CC=CC=C1 CKDGJQLBXUOVSI-UHFFFAOYSA-N 0.000 claims description 2
- VIZDGKDXNCKNQB-UHFFFAOYSA-N 1-butyl-3-(5-nitro-1,3-thiazol-2-yl)urea Chemical compound CCCCNC(=O)NC1=NC=C([N+]([O-])=O)S1 VIZDGKDXNCKNQB-UHFFFAOYSA-N 0.000 claims description 2
- WRGQSWVCFNIUNZ-GDCKJWNLSA-N 1-oleoyl-sn-glycerol 3-phosphate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)COP(O)(O)=O WRGQSWVCFNIUNZ-GDCKJWNLSA-N 0.000 claims description 2
- GEXADGHBWSFCIJ-UHFFFAOYSA-N 2-(3-methoxyphenyl)-N-(5-nitro-1,3-thiazol-2-yl)acetamide Chemical compound COC1=CC=CC(CC(=O)NC=2SC(=CN=2)[N+]([O-])=O)=C1 GEXADGHBWSFCIJ-UHFFFAOYSA-N 0.000 claims description 2
- XNSQGYWHCMJSML-UHFFFAOYSA-N 2-(3-methylphenyl)-N-(5-nitro-1,3-thiazol-2-yl)acetamide Chemical compound CC1=CC=CC(CC(=O)NC=2SC(=CN=2)[N+]([O-])=O)=C1 XNSQGYWHCMJSML-UHFFFAOYSA-N 0.000 claims description 2
- DQCBWYVIFLSTMV-UHFFFAOYSA-N 2-(4-fluorophenyl)-N-(5-nitro-1,3-thiazol-2-yl)propanamide Chemical compound C=1C=C(F)C=CC=1C(C)C(=O)NC1=NC=C([N+]([O-])=O)S1 DQCBWYVIFLSTMV-UHFFFAOYSA-N 0.000 claims description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- QOOKTOYWEDZCMO-UHFFFAOYSA-N 3-(4-methoxyphenyl)-N-(5-nitro-1,3-thiazol-2-yl)propanamide Chemical compound C1=CC(OC)=CC=C1CCC(=O)NC1=NC=C([N+]([O-])=O)S1 QOOKTOYWEDZCMO-UHFFFAOYSA-N 0.000 claims description 2
- IYNDTACKOAXKBJ-UHFFFAOYSA-N 3-[[4-[2-(3-chloroanilino)pyrimidin-4-yl]pyridin-2-yl]amino]propan-1-ol Chemical compound C1=NC(NCCCO)=CC(C=2N=C(NC=3C=C(Cl)C=CC=3)N=CC=2)=C1 IYNDTACKOAXKBJ-UHFFFAOYSA-N 0.000 claims description 2
- AGPPXTWBOAJADV-UHFFFAOYSA-N 4-(4-methoxyphenyl)-N-(5-nitro-1,3-thiazol-2-yl)butanamide Chemical compound C1=CC(OC)=CC=C1CCCC(=O)NC1=NC=C([N+]([O-])=O)S1 AGPPXTWBOAJADV-UHFFFAOYSA-N 0.000 claims description 2
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N 4-{1-hydroxy-2-[(propan-2-yl)amino]ethyl}benzene-1,2-diol Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 claims description 2
- MDZCSIDIPDZWKL-UHFFFAOYSA-N 6-N-[2-[[4-(2,4-dichlorophenyl)-5-imidazol-1-ylpyrimidin-2-yl]amino]ethyl]-3-nitropyridine-2,6-diamine Chemical compound C1=C([N+]([O-])=O)C(N)=NC(NCCNC=2N=C(C(=CN=2)N2C=NC=C2)C=2C(=CC(Cl)=CC=2)Cl)=C1 MDZCSIDIPDZWKL-UHFFFAOYSA-N 0.000 claims description 2
- 102100010854 ADM Human genes 0.000 claims description 2
- 108090000953 Adrenomedullin Proteins 0.000 claims description 2
- ULCUCJFASIJEOE-NPECTJMMSA-N Adrenomedullin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)NCC(=O)N[C@@H]1C(N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CSSC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)[C@@H](C)O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 ULCUCJFASIJEOE-NPECTJMMSA-N 0.000 claims description 2
- BIIVYFLTOXDAOV-YVEFUNNKSA-N Alvocidib Chemical compound O[C@@H]1CN(C)CC[C@@H]1C1=C(O)C=C(O)C2=C1OC(C=1C(=CC=CC=1)Cl)=CC2=O BIIVYFLTOXDAOV-YVEFUNNKSA-N 0.000 claims description 2
- 229960004484 CARBACHOL Drugs 0.000 claims description 2
- AQGNHMOJWBZFQQ-UHFFFAOYSA-N CT 99021 Chemical compound CC1=CNC(C=2C(=NC(NCCNC=3N=CC(=CC=3)C#N)=NC=2)C=2C(=CC(Cl)=CC=2)Cl)=N1 AQGNHMOJWBZFQQ-UHFFFAOYSA-N 0.000 claims description 2
- AIXAANGOTKPUOY-UHFFFAOYSA-N Carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 claims description 2
- 210000002242 Embryoid Bodies Anatomy 0.000 claims description 2
- YSFTYXKQUONNFY-NQXPEFQPSA-N FGF2 Chemical compound C([C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CO)NC(=O)CNC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H]1NCCC1)C1=CC=CC=C1 YSFTYXKQUONNFY-NQXPEFQPSA-N 0.000 claims description 2
- 108090000379 Fibroblast Growth Factor 2 Proteins 0.000 claims description 2
- 102000003974 Fibroblast Growth Factor 2 Human genes 0.000 claims description 2
- 108050007372 Fibroblast growth factor family Proteins 0.000 claims description 2
- 102000018233 Fibroblast growth factor family Human genes 0.000 claims description 2
- 102100010475 GATA2 Human genes 0.000 claims description 2
- 101700001555 GATA2 Proteins 0.000 claims description 2
- 102000019058 Glycogen Synthase Kinase 3 beta Human genes 0.000 claims description 2
- 108010051975 Glycogen Synthase Kinase 3 beta Proteins 0.000 claims description 2
- QPCBNXNDVYOBIP-WHFBIAKZSA-N Hymenialdisine Chemical compound NC1=NC(=O)C([C@@H]2[C@@H]3C=C(Br)N=C3C(=O)NCC2)=N1 QPCBNXNDVYOBIP-WHFBIAKZSA-N 0.000 claims description 2
- 229940039009 Isoproterenol Drugs 0.000 claims description 2
- 102100005905 MYF5 Human genes 0.000 claims description 2
- 101700000140 MYF5 Proteins 0.000 claims description 2
- 102100018549 MYOG Human genes 0.000 claims description 2
- 210000002027 Muscle, Skeletal Anatomy 0.000 claims description 2
- 108010035768 MyoD Protein Proteins 0.000 claims description 2
- 108010056785 Myogenin Proteins 0.000 claims description 2
- HAQCGFVINUGJBS-UHFFFAOYSA-N N-(5-nitro-1,3-thiazol-2-yl)pentanamide Chemical compound CCCCC(=O)NC1=NC=C([N+]([O-])=O)S1 HAQCGFVINUGJBS-UHFFFAOYSA-N 0.000 claims description 2
- SNICXCGAKADSCV-JTQLQIEISA-N Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 2
- 229960002715 Nicotine Drugs 0.000 claims description 2
- 101700011681 PAX3 Proteins 0.000 claims description 2
- 101700064753 PAX7 Proteins 0.000 claims description 2
- 108010003541 Platelet Activating Factor Proteins 0.000 claims description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N Saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 claims description 2
- 229940081974 Saccharin Drugs 0.000 claims description 2
- DUYSYHSSBDVJSM-KRWOKUGFSA-N Sphingosine-1-phosphate Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)COP(O)(O)=O DUYSYHSSBDVJSM-KRWOKUGFSA-N 0.000 claims description 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims description 2
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 2
- 108010086427 Transforming growth factor alpha Proteins 0.000 claims description 2
- 230000004913 activation Effects 0.000 claims description 2
- 238000004166 bioassay Methods 0.000 claims description 2
- 239000004202 carbamide Substances 0.000 claims description 2
- 229940082638 cardiac stimulant Phosphodiesterase inhibitors Drugs 0.000 claims description 2
- 239000002771 cell marker Substances 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- BOLFFYUDEVMACE-UHFFFAOYSA-N cyclohepta[b]indole Chemical compound C1=CC=CC=C2C3=CC=CC=C3N=C21 BOLFFYUDEVMACE-UHFFFAOYSA-N 0.000 claims description 2
- 230000018109 developmental process Effects 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 2
- 239000000284 extract Substances 0.000 claims description 2
- 102000037240 fusion proteins Human genes 0.000 claims description 2
- 108020001507 fusion proteins Proteins 0.000 claims description 2
- 150000004676 glycans Polymers 0.000 claims description 2
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims description 2
- 229960001317 isoprenaline Drugs 0.000 claims description 2
- 108010053292 macrophage stimulating protein Proteins 0.000 claims description 2
- 102000027675 major histocompatibility complex family Human genes 0.000 claims description 2
- 108091007937 major histocompatibility complex family Proteins 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 210000001704 mesoblast Anatomy 0.000 claims description 2
- 229930015196 nicotine Natural products 0.000 claims description 2
- 229920001542 oligosaccharide Polymers 0.000 claims description 2
- 150000002482 oligosaccharides Polymers 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 239000000816 peptidomimetic Substances 0.000 claims description 2
- 229920001282 polysaccharide Polymers 0.000 claims description 2
- 239000005017 polysaccharide Substances 0.000 claims description 2
- 150000004804 polysaccharides Polymers 0.000 claims description 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 2
- 230000035755 proliferation Effects 0.000 claims description 2
- 102000004169 proteins and genes Human genes 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 claims description 2
- 235000019204 saccharin Nutrition 0.000 claims description 2
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 claims description 2
- 230000004936 stimulating Effects 0.000 claims description 2
- 201000009032 substance abuse Diseases 0.000 claims description 2
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 claims 1
- UHDGCWIWMRVCDJ-XVFCMESISA-N Cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-XVFCMESISA-N 0.000 claims 1
- 150000003905 phosphatidylinositols Chemical group 0.000 claims 1
- 210000001671 Embryonic Stem Cells Anatomy 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000005305 organ development Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Description
1ã€ã®å±é¢ã«ãããŠãæ¬æ现æžã«ã¯ããŒãã©ãã£ãã·ã¥å²ç现èã«ãããŠååŠååç©ãŸãã¯çµæç©ãã¹ã¯ãªãŒãã³ã°ããããã®æ¹æ³ã§ãã£ãŠãè©Šéšååç©ã®ååšäžã§ãŒãã©ãã£ãã·ã¥å²ç现èã®éå£ãå¹é€ããå·¥çšã§ãã£ãŠãå²ç现èããèå
ã¿ã³ãã¯è³ªã«èåããã现èç³»èç¹ç°çããŒã«ãŒïŒCLSMïŒïŒããªãã¡ãCSLM::FPã³ã³ã¹ãã©ã¯ãïŒãå«ããå·¥çšãããã³FPãå¯èŠåããå·¥çšããå«ãæ¹æ³ããæäŸããããFPã®ã¬ãã«ãŸãã¯éã®å€åã¯ãè©Šéšååç©ãããã®çŽ°èç³»èç¹ç°çããŒã«ãŒãçºçŸããèåšã®çºçã調ç¯ããããšã瀺ããFPã®ã¬ãã«ãŸãã¯çºçŸã¯ãåç
§ãŸãã¯å¯Ÿç
§ã«å¯ŸããŠçžå¯Ÿçã«æ±ºå®ããåŸãã
[æ¬çºæ1001]
幹现èã®çå现èãžã®ååãèªå°ããæ¹æ³ã§ãã£ãŠãïŒiïŒGSK3çµè·¯é»å®³ç©è³ªïŒïŒiiïŒ3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žïŒcAMPïŒã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ïŒããã³ïŒiiiïŒFGFçµè·¯æŽ»æ§åç©è³ªãã®å°ãªããšã2ã€ãšå ±ã«å¹¹çŽ°èãå¹é€ããå·¥çšãå«ããæ¹æ³ã
[æ¬çºæ1002]
å¹é€ããå·¥çšããGSK3çµè·¯é»å®³ç©è³ªã3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ãããã³FGFçµè·¯æŽ»æ§åç©è³ªã®ååšäžã§è¡ããããæ¬çºæ1001ã®æ¹æ³ã
[æ¬çºæ1003]
幹现èãã人工å€èœæ§å¹¹ïŒiPSïŒçŽ°èãèæ§å¹¹ïŒESïŒçŽ°èãŸãã¯å€ååèœæ§å¹¹çŽ°èã§ãããæ¬çºæ1001ãŸãã¯1002ã®æ¹æ³ã
[æ¬çºæ1004]
GSK3çµè·¯é»å®³ç©è³ªããGSK3βé»å®³ç©è³ªã§ãããæ¬çºæ1001ã1003ã®ããããã®æ¹æ³ã
[æ¬çºæ1005]
GSK3çµè·¯é»å®³ç©è³ªãã6-ããã¢ã€ã³ãžã«ãã³-3'-ãªãã·ã ïŒBIOïŒãCHIR98014ïŒCHIR99021ïŒARA014418ïŒãã¡ãã¢ã«ãžã·ã³ïŒhymenialdisineïŒïŒãã©ãããªããŒã«ïŒã¢ãã€ãžã³AïŒã¢ãã€ãžã³BïŒCT20026ïŒSU9516ïŒã¹ã¿ãŠãã¹ããªã³ïŒGF109203xïŒRO318220ïŒSB216763ïŒSB415286ïŒI5ïŒCGP60474ïŒã±ã³ããŠãã³ïŒ9-ããã¢ããŠãã³ïŒïŒã¢ã«ã¹ã¿ãŒããŠãã³ïŒ2-ã·ã¢ããšãã«-ã¢ã«ã¹ã¿ãŒããŠãã³ïŒ1-ã¢ã¶-ã¢ã«ã¹ã¿ãŒããŠãã³ïŒ1-ã¢ã¶-ã±ã³ããŠãã³ïŒ9-ã·ã¢ã-2,3-ãžã¡ããã·ããŠãã³ïŒ2-ãšãŒãããŠãã³ïŒ2-ããã¢-9-ãããããŠãã³ïŒ2,3-ãžã¡ããã·-9-ãããããŠãã³ïŒ7-ããã¢-5-(4-ããããã§ãã«ããã©ãŸã)-4,5-ãžããã-1-H-[1]ãã³ãŸã¢ãŒãã³2(3H)-ãªã³ïŒ7,8-ãžã¡ããã·-5-(4-ããããã§ãã«ããã©ãŸã)-4,5ãžããã-1H-[1]ãã³ãŸã¢ãŒãã³-2-(3H)-ãªã³ïŒ9-ã·ã¢ãããŠãã³ïŒ9-ã¯ããããŠãã³ïŒ9-ããªãã«ãªãã¡ãã«ããŠãã³ïŒ2,3-ãžã¡ããã·-9-ããªãã«ãªãã¡ãã«ããŠãã³ïŒ9-ããã¢-12-ã¡ãã«ãªãã·ã«ã«ããã«ã¡ãã«ããŠãã³ïŒ9-ãã«ãªãããŠãã³ïŒ9-ããã¢-2,3-ãžã¡ããã·ããŠãã³ïŒ9-ããã¢-2,3-ãžã¡ããã·ããŠãã³ïŒ9-ã¡ãã«ããŠãã³ïŒ10-ããã¢ããŠãã³ïŒ2-ããã¢ããŠãã³ïŒ11-ã¯ããããŠãã³ïŒ2-(3-ããããã·-1-ããããã«)-9-ããªãã«ãªãã¡ãã«ããŠãã³ïŒ9-ããã¢-12-(2-ããããã·ãšãã«)-ããŠãã³ïŒã±ã³ããŠãã³ïŒã¢ã«ã¹ã¿ãŒããŠãã³ïŒ2-ã·ã¢ããšãã«-ã¢ã«ã¹ã¿ãŒããŠãã³ïŒ1-ã¢ã¶-ã±ã³ããŠãã³ïŒ1-ã¢ã¶-ã¢ã«ã¹ã¿ãŒããŠãã³ïŒ9-ããã¢-12-ã¡ãã«ããŠãã³ïŒ9-ããã¢-5-(ã¡ãã«ãªãã·ã«ã«ããã«ã¡ãã«)ããŠãã³ïŒ11-ã¡ãã«ããŠãã³ïŒããŠãã³ïŒ11-ãšãã«ããŠãã³ïŒ9-ããã¢-7,12-ãžããã-6-(ããããã·ã¢ãã)-ã€ã³ãã[2-3-d][1]ãã³ãŸã¢ãŒãã³ïŒ2,9-ãžããã¢ããŠãã³ïŒ11-ããã¢ããŠãã³ïŒ2,3-ãžã¡ããã·ããŠãã³ïŒ9-ããã¢-7,12ãžããã-6-ã¡ãã«ããª-ã€ã³ãã[2-3-d][1]ãã³ãŸã¢ãŒãã³ïŒ(E)-2(3-ãªããœ-1-ãããã«)-9-ããªãã«ãªãã¡ãã«ããŠãã³ïŒ9-ããã¢-12ãšãã«ããŠãã³ïŒ9-ããã¢-7,12-ãžããã-ã€ã³ãã[2-3-d][1]ãã³ãŸã¢ãŒãã³-6(5H)-ããªã³ïŒ2-ããã¢-9-ããªãã«ãªãã¡ãã«ããŠãã³ïŒ2-[2-(1-ããããã·ã·ã¯ãããã·ã«)ãšããã«]-9-ããªãã«ãªãã¡ãã«-ããŠãã³ïŒ9-ããã¢-5ã¡ãã«ããŠãã³ïŒ9-ã¡ããã·ããŠãã³ïŒ2-ãšãŒã-9-ããªãã«ãªãã¡ãã«ããŠãã³ïŒ9-ããã¢-12-(tert-ããã«ãªãã·ã«ã«ããã«)-ããŠãã³ïŒ9-ããã¢-12-(2-ããããã«)ããŠãã³ïŒ9-ããã¢-4-ããããã·ããŠãã³ïŒ8,10-ãžã¯ããããŠãã³ïŒ5-ãã³ãžã«-9-ããã¢ããŠãã³ïŒ9-ããã¢-4-ã¡ããã·ããŠãã³ïŒ9-ããã¢-5-ãšãã«ããŠãã³ïŒ9-ããã¢-5,7ãã¹-(tert-ããã«ãªãã·ã«ã«ããã«)-ããŠãã³ïŒ4-ã¡ããã·ããŠãã³ïŒ9-ããã¢-5,6,7,12-ããã©ããããã³ãŸ[6-7]ã·ã¯ãããã[1,2.b]ã€ã³ããŒã«ïŒ2-ãã§ãã«-4-(2-ããšãã«)-5H-ããªã[2-3d][1]ãã³ãŸã¢ãŒãã³-6(7H)-ããªã³ïŒ9-ããã¢-5,7,12-ããª-(tert-ããã«ãªãã·ã«ã«ããã«)-ããŠãã³ïŒ9-ããã¢-5,12-ãã¹-(tert-ããã«ãªãã·ã«ã«ããã«)ããŠãã³ïŒ4-(4-ã¯ãããã§ãã«)-2-(2-ãããã«)-5H-ããªã[23-d][1]ãã³ãŸã¢ãŒãã³-6(7H)-ããªã³ïŒ5,6,7,12-ããã©ããããã³ãŸ[6-7]ã·ã¯ãããã[1,2-b]ã€ã³ããŒã«ïŒN-ããã«-N'-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãŠã¬ã¢ïŒN-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãã³ã¿ã³ã¢ããïŒ1-{4-ã¢ãã-2-[(4-ã¡ããã·ãã§ãã«)ã¢ãã]-1,3-ãã¢ãŸãŒã«-5-ã€ã«}ãšã¿ãã³ïŒN-ãã³ãžã«-N'-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãŠã¬ã¢ïŒN-(4-ã¡ããã·ãã³ãžã«)-N'-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãŠã¬ã¢ïŒ3-(4-ã¡ããã·ãã§ãã«)-N-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãããã³ã¢ããïŒ4-(4-ã¡ããã·ãã§ãã«)-N-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãã¿ã³ã¢ããïŒ2-(3-ã¡ããã·ãã§ãã«)-N-(5-ããã-1,3-ãã¢ãŸãŒã«-2ã€ã«)ã¢ã»ãã¢ããïŒ2-(4-ãã«ãªããã§ãã«)-N-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãããã³ã¢ããïŒ2-(3-ã¡ãã«ãã§ãã«)-N-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ã¢ã»ãã¢ããïŒ1-ãã³ãžã«-3-ããã¿ã¬ã³-1-ã€ã«-ãŠã¬ã¢ãŸãã¯1-ãã³ãžã«[1,3]ãžãªããœãŒã«-5-ã€ã«-3-ãã³ãžã«-ãŠã¬ã¢ïŒããã³ãããã®ä»»æã®çµã¿åãããããªã矀ããéžæããããæ¬çºæ1001ã1004ã®ããããã®æ¹æ³ã
[æ¬çºæ1006]
GSK3çµè·¯é»å®³ç©è³ªã®æ¿åºŠããçŽ0.05ÎŒMãçŽ50ÎŒMã§ãããæ¬çºæ1001ã1005ã®ããããã®æ¹æ³ã
[æ¬çºæ1007]
cAMPã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ããã¢ãããªã«ã·ã¯ã©ãŒãŒã®æŽ»æ§åç©è³ªã§ãããæ¬çºæ1001ã1006ã®ããããã®æ¹æ³ã
[æ¬çºæ1008]
cAMPã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ãããã©ã«ã¹ã³ãªã³ïŒãã©ã«ã¹ã³ãªã³èªå°äœããã³ã¢ããã°ïŒcAMPã®éå æ°Žå解æ§ã¢ããã°ïŒã€ãœãããã¬ããŒã«ïŒisoprotenolïŒïŒè¡ç®¡äœåæ§è žç®¡ããããïŒã«ã«ã·ãŠã ã€ãªããã©ã¢ïŒèè±å極ïŒcAMPãåºæ¿ãããã¯ããã¡ãŒãžç±æ¥å åïŒãã¯ããã¡ãŒãžã®æŽ»æ§åãåºæ¿ããäœçšç©è³ªïŒãã¹ããžãšã¹ãã©ãŒãŒé»å®³ç©è³ªïŒäžåäœã¢ããã«é žã·ã¯ã©ãŒãŒæŽ»æ§åããããïŒPACAPïŒïŒã³ã¬ã©æ¯çŽ ïŒããã¹ã¿ã°ã©ã³ãžã³ååç©ïŒããŒã¿2-ã¢ãã¬ããªã³å容äœã¢ãŽãã¹ãïŒããã³ãããã®ä»»æã®çµã¿åãããããªã矀ããéžæããããæ¬çºæ1001ã1007ã®ããããã®æ¹æ³ã
[æ¬çºæ1009]
cAMPã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ã®æ¿åºŠããçŽ0.1ÎŒMãçŽ500ÎŒMã§ãããæ¬çºæ1001ã1008ã®ããããã®æ¹æ³ã
[æ¬çºæ1010]
FGFçµè·¯æŽ»æ§ç©è³ªãããã¹ãã¡ããžã«ã€ãã·ãã 3-ãããŒãŒïŒPI3KïŒPI3K掻æ§åç©è³ªã§ãããæ¬çºæ1001ã1009ã®ããããã®æ¹æ³ã
[æ¬çºæ1011]
FGFçµè·¯æŽ»æ§åç©è³ªããç·ç¶èœçŽ°èæé·å åïŒbFGFãFGF2ãŸãã¯FGF-βïŒïŒTGFαïŒTGFβïŒEGFïŒNGFïŒAkt掻æ§åç©è³ªïŒãã³ãã³ïŒã«ã«ãã³ãŒã«ïŒ4-(ã¡ãã«ããããœã¢ãã)-1-(3-ããªãžã«)-1-ãã¿ãã³ïŒNNKïŒïŒã¢ãã¬ãã¡ãã¥ãªã³ïŒãªãŸãã¹ãã¡ããžã³é žïŒè¡å°æ¿æŽ»æ§åå åïŒãã¯ããã¡ãŒãžåºæ¿å åïŒã¹ãã£ã³ãŽã·ã³-1-ãªã³é žïŒã€ã³ã¹ãªã³ããã³ã€ã³ã¹ãªã³æé·å å-1ïŒè¡å°æ¿ç±æ¥æé·å åïŒãªãã³ã«ãããã®ä»»æã®çµã¿åãããããªã矀ããéžæããããæ¬çºæ1001ã1000ã®ããããã®æ¹æ³ã
[æ¬çºæ1012]
FGFçµè·¯æŽ»æ§åç©è³ªã®æ¿åºŠããçŽ0.25 ng/mlãçŽ100 ng/mlã§ãããæ¬çºæ1001ã1011ã®ããããã®æ¹æ³ã
[æ¬çºæ1013]
GSK3çµè·¯é»å®³ç©è³ªãBIOã§ããã3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ããã©ã«ã¹ã³ãªã³ã§ããããã€FGFçµè·¯æŽ»æ§åç©è³ªãbFGFã§ãããæ¬çºæ1001ã1012ã®ããããã®æ¹æ³ã
[æ¬çºæ1014]
çå现èããéªšæ Œç圢æç³»èã®çŽ°èã§ãããæ¬çºæ1001ã1013ã®ããããã®æ¹æ³ã
[æ¬çºæ1015]
çå现èããPax3ãPax7ãMyoDãMyf5ãããªã²ãã³ãGATA2ãMHCããã³ãããã®ä»»æã®çµã¿åãããããªã矀ããéžæããã现èããŒã«ãŒãçºçŸãããæ¬çºæ1001ã1014ã®ããããã®æ¹æ³ã
[æ¬çºæ1016]
çå现èããäžèè现èã§ãããæ¬çºæ1001ã1015ã®ããããã®æ¹æ³ã
[æ¬çºæ1017]
æ¥è§Šã®åã«å¹¹çŽ°èããèæ§äœã圢æããå·¥çšãããã«å«ããæ¬çºæ1001ã1016ã®ããããã®æ¹æ³ã
[æ¬çºæ1018]
æ¥è§Šããå°ãªããšã1æ¥éè¡ããããæ¬çºæ1001ã1017ã®ããããã®æ¹æ³ã
[æ¬çºæ1019]
幹现èããæå·ããççµç¹ãŸãã¯çèéã®å¢å ã®åŠçœ®ãå¿ èŠãšãã察象ç±æ¥ã§ãããæ¬çºæ1001ã1018ã®ããããã®æ¹æ³ã
[æ¬çºæ1020]
æå·ããççµç¹ãã身äœçåå·ãŸãã¯äºæ ãçŸæ£ãææãé ·äœ¿ãè¡æ¶²åŸªç°ã®åªå€±ãŸãã¯çèçž®ãããã¯çæ¶èã®çµæã§ãããæ¬çºæ1019ã®æ¹æ³ã
[æ¬çºæ1021]
æ¬çºæ1001ã1020ã®ããããã®æ¹æ³ã«ããããçæãããçå现èã
[æ¬çºæ1022]
æ¬çºæ1001ã1020ã®ããããã®æ¹æ³ã®ããããã«ããããçæãããçå现èããã³è¬åŠçã«èš±å®¹ãããæ äœãå«ãè¬åŠççµæç©ã
[æ¬çºæ1023]
ïŒiïŒGSK3çµè·¯é»å®³ç©è³ªïŒïŒiiïŒ3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žïŒcAMPïŒã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ïŒããã³ïŒiiiïŒFGFçµè·¯æŽ»æ§åç©è³ªãã®å°ãªããšã2ã€ãå«ããçµæç©ã
[æ¬çºæ1024]
GSK3çµè·¯é»å®³ç©è³ªã3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ããã³FGFçµè·¯æŽ»æ§åç©è³ªãå«ããæ¬çºæ1023ã®çµæç©ã
[æ¬çºæ1025]
幹现èãããã«å«ããæ¬çºæ1023ãŸãã¯1024ã®çµæç©ã
[æ¬çºæ1026]
ïŒiïŒGSK3çµè·¯é»å®³ç©è³ªïŒïŒiiïŒ3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žïŒcAMPïŒã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ïŒããã³ïŒiiiïŒbFGFçµè·¯æŽ»æ§åç©è³ªãã®å°ãªããšã2ã€ãå«ãã现èå¹é€å¹å°ã
[æ¬çºæ1027]
GSK3çµè·¯é»å®³ç©è³ªã3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ããã³FGFçµè·¯æŽ»æ§åç©è³ªãå«ããæ¬çºæ1026ã®çŽ°èå¹é€å¹å°ã
[æ¬çºæ1028]
å€èœæ§å¹¹çŽ°èãããã«å«ããæ¬çºæ1006ãŸãã¯1027ã®çŽ°èå¹é€å¹å°ã
[æ¬çºæ1029]
ïŒiïŒGSK3çµè·¯é»å®³ç©è³ªïŒïŒiiïŒ3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žïŒcAMPïŒã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ïŒããã³ïŒiiiïŒFGFçµè·¯æŽ»æ§åç©è³ªãã®å°ãªããšã2ã€ãå«ããå€èœæ§çŽ°èããéªšæ Œçåé§çŽ°èãžã®ååãèªå°ããããã®è©Šè¬ãããã
[æ¬çºæ1030]
GSK3çµè·¯é»å®³ç©è³ªã3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ããã³FGFçµè·¯æŽ»æ§åç©è³ªãå«ããæ¬çºæ1029ã®ãããã
[æ¬çºæ1031]
幹现èãããã«å«ããæ¬çºæ1029ãŸãã¯1030ã®ãããã
[æ¬çºæ1032]
3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ã®ååšäžã§è¡æ现èãå¹é€ããå·¥çšãå«ããè¡æ现èã®å¢æ®ãå¢å ãããæ¹æ³ã
[æ¬çºæ1033]
該ååç©ãã¢ãããªã«ã·ã¯ã©ãŒãŒã®æŽ»æ§åç©è³ªã§ãããæ¬çºæ1032ã®æ¹æ³ã
[æ¬çºæ1034]
該ååç©ãããã©ã«ã¹ã³ãªã³ïŒãã©ã«ã¹ã³ãªã³èªå°äœããã³ã¢ããã°ïŒcAMPã®éå æ°Žå解æ§ã¢ããã°ïŒã€ãœãããã¬ããŒã«ïŒè¡ç®¡äœåæ§è žç®¡ããããïŒã«ã«ã·ãŠã ã€ãªããã©ã¢ïŒèè±å極ïŒcAMPãåºæ¿ãããã¯ããã¡ãŒãžç±æ¥å åïŒãã¯ããã¡ãŒãžã®æŽ»æ§åãåºæ¿ããäœçšç©è³ªïŒãã¹ããžãšã¹ãã©ãŒãŒé»å®³ç©è³ªïŒäžåäœã¢ããã«é žã·ã¯ã©ãŒãŒæŽ»æ§åããããïŒPACAPïŒïŒã³ã¬ã©æ¯çŽ ïŒããã¹ã¿ã°ã©ã³ãžã³ååç©ïŒããŒã¿2-ã¢ãã¬ããªã³å容äœã¢ãŽãã¹ãïŒããã³ãããã®ä»»æã®çµã¿åãããããªã矀ããéžæããããæ¬çºæ1032ãŸãã¯1033ã®æ¹æ³ã
[æ¬çºæ1035]
該ååç©ã®æ¿åºŠããçŽ0.01nMãçŽ100ÎŒMã§ãããæ¬çºæ1032ã1034ã®ããããã®æ¹æ³ã
[æ¬çºæ1036]
æ¥è§Šãå°ãªããšã1æ¥éã§ãããæ¬çºæ1032ã1035ã®ããããã®æ¹æ³ã
[æ¬çºæ1037]
è¡æ现èããæå·ããççµç¹ãŸãã¯çèéã®å¢å ã®åŠçœ®ãå¿ èŠãšãã察象ç±æ¥ã§ãããæ¬çºæ1032ã1036ã®ããããã®æ¹æ³ã
[æ¬çºæ1038]
æå·ããççµç¹ãã身äœçåå·ãŸãã¯äºæ ãçŸæ£ãææãé ·äœ¿ãè¡æ¶²åŸªç°ã®åªå€±ãŸãã¯çèçž®ãããã¯çæ¶èã®çµæã§ãããæ¬çºæ1037ã®æ¹æ³ã
[æ¬çºæ1039]
æ¬çºæ1032ã1038ã®ããããã®æ¹æ³ã«ããçæãããè¡æ现èã
[æ¬çºæ1040]
æ¬çºæ1032ã1038ã®ããããã®æ¹æ³ã«ããçæãããè¡æ现èããã³è¬åŠçã«èš±å®¹ãããæ äœãå«ãè¬åŠççµæç©ã
[æ¬çºæ1041]
æ¬çºæ1032ã1038ã®ããããã®æ¹æ³ã«ããããçæãããè¡æ现èã察象ã«æ€ã蟌ãå·¥çšãå«ãã察象ã«è¡æ现èã移æ€ããæ¹æ³ã
[æ¬çºæ1042]
æ¬çºæ1001ã1020ã®ããããã®æ¹æ³ã«ããããçæãããçå现èã察象ã«æ€ã蟌ãå·¥çšãå«ãã察象ã«çå现èã移æ€ããæ¹æ³ã
[æ¬çºæ1043]
察象ããæå·ããççµç¹ãŸãã¯çèéã®å¢å ã®åŠçœ®ãå¿ èŠãšããŠãããæ¬çºæ1041ãŸãã¯1042ã®æ¹æ³ã
[æ¬çºæ1044]
æå·ããççµç¹ãŸãã¯çèéã®å¢å ã®ããã«å¯Ÿè±¡ãåŠçœ®ããæ¹æ³ã§ãã£ãŠããããå¿ èŠãšãã察象ã«ãïŒiïŒGSK3çµè·¯é»å®³ç©è³ªïŒïŒiiïŒ3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žïŒcAMPïŒã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ïŒããã³ïŒiiiïŒFGFçµè·¯æŽ»æ§åç©è³ªãã®å°ãªããšã2ã€ãå ±æäžããå·¥çšãå«ããæ¹æ³ã
[æ¬çºæ1045]
ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã§ãã£ãŠãè©Šéšååç©ã®ååšäžã§å²çãå¹é€ããå·¥çšã§ãã£ãŠãå²çãã¬ããŒã¿ãŒéºäŒåãå«ã¿ãã¬ããŒã¿ãŒéºäŒåã现èç³»èç¹ç°çããŒã«ãŒãã³ãŒãããŠãããã€çºçŸããããšãã«æ€åºå¯èœãªã·ã°ãã«ãçæãããå·¥çšïŒããã³æ€åºå¯èœãªã·ã°ãã«ã枬å®ïŒæ€åºããå·¥çšã§ãã£ãŠãæ€åºå¯èœãªã·ã°ãã«ã®ã¬ãã«ãŸãã¯éã®å€åããè©Šéšååç©ã现èç³»èç¹ç°çããŒã«ãŒãçºçŸãã现èç³»èã®çºçãŸãã¯æ©èœã調æŽããããšã瀺ããå·¥çšããå«ããã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
[æ¬çºæ1046]
ã¬ããŒã¿ãŒéºäŒåããèå ã¿ã³ãã¯è³ªã«èåããã现èç³»èç¹ç°çããŒã«ãŒãå«ãèåã¿ã³ãã¯è³ªãã³ãŒããããæ¬çºæ1045ã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
[æ¬çºæ1047]
å²çã2ã€ã®ç°ãªãã¬ããŒã¿ãŒéºäŒåãå«ã¿ãåã¬ããŒã¿ãŒéºäŒåãç°ãªã现èç³»èç¹ç°çããŒã«ãŒãã³ãŒãããŠãããã€çºçŸããããšãã«æ€åºå¯èœãªã·ã°ãã«ãçæãããæ¬çºæ1045ãŸãã¯1046ã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
[æ¬çºæ1048]
å²çãããŒãã©ãã£ãã·ã¥ã®å²çã§ãããæ¬çºæ1045ã1047ã®ããããã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
[æ¬çºæ1049]
è©Šéšååç©ããææ©ãŸãã¯ç¡æ©äœååïŒãµãã«ãªã³ïŒãªãªãŽç³ïŒå€ç³ïŒããããïŒã¿ã³ãã¯è³ªïŒããããã¢ããã°ããã³èªå°äœïŒããããæš¡å£äœïŒæ žé žïŒæ žé žã¢ããã°ããã³èªå°äœïŒçç©ææããåŸãããæœåºç©ïŒåç©çµç¹ïŒå€©ç¶ã«ååšãããŸãã¯åææ§ã®çµæç©ïŒãªãã³ã«ãããã®ä»»æã®çµã¿åãããããªã矀ããéžæããããæ¬çºæ1045ã1048ã®ããããã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
[æ¬çºæ1050]
è©Šéšååç©ãã0.01nmãçŽ10mMã®æçµæ¿åºŠã§ã€ã³ãã¥ããŒãããããæ¬çºæ1045ã1049ã®ããããã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
[æ¬çºæ1051]
é«ã¹ã«ãŒãããã¹ã¯ãªãŒãã³ã°ïŒHTSïŒã¢ãã»ã€ã§ãããæ¬çºæ1045ã1040ã®ããããã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
[æ¬çºæ1052]
æ¬çºæ1045ã1051ã®ããããã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã«ãã£ãŠéžæãããååç©ã
[æ¬çºæ1001]
幹现èã®çå现èãžã®ååãèªå°ããæ¹æ³ã§ãã£ãŠãïŒiïŒGSK3çµè·¯é»å®³ç©è³ªïŒïŒiiïŒ3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žïŒcAMPïŒã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ïŒããã³ïŒiiiïŒFGFçµè·¯æŽ»æ§åç©è³ªãã®å°ãªããšã2ã€ãšå ±ã«å¹¹çŽ°èãå¹é€ããå·¥çšãå«ããæ¹æ³ã
[æ¬çºæ1002]
å¹é€ããå·¥çšããGSK3çµè·¯é»å®³ç©è³ªã3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ãããã³FGFçµè·¯æŽ»æ§åç©è³ªã®ååšäžã§è¡ããããæ¬çºæ1001ã®æ¹æ³ã
[æ¬çºæ1003]
幹现èãã人工å€èœæ§å¹¹ïŒiPSïŒçŽ°èãèæ§å¹¹ïŒESïŒçŽ°èãŸãã¯å€ååèœæ§å¹¹çŽ°èã§ãããæ¬çºæ1001ãŸãã¯1002ã®æ¹æ³ã
[æ¬çºæ1004]
GSK3çµè·¯é»å®³ç©è³ªããGSK3βé»å®³ç©è³ªã§ãããæ¬çºæ1001ã1003ã®ããããã®æ¹æ³ã
[æ¬çºæ1005]
GSK3çµè·¯é»å®³ç©è³ªãã6-ããã¢ã€ã³ãžã«ãã³-3'-ãªãã·ã ïŒBIOïŒãCHIR98014ïŒCHIR99021ïŒARA014418ïŒãã¡ãã¢ã«ãžã·ã³ïŒhymenialdisineïŒïŒãã©ãããªããŒã«ïŒã¢ãã€ãžã³AïŒã¢ãã€ãžã³BïŒCT20026ïŒSU9516ïŒã¹ã¿ãŠãã¹ããªã³ïŒGF109203xïŒRO318220ïŒSB216763ïŒSB415286ïŒI5ïŒCGP60474ïŒã±ã³ããŠãã³ïŒ9-ããã¢ããŠãã³ïŒïŒã¢ã«ã¹ã¿ãŒããŠãã³ïŒ2-ã·ã¢ããšãã«-ã¢ã«ã¹ã¿ãŒããŠãã³ïŒ1-ã¢ã¶-ã¢ã«ã¹ã¿ãŒããŠãã³ïŒ1-ã¢ã¶-ã±ã³ããŠãã³ïŒ9-ã·ã¢ã-2,3-ãžã¡ããã·ããŠãã³ïŒ2-ãšãŒãããŠãã³ïŒ2-ããã¢-9-ãããããŠãã³ïŒ2,3-ãžã¡ããã·-9-ãããããŠãã³ïŒ7-ããã¢-5-(4-ããããã§ãã«ããã©ãŸã)-4,5-ãžããã-1-H-[1]ãã³ãŸã¢ãŒãã³2(3H)-ãªã³ïŒ7,8-ãžã¡ããã·-5-(4-ããããã§ãã«ããã©ãŸã)-4,5ãžããã-1H-[1]ãã³ãŸã¢ãŒãã³-2-(3H)-ãªã³ïŒ9-ã·ã¢ãããŠãã³ïŒ9-ã¯ããããŠãã³ïŒ9-ããªãã«ãªãã¡ãã«ããŠãã³ïŒ2,3-ãžã¡ããã·-9-ããªãã«ãªãã¡ãã«ããŠãã³ïŒ9-ããã¢-12-ã¡ãã«ãªãã·ã«ã«ããã«ã¡ãã«ããŠãã³ïŒ9-ãã«ãªãããŠãã³ïŒ9-ããã¢-2,3-ãžã¡ããã·ããŠãã³ïŒ9-ããã¢-2,3-ãžã¡ããã·ããŠãã³ïŒ9-ã¡ãã«ããŠãã³ïŒ10-ããã¢ããŠãã³ïŒ2-ããã¢ããŠãã³ïŒ11-ã¯ããããŠãã³ïŒ2-(3-ããããã·-1-ããããã«)-9-ããªãã«ãªãã¡ãã«ããŠãã³ïŒ9-ããã¢-12-(2-ããããã·ãšãã«)-ããŠãã³ïŒã±ã³ããŠãã³ïŒã¢ã«ã¹ã¿ãŒããŠãã³ïŒ2-ã·ã¢ããšãã«-ã¢ã«ã¹ã¿ãŒããŠãã³ïŒ1-ã¢ã¶-ã±ã³ããŠãã³ïŒ1-ã¢ã¶-ã¢ã«ã¹ã¿ãŒããŠãã³ïŒ9-ããã¢-12-ã¡ãã«ããŠãã³ïŒ9-ããã¢-5-(ã¡ãã«ãªãã·ã«ã«ããã«ã¡ãã«)ããŠãã³ïŒ11-ã¡ãã«ããŠãã³ïŒããŠãã³ïŒ11-ãšãã«ããŠãã³ïŒ9-ããã¢-7,12-ãžããã-6-(ããããã·ã¢ãã)-ã€ã³ãã[2-3-d][1]ãã³ãŸã¢ãŒãã³ïŒ2,9-ãžããã¢ããŠãã³ïŒ11-ããã¢ããŠãã³ïŒ2,3-ãžã¡ããã·ããŠãã³ïŒ9-ããã¢-7,12ãžããã-6-ã¡ãã«ããª-ã€ã³ãã[2-3-d][1]ãã³ãŸã¢ãŒãã³ïŒ(E)-2(3-ãªããœ-1-ãããã«)-9-ããªãã«ãªãã¡ãã«ããŠãã³ïŒ9-ããã¢-12ãšãã«ããŠãã³ïŒ9-ããã¢-7,12-ãžããã-ã€ã³ãã[2-3-d][1]ãã³ãŸã¢ãŒãã³-6(5H)-ããªã³ïŒ2-ããã¢-9-ããªãã«ãªãã¡ãã«ããŠãã³ïŒ2-[2-(1-ããããã·ã·ã¯ãããã·ã«)ãšããã«]-9-ããªãã«ãªãã¡ãã«-ããŠãã³ïŒ9-ããã¢-5ã¡ãã«ããŠãã³ïŒ9-ã¡ããã·ããŠãã³ïŒ2-ãšãŒã-9-ããªãã«ãªãã¡ãã«ããŠãã³ïŒ9-ããã¢-12-(tert-ããã«ãªãã·ã«ã«ããã«)-ããŠãã³ïŒ9-ããã¢-12-(2-ããããã«)ããŠãã³ïŒ9-ããã¢-4-ããããã·ããŠãã³ïŒ8,10-ãžã¯ããããŠãã³ïŒ5-ãã³ãžã«-9-ããã¢ããŠãã³ïŒ9-ããã¢-4-ã¡ããã·ããŠãã³ïŒ9-ããã¢-5-ãšãã«ããŠãã³ïŒ9-ããã¢-5,7ãã¹-(tert-ããã«ãªãã·ã«ã«ããã«)-ããŠãã³ïŒ4-ã¡ããã·ããŠãã³ïŒ9-ããã¢-5,6,7,12-ããã©ããããã³ãŸ[6-7]ã·ã¯ãããã[1,2.b]ã€ã³ããŒã«ïŒ2-ãã§ãã«-4-(2-ããšãã«)-5H-ããªã[2-3d][1]ãã³ãŸã¢ãŒãã³-6(7H)-ããªã³ïŒ9-ããã¢-5,7,12-ããª-(tert-ããã«ãªãã·ã«ã«ããã«)-ããŠãã³ïŒ9-ããã¢-5,12-ãã¹-(tert-ããã«ãªãã·ã«ã«ããã«)ããŠãã³ïŒ4-(4-ã¯ãããã§ãã«)-2-(2-ãããã«)-5H-ããªã[23-d][1]ãã³ãŸã¢ãŒãã³-6(7H)-ããªã³ïŒ5,6,7,12-ããã©ããããã³ãŸ[6-7]ã·ã¯ãããã[1,2-b]ã€ã³ããŒã«ïŒN-ããã«-N'-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãŠã¬ã¢ïŒN-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãã³ã¿ã³ã¢ããïŒ1-{4-ã¢ãã-2-[(4-ã¡ããã·ãã§ãã«)ã¢ãã]-1,3-ãã¢ãŸãŒã«-5-ã€ã«}ãšã¿ãã³ïŒN-ãã³ãžã«-N'-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãŠã¬ã¢ïŒN-(4-ã¡ããã·ãã³ãžã«)-N'-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãŠã¬ã¢ïŒ3-(4-ã¡ããã·ãã§ãã«)-N-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãããã³ã¢ããïŒ4-(4-ã¡ããã·ãã§ãã«)-N-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãã¿ã³ã¢ããïŒ2-(3-ã¡ããã·ãã§ãã«)-N-(5-ããã-1,3-ãã¢ãŸãŒã«-2ã€ã«)ã¢ã»ãã¢ããïŒ2-(4-ãã«ãªããã§ãã«)-N-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãããã³ã¢ããïŒ2-(3-ã¡ãã«ãã§ãã«)-N-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ã¢ã»ãã¢ããïŒ1-ãã³ãžã«-3-ããã¿ã¬ã³-1-ã€ã«-ãŠã¬ã¢ãŸãã¯1-ãã³ãžã«[1,3]ãžãªããœãŒã«-5-ã€ã«-3-ãã³ãžã«-ãŠã¬ã¢ïŒããã³ãããã®ä»»æã®çµã¿åãããããªã矀ããéžæããããæ¬çºæ1001ã1004ã®ããããã®æ¹æ³ã
[æ¬çºæ1006]
GSK3çµè·¯é»å®³ç©è³ªã®æ¿åºŠããçŽ0.05ÎŒMãçŽ50ÎŒMã§ãããæ¬çºæ1001ã1005ã®ããããã®æ¹æ³ã
[æ¬çºæ1007]
cAMPã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ããã¢ãããªã«ã·ã¯ã©ãŒãŒã®æŽ»æ§åç©è³ªã§ãããæ¬çºæ1001ã1006ã®ããããã®æ¹æ³ã
[æ¬çºæ1008]
cAMPã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ãããã©ã«ã¹ã³ãªã³ïŒãã©ã«ã¹ã³ãªã³èªå°äœããã³ã¢ããã°ïŒcAMPã®éå æ°Žå解æ§ã¢ããã°ïŒã€ãœãããã¬ããŒã«ïŒisoprotenolïŒïŒè¡ç®¡äœåæ§è žç®¡ããããïŒã«ã«ã·ãŠã ã€ãªããã©ã¢ïŒèè±å極ïŒcAMPãåºæ¿ãããã¯ããã¡ãŒãžç±æ¥å åïŒãã¯ããã¡ãŒãžã®æŽ»æ§åãåºæ¿ããäœçšç©è³ªïŒãã¹ããžãšã¹ãã©ãŒãŒé»å®³ç©è³ªïŒäžåäœã¢ããã«é žã·ã¯ã©ãŒãŒæŽ»æ§åããããïŒPACAPïŒïŒã³ã¬ã©æ¯çŽ ïŒããã¹ã¿ã°ã©ã³ãžã³ååç©ïŒããŒã¿2-ã¢ãã¬ããªã³å容äœã¢ãŽãã¹ãïŒããã³ãããã®ä»»æã®çµã¿åãããããªã矀ããéžæããããæ¬çºæ1001ã1007ã®ããããã®æ¹æ³ã
[æ¬çºæ1009]
cAMPã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ã®æ¿åºŠããçŽ0.1ÎŒMãçŽ500ÎŒMã§ãããæ¬çºæ1001ã1008ã®ããããã®æ¹æ³ã
[æ¬çºæ1010]
FGFçµè·¯æŽ»æ§ç©è³ªãããã¹ãã¡ããžã«ã€ãã·ãã 3-ãããŒãŒïŒPI3KïŒPI3K掻æ§åç©è³ªã§ãããæ¬çºæ1001ã1009ã®ããããã®æ¹æ³ã
[æ¬çºæ1011]
FGFçµè·¯æŽ»æ§åç©è³ªããç·ç¶èœçŽ°èæé·å åïŒbFGFãFGF2ãŸãã¯FGF-βïŒïŒTGFαïŒTGFβïŒEGFïŒNGFïŒAkt掻æ§åç©è³ªïŒãã³ãã³ïŒã«ã«ãã³ãŒã«ïŒ4-(ã¡ãã«ããããœã¢ãã)-1-(3-ããªãžã«)-1-ãã¿ãã³ïŒNNKïŒïŒã¢ãã¬ãã¡ãã¥ãªã³ïŒãªãŸãã¹ãã¡ããžã³é žïŒè¡å°æ¿æŽ»æ§åå åïŒãã¯ããã¡ãŒãžåºæ¿å åïŒã¹ãã£ã³ãŽã·ã³-1-ãªã³é žïŒã€ã³ã¹ãªã³ããã³ã€ã³ã¹ãªã³æé·å å-1ïŒè¡å°æ¿ç±æ¥æé·å åïŒãªãã³ã«ãããã®ä»»æã®çµã¿åãããããªã矀ããéžæããããæ¬çºæ1001ã1000ã®ããããã®æ¹æ³ã
[æ¬çºæ1012]
FGFçµè·¯æŽ»æ§åç©è³ªã®æ¿åºŠããçŽ0.25 ng/mlãçŽ100 ng/mlã§ãããæ¬çºæ1001ã1011ã®ããããã®æ¹æ³ã
[æ¬çºæ1013]
GSK3çµè·¯é»å®³ç©è³ªãBIOã§ããã3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ããã©ã«ã¹ã³ãªã³ã§ããããã€FGFçµè·¯æŽ»æ§åç©è³ªãbFGFã§ãããæ¬çºæ1001ã1012ã®ããããã®æ¹æ³ã
[æ¬çºæ1014]
çå现èããéªšæ Œç圢æç³»èã®çŽ°èã§ãããæ¬çºæ1001ã1013ã®ããããã®æ¹æ³ã
[æ¬çºæ1015]
çå现èããPax3ãPax7ãMyoDãMyf5ãããªã²ãã³ãGATA2ãMHCããã³ãããã®ä»»æã®çµã¿åãããããªã矀ããéžæããã现èããŒã«ãŒãçºçŸãããæ¬çºæ1001ã1014ã®ããããã®æ¹æ³ã
[æ¬çºæ1016]
çå现èããäžèè现èã§ãããæ¬çºæ1001ã1015ã®ããããã®æ¹æ³ã
[æ¬çºæ1017]
æ¥è§Šã®åã«å¹¹çŽ°èããèæ§äœã圢æããå·¥çšãããã«å«ããæ¬çºæ1001ã1016ã®ããããã®æ¹æ³ã
[æ¬çºæ1018]
æ¥è§Šããå°ãªããšã1æ¥éè¡ããããæ¬çºæ1001ã1017ã®ããããã®æ¹æ³ã
[æ¬çºæ1019]
幹现èããæå·ããççµç¹ãŸãã¯çèéã®å¢å ã®åŠçœ®ãå¿ èŠãšãã察象ç±æ¥ã§ãããæ¬çºæ1001ã1018ã®ããããã®æ¹æ³ã
[æ¬çºæ1020]
æå·ããççµç¹ãã身äœçåå·ãŸãã¯äºæ ãçŸæ£ãææãé ·äœ¿ãè¡æ¶²åŸªç°ã®åªå€±ãŸãã¯çèçž®ãããã¯çæ¶èã®çµæã§ãããæ¬çºæ1019ã®æ¹æ³ã
[æ¬çºæ1021]
æ¬çºæ1001ã1020ã®ããããã®æ¹æ³ã«ããããçæãããçå现èã
[æ¬çºæ1022]
æ¬çºæ1001ã1020ã®ããããã®æ¹æ³ã®ããããã«ããããçæãããçå现èããã³è¬åŠçã«èš±å®¹ãããæ äœãå«ãè¬åŠççµæç©ã
[æ¬çºæ1023]
ïŒiïŒGSK3çµè·¯é»å®³ç©è³ªïŒïŒiiïŒ3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žïŒcAMPïŒã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ïŒããã³ïŒiiiïŒFGFçµè·¯æŽ»æ§åç©è³ªãã®å°ãªããšã2ã€ãå«ããçµæç©ã
[æ¬çºæ1024]
GSK3çµè·¯é»å®³ç©è³ªã3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ããã³FGFçµè·¯æŽ»æ§åç©è³ªãå«ããæ¬çºæ1023ã®çµæç©ã
[æ¬çºæ1025]
幹现èãããã«å«ããæ¬çºæ1023ãŸãã¯1024ã®çµæç©ã
[æ¬çºæ1026]
ïŒiïŒGSK3çµè·¯é»å®³ç©è³ªïŒïŒiiïŒ3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žïŒcAMPïŒã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ïŒããã³ïŒiiiïŒbFGFçµè·¯æŽ»æ§åç©è³ªãã®å°ãªããšã2ã€ãå«ãã现èå¹é€å¹å°ã
[æ¬çºæ1027]
GSK3çµè·¯é»å®³ç©è³ªã3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ããã³FGFçµè·¯æŽ»æ§åç©è³ªãå«ããæ¬çºæ1026ã®çŽ°èå¹é€å¹å°ã
[æ¬çºæ1028]
å€èœæ§å¹¹çŽ°èãããã«å«ããæ¬çºæ1006ãŸãã¯1027ã®çŽ°èå¹é€å¹å°ã
[æ¬çºæ1029]
ïŒiïŒGSK3çµè·¯é»å®³ç©è³ªïŒïŒiiïŒ3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žïŒcAMPïŒã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ïŒããã³ïŒiiiïŒFGFçµè·¯æŽ»æ§åç©è³ªãã®å°ãªããšã2ã€ãå«ããå€èœæ§çŽ°èããéªšæ Œçåé§çŽ°èãžã®ååãèªå°ããããã®è©Šè¬ãããã
[æ¬çºæ1030]
GSK3çµè·¯é»å®³ç©è³ªã3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ããã³FGFçµè·¯æŽ»æ§åç©è³ªãå«ããæ¬çºæ1029ã®ãããã
[æ¬çºæ1031]
幹现èãããã«å«ããæ¬çºæ1029ãŸãã¯1030ã®ãããã
[æ¬çºæ1032]
3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ã®ååšäžã§è¡æ现èãå¹é€ããå·¥çšãå«ããè¡æ现èã®å¢æ®ãå¢å ãããæ¹æ³ã
[æ¬çºæ1033]
該ååç©ãã¢ãããªã«ã·ã¯ã©ãŒãŒã®æŽ»æ§åç©è³ªã§ãããæ¬çºæ1032ã®æ¹æ³ã
[æ¬çºæ1034]
該ååç©ãããã©ã«ã¹ã³ãªã³ïŒãã©ã«ã¹ã³ãªã³èªå°äœããã³ã¢ããã°ïŒcAMPã®éå æ°Žå解æ§ã¢ããã°ïŒã€ãœãããã¬ããŒã«ïŒè¡ç®¡äœåæ§è žç®¡ããããïŒã«ã«ã·ãŠã ã€ãªããã©ã¢ïŒèè±å極ïŒcAMPãåºæ¿ãããã¯ããã¡ãŒãžç±æ¥å åïŒãã¯ããã¡ãŒãžã®æŽ»æ§åãåºæ¿ããäœçšç©è³ªïŒãã¹ããžãšã¹ãã©ãŒãŒé»å®³ç©è³ªïŒäžåäœã¢ããã«é žã·ã¯ã©ãŒãŒæŽ»æ§åããããïŒPACAPïŒïŒã³ã¬ã©æ¯çŽ ïŒããã¹ã¿ã°ã©ã³ãžã³ååç©ïŒããŒã¿2-ã¢ãã¬ããªã³å容äœã¢ãŽãã¹ãïŒããã³ãããã®ä»»æã®çµã¿åãããããªã矀ããéžæããããæ¬çºæ1032ãŸãã¯1033ã®æ¹æ³ã
[æ¬çºæ1035]
該ååç©ã®æ¿åºŠããçŽ0.01nMãçŽ100ÎŒMã§ãããæ¬çºæ1032ã1034ã®ããããã®æ¹æ³ã
[æ¬çºæ1036]
æ¥è§Šãå°ãªããšã1æ¥éã§ãããæ¬çºæ1032ã1035ã®ããããã®æ¹æ³ã
[æ¬çºæ1037]
è¡æ现èããæå·ããççµç¹ãŸãã¯çèéã®å¢å ã®åŠçœ®ãå¿ èŠãšãã察象ç±æ¥ã§ãããæ¬çºæ1032ã1036ã®ããããã®æ¹æ³ã
[æ¬çºæ1038]
æå·ããççµç¹ãã身äœçåå·ãŸãã¯äºæ ãçŸæ£ãææãé ·äœ¿ãè¡æ¶²åŸªç°ã®åªå€±ãŸãã¯çèçž®ãããã¯çæ¶èã®çµæã§ãããæ¬çºæ1037ã®æ¹æ³ã
[æ¬çºæ1039]
æ¬çºæ1032ã1038ã®ããããã®æ¹æ³ã«ããçæãããè¡æ现èã
[æ¬çºæ1040]
æ¬çºæ1032ã1038ã®ããããã®æ¹æ³ã«ããçæãããè¡æ现èããã³è¬åŠçã«èš±å®¹ãããæ äœãå«ãè¬åŠççµæç©ã
[æ¬çºæ1041]
æ¬çºæ1032ã1038ã®ããããã®æ¹æ³ã«ããããçæãããè¡æ现èã察象ã«æ€ã蟌ãå·¥çšãå«ãã察象ã«è¡æ现èã移æ€ããæ¹æ³ã
[æ¬çºæ1042]
æ¬çºæ1001ã1020ã®ããããã®æ¹æ³ã«ããããçæãããçå现èã察象ã«æ€ã蟌ãå·¥çšãå«ãã察象ã«çå现èã移æ€ããæ¹æ³ã
[æ¬çºæ1043]
察象ããæå·ããççµç¹ãŸãã¯çèéã®å¢å ã®åŠçœ®ãå¿ èŠãšããŠãããæ¬çºæ1041ãŸãã¯1042ã®æ¹æ³ã
[æ¬çºæ1044]
æå·ããççµç¹ãŸãã¯çèéã®å¢å ã®ããã«å¯Ÿè±¡ãåŠçœ®ããæ¹æ³ã§ãã£ãŠããããå¿ èŠãšãã察象ã«ãïŒiïŒGSK3çµè·¯é»å®³ç©è³ªïŒïŒiiïŒ3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žïŒcAMPïŒã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ïŒããã³ïŒiiiïŒFGFçµè·¯æŽ»æ§åç©è³ªãã®å°ãªããšã2ã€ãå ±æäžããå·¥çšãå«ããæ¹æ³ã
[æ¬çºæ1045]
ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã§ãã£ãŠãè©Šéšååç©ã®ååšäžã§å²çãå¹é€ããå·¥çšã§ãã£ãŠãå²çãã¬ããŒã¿ãŒéºäŒåãå«ã¿ãã¬ããŒã¿ãŒéºäŒåã现èç³»èç¹ç°çããŒã«ãŒãã³ãŒãããŠãããã€çºçŸããããšãã«æ€åºå¯èœãªã·ã°ãã«ãçæãããå·¥çšïŒããã³æ€åºå¯èœãªã·ã°ãã«ã枬å®ïŒæ€åºããå·¥çšã§ãã£ãŠãæ€åºå¯èœãªã·ã°ãã«ã®ã¬ãã«ãŸãã¯éã®å€åããè©Šéšååç©ã现èç³»èç¹ç°çããŒã«ãŒãçºçŸãã现èç³»èã®çºçãŸãã¯æ©èœã調æŽããããšã瀺ããå·¥çšããå«ããã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
[æ¬çºæ1046]
ã¬ããŒã¿ãŒéºäŒåããèå ã¿ã³ãã¯è³ªã«èåããã现èç³»èç¹ç°çããŒã«ãŒãå«ãèåã¿ã³ãã¯è³ªãã³ãŒããããæ¬çºæ1045ã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
[æ¬çºæ1047]
å²çã2ã€ã®ç°ãªãã¬ããŒã¿ãŒéºäŒåãå«ã¿ãåã¬ããŒã¿ãŒéºäŒåãç°ãªã现èç³»èç¹ç°çããŒã«ãŒãã³ãŒãããŠãããã€çºçŸããããšãã«æ€åºå¯èœãªã·ã°ãã«ãçæãããæ¬çºæ1045ãŸãã¯1046ã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
[æ¬çºæ1048]
å²çãããŒãã©ãã£ãã·ã¥ã®å²çã§ãããæ¬çºæ1045ã1047ã®ããããã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
[æ¬çºæ1049]
è©Šéšååç©ããææ©ãŸãã¯ç¡æ©äœååïŒãµãã«ãªã³ïŒãªãªãŽç³ïŒå€ç³ïŒããããïŒã¿ã³ãã¯è³ªïŒããããã¢ããã°ããã³èªå°äœïŒããããæš¡å£äœïŒæ žé žïŒæ žé žã¢ããã°ããã³èªå°äœïŒçç©ææããåŸãããæœåºç©ïŒåç©çµç¹ïŒå€©ç¶ã«ååšãããŸãã¯åææ§ã®çµæç©ïŒãªãã³ã«ãããã®ä»»æã®çµã¿åãããããªã矀ããéžæããããæ¬çºæ1045ã1048ã®ããããã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
[æ¬çºæ1050]
è©Šéšååç©ãã0.01nmãçŽ10mMã®æçµæ¿åºŠã§ã€ã³ãã¥ããŒãããããæ¬çºæ1045ã1049ã®ããããã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
[æ¬çºæ1051]
é«ã¹ã«ãŒãããã¹ã¯ãªãŒãã³ã°ïŒHTSïŒã¢ãã»ã€ã§ãããæ¬çºæ1045ã1040ã®ããããã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
[æ¬çºæ1052]
æ¬çºæ1045ã1051ã®ããããã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã«ãã£ãŠéžæãããååç©ã
Claims (52)
- 幹现èã®çå现èãžã®ååãèªå°ããæ¹æ³ã§ãã£ãŠãïŒiïŒGSK3çµè·¯é»å®³ç©è³ªïŒïŒiiïŒ3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žïŒcAMPïŒã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ïŒããã³ïŒiiiïŒFGFçµè·¯æŽ»æ§åç©è³ªãã®å°ãªããšã2ã€ãšå ±ã«å¹¹çŽ°èãå¹é€ããå·¥çšãå«ããæ¹æ³ã
- å¹é€ããå·¥çšããGSK3çµè·¯é»å®³ç©è³ªã3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ãããã³FGFçµè·¯æŽ»æ§åç©è³ªã®ååšäžã§è¡ããããè«æ±é 1èšèŒã®æ¹æ³ã
- 幹现èãã人工å€èœæ§å¹¹ïŒiPSïŒçŽ°èãèæ§å¹¹ïŒESïŒçŽ°èãŸãã¯å€ååèœæ§å¹¹çŽ°èã§ãããè«æ±é 1ãŸãã¯2èšèŒã®æ¹æ³ã
- GSK3çµè·¯é»å®³ç©è³ªããGSK3βé»å®³ç©è³ªã§ãããè«æ±é 1ã3ã®ããããäžé èšèŒã®æ¹æ³ã
- GSK3çµè·¯é»å®³ç©è³ªãã6-ããã¢ã€ã³ãžã«ãã³-3'-ãªãã·ã ïŒBIOïŒãCHIR98014ïŒCHIR99021ïŒARA014418ïŒãã¡ãã¢ã«ãžã·ã³ïŒhymenialdisineïŒïŒãã©ãããªããŒã«ïŒã¢ãã€ãžã³AïŒã¢ãã€ãžã³BïŒCT20026ïŒSU9516ïŒã¹ã¿ãŠãã¹ããªã³ïŒGF109203xïŒRO318220ïŒSB216763ïŒSB415286ïŒI5ïŒCGP60474ïŒã±ã³ããŠãã³ïŒ9-ããã¢ããŠãã³ïŒïŒã¢ã«ã¹ã¿ãŒããŠãã³ïŒ2-ã·ã¢ããšãã«-ã¢ã«ã¹ã¿ãŒããŠãã³ïŒ1-ã¢ã¶-ã¢ã«ã¹ã¿ãŒããŠãã³ïŒ1-ã¢ã¶-ã±ã³ããŠãã³ïŒ9-ã·ã¢ã-2,3-ãžã¡ããã·ããŠãã³ïŒ2-ãšãŒãããŠãã³ïŒ2-ããã¢-9-ãããããŠãã³ïŒ2,3-ãžã¡ããã·-9-ãããããŠãã³ïŒ7-ããã¢-5-(4-ããããã§ãã«ããã©ãŸã)-4,5-ãžããã-1-H-[1]ãã³ãŸã¢ãŒãã³2(3H)-ãªã³ïŒ7,8-ãžã¡ããã·-5-(4-ããããã§ãã«ããã©ãŸã)-4,5ãžããã-1H-[1]ãã³ãŸã¢ãŒãã³-2-(3H)-ãªã³ïŒ9-ã·ã¢ãããŠãã³ïŒ9-ã¯ããããŠãã³ïŒ9-ããªãã«ãªãã¡ãã«ããŠãã³ïŒ2,3-ãžã¡ããã·-9-ããªãã«ãªãã¡ãã«ããŠãã³ïŒ9-ããã¢-12-ã¡ãã«ãªãã·ã«ã«ããã«ã¡ãã«ããŠãã³ïŒ9-ãã«ãªãããŠãã³ïŒ9-ããã¢-2,3-ãžã¡ããã·ããŠãã³ïŒ9-ããã¢-2,3-ãžã¡ããã·ããŠãã³ïŒ9-ã¡ãã«ããŠãã³ïŒ10-ããã¢ããŠãã³ïŒ2-ããã¢ããŠãã³ïŒ11-ã¯ããããŠãã³ïŒ2-(3-ããããã·-1-ããããã«)-9-ããªãã«ãªãã¡ãã«ããŠãã³ïŒ9-ããã¢-12-(2-ããããã·ãšãã«)-ããŠãã³ïŒã±ã³ããŠãã³ïŒã¢ã«ã¹ã¿ãŒããŠãã³ïŒ2-ã·ã¢ããšãã«-ã¢ã«ã¹ã¿ãŒããŠãã³ïŒ1-ã¢ã¶-ã±ã³ããŠãã³ïŒ1-ã¢ã¶-ã¢ã«ã¹ã¿ãŒããŠãã³ïŒ9-ããã¢-12-ã¡ãã«ããŠãã³ïŒ9-ããã¢-5-(ã¡ãã«ãªãã·ã«ã«ããã«ã¡ãã«)ããŠãã³ïŒ11-ã¡ãã«ããŠãã³ïŒããŠãã³ïŒ11-ãšãã«ããŠãã³ïŒ9-ããã¢-7,12-ãžããã-6-(ããããã·ã¢ãã)-ã€ã³ãã[2-3-d][1]ãã³ãŸã¢ãŒãã³ïŒ2,9-ãžããã¢ããŠãã³ïŒ11-ããã¢ããŠãã³ïŒ2,3-ãžã¡ããã·ããŠãã³ïŒ9-ããã¢-7,12ãžããã-6-ã¡ãã«ããª-ã€ã³ãã[2-3-d][1]ãã³ãŸã¢ãŒãã³ïŒ(E)-2(3-ãªããœ-1-ãããã«)-9-ããªãã«ãªãã¡ãã«ããŠãã³ïŒ9-ããã¢-12ãšãã«ããŠãã³ïŒ9-ããã¢-7,12-ãžããã-ã€ã³ãã[2-3-d][1]ãã³ãŸã¢ãŒãã³-6(5H)-ããªã³ïŒ2-ããã¢-9-ããªãã«ãªãã¡ãã«ããŠãã³ïŒ2-[2-(1-ããããã·ã·ã¯ãããã·ã«)ãšããã«]-9-ããªãã«ãªãã¡ãã«-ããŠãã³ïŒ9-ããã¢-5ã¡ãã«ããŠãã³ïŒ9-ã¡ããã·ããŠãã³ïŒ2-ãšãŒã-9-ããªãã«ãªãã¡ãã«ããŠãã³ïŒ9-ããã¢-12-(tert-ããã«ãªãã·ã«ã«ããã«)-ããŠãã³ïŒ9-ããã¢-12-(2-ããããã«)ããŠãã³ïŒ9-ããã¢-4-ããããã·ããŠãã³ïŒ8,10-ãžã¯ããããŠãã³ïŒ5-ãã³ãžã«-9-ããã¢ããŠãã³ïŒ9-ããã¢-4-ã¡ããã·ããŠãã³ïŒ9-ããã¢-5-ãšãã«ããŠãã³ïŒ9-ããã¢-5,7ãã¹-(tert-ããã«ãªãã·ã«ã«ããã«)-ããŠãã³ïŒ4-ã¡ããã·ããŠãã³ïŒ9-ããã¢-5,6,7,12-ããã©ããããã³ãŸ[6-7]ã·ã¯ãããã[1,2.b]ã€ã³ããŒã«ïŒ2-ãã§ãã«-4-(2-ããšãã«)-5H-ããªã[2-3d][1]ãã³ãŸã¢ãŒãã³-6(7H)-ããªã³ïŒ9-ããã¢-5,7,12-ããª-(tert-ããã«ãªãã·ã«ã«ããã«)-ããŠãã³ïŒ9-ããã¢-5,12-ãã¹-(tert-ããã«ãªãã·ã«ã«ããã«)ããŠãã³ïŒ4-(4-ã¯ãããã§ãã«)-2-(2-ãããã«)-5H-ããªã[23-d][1]ãã³ãŸã¢ãŒãã³-6(7H)-ããªã³ïŒ5,6,7,12-ããã©ããããã³ãŸ[6-7]ã·ã¯ãããã[1,2-b]ã€ã³ããŒã«ïŒN-ããã«-N'-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãŠã¬ã¢ïŒN-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãã³ã¿ã³ã¢ããïŒ1-{4-ã¢ãã-2-[(4-ã¡ããã·ãã§ãã«)ã¢ãã]-1,3-ãã¢ãŸãŒã«-5-ã€ã«}ãšã¿ãã³ïŒN-ãã³ãžã«-N'-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãŠã¬ã¢ïŒN-(4-ã¡ããã·ãã³ãžã«)-N'-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãŠã¬ã¢ïŒ3-(4-ã¡ããã·ãã§ãã«)-N-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãããã³ã¢ããïŒ4-(4-ã¡ããã·ãã§ãã«)-N-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãã¿ã³ã¢ããïŒ2-(3-ã¡ããã·ãã§ãã«)-N-(5-ããã-1,3-ãã¢ãŸãŒã«-2ã€ã«)ã¢ã»ãã¢ããïŒ2-(4-ãã«ãªããã§ãã«)-N-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ãããã³ã¢ããïŒ2-(3-ã¡ãã«ãã§ãã«)-N-(5-ããã-1,3-ãã¢ãŸãŒã«-2-ã€ã«)ã¢ã»ãã¢ããïŒ1-ãã³ãžã«-3-ããã¿ã¬ã³-1-ã€ã«-ãŠã¬ã¢ãŸãã¯1-ãã³ãžã«[1,3]ãžãªããœãŒã«-5-ã€ã«-3-ãã³ãžã«-ãŠã¬ã¢ïŒããã³ãããã®ä»»æã®çµã¿åãããããªã矀ããéžæããããè«æ±é 1ã4ã®ããããäžé èšèŒã®æ¹æ³ã
- GSK3çµè·¯é»å®³ç©è³ªã®æ¿åºŠããçŽ0.05ÎŒMãçŽ50ÎŒMã§ãããè«æ±é 1ã5ã®ããããäžé èšèŒã®æ¹æ³ã
- cAMPã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ããã¢ãããªã«ã·ã¯ã©ãŒãŒã®æŽ»æ§åç©è³ªã§ãããè«æ±é 1ã6ã®ããããäžé èšèŒã®æ¹æ³ã
- cAMPã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ãããã©ã«ã¹ã³ãªã³ïŒãã©ã«ã¹ã³ãªã³èªå°äœããã³ã¢ããã°ïŒcAMPã®éå æ°Žå解æ§ã¢ããã°ïŒã€ãœãããã¬ããŒã«ïŒisoprotenolïŒïŒè¡ç®¡äœåæ§è žç®¡ããããïŒã«ã«ã·ãŠã ã€ãªããã©ã¢ïŒèè±å極ïŒcAMPãåºæ¿ãããã¯ããã¡ãŒãžç±æ¥å åïŒãã¯ããã¡ãŒãžã®æŽ»æ§åãåºæ¿ããäœçšç©è³ªïŒãã¹ããžãšã¹ãã©ãŒãŒé»å®³ç©è³ªïŒäžåäœã¢ããã«é žã·ã¯ã©ãŒãŒæŽ»æ§åããããïŒPACAPïŒïŒã³ã¬ã©æ¯çŽ ïŒããã¹ã¿ã°ã©ã³ãžã³ååç©ïŒããŒã¿2-ã¢ãã¬ããªã³å容äœã¢ãŽãã¹ãïŒããã³ãããã®ä»»æã®çµã¿åãããããªã矀ããéžæããããè«æ±é 1ã7ã®ããããäžé èšèŒã®æ¹æ³ã
- cAMPã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ã®æ¿åºŠããçŽ0.1ÎŒMãçŽ500ÎŒMã§ãããè«æ±é 1ã8ã®ããããäžé èšèŒã®æ¹æ³ã
- FGFçµè·¯æŽ»æ§åç©è³ªãããã¹ãã¡ããžã«ã€ãã·ãã 3-ãããŒãŒïŒPI3KïŒPI3K掻æ§åç©è³ªã§ãããè«æ±é 1ã9ã®ããããäžé èšèŒã®æ¹æ³ã
- FGFçµè·¯æŽ»æ§åç©è³ªããç·ç¶èœçŽ°èæé·å åïŒbFGFãFGF2ãŸãã¯FGF-βïŒïŒTGFαïŒTGFβïŒEGFïŒNGFïŒAkt掻æ§åç©è³ªïŒãã³ãã³ïŒã«ã«ãã³ãŒã«ïŒ4-(ã¡ãã«ããããœã¢ãã)-1-(3-ããªãžã«)-1-ãã¿ãã³ïŒNNKïŒïŒã¢ãã¬ãã¡ãã¥ãªã³ïŒãªãŸãã¹ãã¡ããžã³é žïŒè¡å°æ¿æŽ»æ§åå åïŒãã¯ããã¡ãŒãžåºæ¿å åïŒã¹ãã£ã³ãŽã·ã³-1-ãªã³é žïŒã€ã³ã¹ãªã³ããã³ã€ã³ã¹ãªã³æé·å å-1ïŒè¡å°æ¿ç±æ¥æé·å åïŒãªãã³ã«ãããã®ä»»æã®çµã¿åãããããªã矀ããéžæããããè«æ±é 1ã10ã®ããããäžé èšèŒã®æ¹æ³ã
- FGFçµè·¯æŽ»æ§åç©è³ªã®æ¿åºŠããçŽ0.25 ng/mlãçŽ100 ng/mlã§ãããè«æ±é 1ã11ã®ããããäžé èšèŒã®æ¹æ³ã
- GSK3çµè·¯é»å®³ç©è³ªãBIOã§ããã3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ããã©ã«ã¹ã³ãªã³ã§ããããã€FGFçµè·¯æŽ»æ§åç©è³ªãbFGFã§ãããè«æ±é 1ã12ã®ããããäžé èšèŒã®æ¹æ³ã
- çå现èããéªšæ Œç圢æç³»èã®çŽ°èã§ãããè«æ±é 1ã13ã®ããããäžé èšèŒã®æ¹æ³ã
- çå现èããPax3ãPax7ãMyoDãMyf5ãããªã²ãã³ãGATA2ãMHCããã³ãããã®ä»»æã®çµã¿åãããããªã矀ããéžæããã现èããŒã«ãŒãçºçŸãããè«æ±é 1ã14ã®ããããäžé èšèŒã®æ¹æ³ã
- çå现èããäžèè现èã§ãããè«æ±é 1ã15ã®ããããäžé èšèŒã®æ¹æ³ã
- æ¥è§Šã®åã«å¹¹çŽ°èããèæ§äœã圢æããå·¥çšãããã«å«ããè«æ±é 1ã16ã®ããããäžé èšèŒã®æ¹æ³ã
- æ¥è§Šããå°ãªããšã1æ¥éè¡ããããè«æ±é 1ã17ã®ããããäžé èšèŒã®æ¹æ³ã
- 幹现èããæå·ããççµç¹ãŸãã¯çèéã®å¢å ã®åŠçœ®ãå¿ èŠãšãã察象ç±æ¥ã§ãããè«æ±é 1ã18ã®ããããäžé èšèŒã®æ¹æ³ã
- æå·ããççµç¹ãã身äœçåå·ãŸãã¯äºæ ãçŸæ£ãææãé ·äœ¿ãè¡æ¶²åŸªç°ã®åªå€±ãŸãã¯çèçž®ãããã¯çæ¶èã®çµæã§ãããè«æ±é 19èšèŒã®æ¹æ³ã
- è«æ±é 1ã20ã®ããããäžé èšèŒã®æ¹æ³ã«ããããçæãããçå现èã
- è«æ±é 1ã20ã®ããããäžé èšèŒã®æ¹æ³ã®ããããã«ããããçæãããçå现èããã³è¬åŠçã«èš±å®¹ãããæ äœãå«ãçµæç©ã
- ïŒiïŒGSK3çµè·¯é»å®³ç©è³ªïŒïŒiiïŒ3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žïŒcAMPïŒã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ïŒããã³ïŒiiiïŒFGFçµè·¯æŽ»æ§åç©è³ªãã®å°ãªããšã2ã€ãå«ããçµæç©ã
- GSK3çµè·¯é»å®³ç©è³ªã3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ããã³FGFçµè·¯æŽ»æ§åç©è³ªãå«ããè«æ±é 23èšèŒã®çµæç©ã
- 幹现èãããã«å«ããè«æ±é 23ãŸãã¯24èšèŒã®çµæç©ã
- ïŒiïŒGSK3çµè·¯é»å®³ç©è³ªïŒïŒiiïŒ3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žïŒcAMPïŒã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ïŒããã³ïŒiiiïŒbFGFçµè·¯æŽ»æ§åç©è³ªãã®å°ãªããšã2ã€ãå«ãã现èå¹é€å¹å°ã
- GSK3çµè·¯é»å®³ç©è³ªã3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ããã³FGFçµè·¯æŽ»æ§åç©è³ªãå«ããè«æ±é 26èšèŒã®çŽ°èå¹é€å¹å°ã
- å€èœæ§å¹¹çŽ°èãããã«å«ããè«æ±é 6ãŸãã¯27èšèŒã®çŽ°èå¹é€å¹å°ã
- ïŒiïŒGSK3çµè·¯é»å®³ç©è³ªïŒïŒiiïŒ3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žïŒcAMPïŒã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ïŒããã³ïŒiiiïŒFGFçµè·¯æŽ»æ§åç©è³ªãã®å°ãªããšã2ã€ãå«ããå€èœæ§çŽ°èããéªšæ Œçåé§çŽ°èãžã®ååãèªå°ããããã®è©Šè¬ãããã
- GSK3çµè·¯é»å®³ç©è³ªã3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ããã³FGFçµè·¯æŽ»æ§åç©è³ªãå«ããè«æ±é 29èšèŒã®ãããã
- 幹现èãããã«å«ããè«æ±é 29ãŸãã¯30èšèŒã®ãããã
- 3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ã®ååšäžã§è¡æ现èãå¹é€ããå·¥çšãå«ããè¡æ现èã®å¢æ®ãå¢å ãããæ¹æ³ã
- 該ååç©ãã¢ãããªã«ã·ã¯ã©ãŒãŒã®æŽ»æ§åç©è³ªã§ãããè«æ±é 32èšèŒã®æ¹æ³ã
- 該ååç©ãããã©ã«ã¹ã³ãªã³ïŒãã©ã«ã¹ã³ãªã³èªå°äœããã³ã¢ããã°ïŒcAMPã®éå æ°Žå解æ§ã¢ããã°ïŒã€ãœãããã¬ããŒã«ïŒè¡ç®¡äœåæ§è žç®¡ããããïŒã«ã«ã·ãŠã ã€ãªããã©ã¢ïŒèè±å極ïŒcAMPãåºæ¿ãããã¯ããã¡ãŒãžç±æ¥å åïŒãã¯ããã¡ãŒãžã®æŽ»æ§åãåºæ¿ããäœçšç©è³ªïŒãã¹ããžãšã¹ãã©ãŒãŒé»å®³ç©è³ªïŒäžåäœã¢ããã«é žã·ã¯ã©ãŒãŒæŽ»æ§åããããïŒPACAPïŒïŒã³ã¬ã©æ¯çŽ ïŒããã¹ã¿ã°ã©ã³ãžã³ååç©ïŒããŒã¿2-ã¢ãã¬ããªã³å容äœã¢ãŽãã¹ãïŒããã³ãããã®ä»»æã®çµã¿åãããããªã矀ããéžæããããè«æ±é 32ãŸãã¯33èšèŒã®æ¹æ³ã
- 該ååç©ã®æ¿åºŠããçŽ0.01nMãçŽ100ÎŒMã§ãããè«æ±é 32ã34ã®ããããäžé èšèŒã®æ¹æ³ã
- æ¥è§Šãå°ãªããšã1æ¥éã§ãããè«æ±é 32ã35ã®ããããäžé èšèŒã®æ¹æ³ã
- è¡æ现èããæå·ããççµç¹ãŸãã¯çèéã®å¢å ã®åŠçœ®ãå¿ èŠãšãã察象ç±æ¥ã§ãããè«æ±é 32ã36ã®ããããäžé èšèŒã®æ¹æ³ã
- æå·ããççµç¹ãã身äœçåå·ãŸãã¯äºæ ãçŸæ£ãææãé ·äœ¿ãè¡æ¶²åŸªç°ã®åªå€±ãŸãã¯çèçž®ãããã¯çæ¶èã®çµæã§ãããè«æ±é 37èšèŒã®æ¹æ³ã
- è«æ±é 32ã38ã®ããããäžé èšèŒã®æ¹æ³ã«ããçæãããè¡æ现èã
- è«æ±é 32ã38ã®ããããäžé èšèŒã®æ¹æ³ã«ããçæãããè¡æ现èããã³è¬åŠçã«èš±å®¹ãããæ äœãå«ãè¬åŠççµæç©ã
- è«æ±é 32ã38ã®ããããäžé èšèŒã®æ¹æ³ã«ããããçæãããè¡æ现èãå«ãã察象ã«è¡æ现èã移æ€ããããã®è¬åŠççµæç©ã
- è«æ±é 1ã20ã®ããããäžé èšèŒã®æ¹æ³ã«ããããçæãããçå现èãå«ãã察象ã«çå现èã移æ€ããããã®è¬åŠççµæç©ã
- 察象ããæå·ããççµç¹ãŸãã¯çèéã®å¢å ã®åŠçœ®ãå¿ èŠãšããŠãããè«æ±é 41ãŸãã¯42èšèŒã®è¬åŠççµæç©ã
- ïŒiïŒGSK3çµè·¯é»å®³ç©è³ªïŒïŒiiïŒ3',5'-ç°ç¶ã¢ããã·ã³äžãªã³é žïŒcAMPïŒã®çŽ°èå ã¬ãã«ãå¢å ãããååç©ïŒããã³ïŒiiiïŒFGFçµè·¯æŽ»æ§åç©è³ªãã®å°ãªããšã2ã€ã®çµã¿åãããå«ããæå·ããççµç¹ãŸãã¯çèéã®å¢å ã®ããã«å¯Ÿè±¡ãåŠçœ®ããããã®è¬åŠççµæç©ã
- ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã§ãã£ãŠãè©Šéšååç©ã®ååšäžã§å²çãå¹é€ããå·¥çšã§ãã£ãŠãå²çãã¬ããŒã¿ãŒéºäŒåãå«ã¿ãã¬ããŒã¿ãŒéºäŒåã现èç³»èç¹ç°çããŒã«ãŒãã³ãŒãããŠãããã€çºçŸããããšãã«æ€åºå¯èœãªã·ã°ãã«ãçæãããå·¥çšïŒããã³æ€åºå¯èœãªã·ã°ãã«ã枬å®ïŒæ€åºããå·¥çšã§ãã£ãŠãæ€åºå¯èœãªã·ã°ãã«ã®ã¬ãã«ãŸãã¯éã®å€åããè©Šéšååç©ã现èç³»èç¹ç°çããŒã«ãŒãçºçŸãã现èç³»èã®çºçãŸãã¯æ©èœã調æŽããããšã瀺ããå·¥çšããå«ããã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
- ã¬ããŒã¿ãŒéºäŒåããèå ã¿ã³ãã¯è³ªã«èåããã现èç³»èç¹ç°çããŒã«ãŒãå«ãèåã¿ã³ãã¯è³ªãã³ãŒããããè«æ±é 45èšèŒã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
- å²çã2ã€ã®ç°ãªãã¬ããŒã¿ãŒéºäŒåãå«ã¿ãåã¬ããŒã¿ãŒéºäŒåãç°ãªã现èç³»èç¹ç°çããŒã«ãŒãã³ãŒãããŠãããã€çºçŸããããšãã«æ€åºå¯èœãªã·ã°ãã«ãçæãããè«æ±é 45ãŸãã¯46èšèŒã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
- å²çãããŒãã©ãã£ãã·ã¥ã®å²çã§ãããè«æ±é 45ã47ã®ããããäžé èšèŒã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
- è©Šéšååç©ããææ©ãŸãã¯ç¡æ©äœååïŒãµãã«ãªã³ïŒãªãªãŽç³ïŒå€ç³ïŒããããïŒã¿ã³ãã¯è³ªïŒããããã¢ããã°ããã³èªå°äœïŒããããæš¡å£äœïŒæ žé žïŒæ žé žã¢ããã°ããã³èªå°äœïŒçç©ææããåŸãããæœåºç©ïŒåç©çµç¹ïŒå€©ç¶ã«ååšãããŸãã¯åææ§ã®çµæç©ïŒãªãã³ã«ãããã®ä»»æã®çµã¿åãããããªã矀ããéžæããããè«æ±é 45ã48ã®ããããäžé èšèŒã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
- è©Šéšååç©ãã0.01nmãçŽ10mMã®æçµæ¿åºŠã§ã€ã³ãã¥ããŒãããããè«æ±é 45ã49ã®ããããäžé èšèŒã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
- é«ã¹ã«ãŒãããã¹ã¯ãªãŒãã³ã°ïŒHTSïŒã¢ãã»ã€ã§ãããè«æ±é 45ã50ã®ããããäžé èšèŒã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã
- è«æ±é 45ã51ã®ããããäžé èšèŒã®ã¹ã¯ãªãŒãã³ã°ã¢ãã»ã€ã«ãã£ãŠéžæãããååç©ã
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261610668P | 2012-03-14 | 2012-03-14 | |
US61/610,668 | 2012-03-14 | ||
US201261720713P | 2012-10-31 | 2012-10-31 | |
US61/720,713 | 2012-10-31 | ||
PCT/US2013/031504 WO2013138623A1 (en) | 2012-03-14 | 2013-03-14 | High-throughput image-based chemical screening in zebrafish blastomere cell culture |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2015513896A JP2015513896A (ja) | 2015-05-18 |
JP2015513896A5 true JP2015513896A5 (ja) | 2016-05-12 |
JP6445422B2 JP6445422B2 (ja) | 2018-12-26 |
Family
ID=49161817
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015500623A Expired - Fee Related JP6445422B2 (ja) | 2012-03-14 | 2013-03-14 | ãŒãã©ãã£ãã·ã¥å²ç现èå¹é€ç©ã«ãããé«ã¹ã«ãŒãããç»åããŒã¹ååŠã¹ã¯ãªãŒãã³ã° |
Country Status (4)
Country | Link |
---|---|
US (2) | US9771560B2 (ja) |
EP (1) | EP2825637A4 (ja) |
JP (1) | JP6445422B2 (ja) |
WO (1) | WO2013138623A1 (ja) |
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB201212960D0 (en) * | 2012-07-20 | 2012-09-05 | Common Services Agency | Erythroid production |
US9566310B2 (en) | 2012-09-10 | 2017-02-14 | Board Of Regents Of The Nevada System Of Higher Education On Behalf Of The University Of Nevada, Reno | Methods of treating muscular dystrophy |
US9707210B2 (en) | 2013-03-15 | 2017-07-18 | Board Of Regents Of The Nevada System Of Higher Education On Behalf Of The University Of Nevada, Reno | Methods of treating muscular dystrophy |
CN107709545A (zh) * | 2015-04-22 | 2018-02-16 | å纳ç¥è¯äº§ææ§è¡ç§äººæéå ¬åž | ä»å¹²ç»èçæèè谱系ç»è |
WO2017027984A1 (en) * | 2015-08-20 | 2017-02-23 | Simon Fraser University | Compounds and methods for treatment of cancer by inhibiting atg4b and blocking autophagy |
CN105238742B (zh) * | 2015-11-19 | 2019-11-08 | æ¹ååžèå€§åŠ | æ马鱌诱富æ§å€èœå¹²ç»èç诱富æ¹æ³ä»¥åçšäºè¯¥è¯±å¯Œæ¹æ³ç诱富åå¹å »åºãiPSå¹å »åº |
US11318167B2 (en) | 2015-12-11 | 2022-05-03 | The Johns Hopkins University | Isolation of fusion-competent myoblasts and therapeutic applications thereof related to muscular dystrophy |
JP7090544B2 (ja) * | 2016-04-27 | 2022-06-24 | æŠç°è¬åå·¥æ¥æ ªåŒäŒç€Ÿ | éªšæ Œçåé§çŽ°èåã³éªšæ Œç现èã®è£œé æ¹æ³ |
EP3532605A4 (en) | 2016-10-26 | 2021-01-13 | Sonic Master Limited | ENHANCED GENERATION OF MUSCLE LINE CELLS AND THEIR THERAPEUTIC USES |
WO2019118768A1 (en) * | 2017-12-13 | 2019-06-20 | Rita Perlingeiro | Enhanced differentiation and maturation of pluripotent stem cell-derived myogenic cells |
CN110859854A (zh) * | 2018-08-08 | 2020-03-06 | äžæµ·åžäžæ¹å»é¢ | æ²»çç¥ç»æºæ§èèè猩çè¯ç©ç»åç©åå ¶å¶æ³ååºçš |
US20220041990A1 (en) * | 2019-04-03 | 2022-02-10 | The Johns Hopkins University | Methods, compositions, and kits for producing skeletal muscle stem cells and treating disorders |
CN110305837A (zh) * | 2019-06-05 | 2019-10-08 | 西ååžèå€§åŠ | ç£·é žäºé ¯é ¶5掻æ§æå¶åäœäžºè¯±å¯Œæ马鱌åµæ¯ç»èæççå¬çåçåºçš |
CN111411080B (zh) * | 2020-03-19 | 2022-08-09 | åäº¬å€§åŠ | äžç§å犻åå¹å »æ马鱌å代è å·šå¬ç»èçæ¹æ³ |
CN111760026A (zh) * | 2020-08-06 | 2020-10-13 | æ±ªç¬ | FGFR2bæå¶åååšå¶å€æ²»çPAFä»å¯ŒççŸç è¯ç©äžçåºçš |
KR102300616B1 (ko) * | 2021-02-05 | 2021-09-08 | ììžëíêµì°ííë ¥ëš | ê°ìŒ êŽë š ì§ë³ 몚ëž, ìŽì ì ì¡°ë°©ë², ë° ë©Žìíì±ë¬Œì§ì ì€í¬ëŠ¬ë ë°©ë² |
JP2023082935A (ja) * | 2021-12-03 | 2023-06-15 | åœç«å€§åŠæ³äººä¹å·å€§åŠ | éé¡ã®çæ®å¹¹çŽ°èã®å¹é€æ¹æ³ |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1385938A1 (en) * | 2001-04-23 | 2004-02-04 | Nsgene A/S | Method and culture medium for producing neural cells expressing tyrosine hydroxylase |
WO2008060792A2 (en) | 2006-10-12 | 2008-05-22 | Stem Cells Innovations | Novel cells, compositions, and methods |
RU2010139426A (ru) * | 2008-03-17 | 2012-04-27 | Ðе СкÑÐžÐ¿Ñ Ð ÐµÑÐµÑ ÐÐœÑÑОÑÑÑÑ (Us) | ÐПЌбОМаÑÐžÑ Ñ ÐžÐŒÐžÑеÑкПгП О геМеÑОÑеÑкПгП Ð¿ÐŸÐŽÑ ÐŸÐŽÐŸÐ² к пПлÑÑÐµÐœÐžÑ ÐžÐœÐŽÑÑОÑПваММÑÑ Ð¿Ð»ÑÑОпПÑеМÑÐœÑÑ ÑÑвПлПвÑÑ ÐºÐ»ÐµÑПк |
-
2013
- 2013-03-14 JP JP2015500623A patent/JP6445422B2/ja not_active Expired - Fee Related
- 2013-03-14 EP EP13761095.2A patent/EP2825637A4/en not_active Withdrawn
- 2013-03-14 US US14/384,514 patent/US9771560B2/en active Active
- 2013-03-14 WO PCT/US2013/031504 patent/WO2013138623A1/en active Application Filing
-
2017
- 2017-08-23 US US15/684,617 patent/US20180112182A1/en not_active Abandoned
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2015513896A5 (ja) | ||
JP6445422B2 (ja) | ãŒãã©ãã£ãã·ã¥å²ç现èå¹é€ç©ã«ãããé«ã¹ã«ãŒãããç»åããŒã¹ååŠã¹ã¯ãªãŒãã³ã° | |
WO2017160234A1 (en) | Generation of midbrain-specific organoids from human pluripotent stem cells | |
Senthil et al. | Vascular endothelial growth factor induces protein synthesis in renal epithelial cells: a potential role in diabetic nephropathy | |
Peltier et al. | PI3K/Akt and CREB regulate adult neural hippocampal progenitor proliferation and differentiation | |
Kardon et al. | Local extrinsic signals determine muscle and endothelial cell fate and patterning in the vertebrate limb | |
MX2012007026A (es) | Compuestos que promueven la replicacion de celula beta y metodos de su uso. | |
US20160082015A1 (en) | Methods, compositions and kits for promoting motor neuron survival and treating and diagnosing neurodegenerative disorders | |
Persaud et al. | Tyrosine kinases play a permissive role in glucose-induced insulin secretion from adult rat islets | |
CN1840181A (zh) | éæ©æ§pde10æå¶ç©çæ²»ççšé | |
Song et al. | Specific differentiation of mesenchymal stem cells by small molecules | |
Sharifpanah et al. | Mechanical strain stimulates vasculogenesis and expression of angiogenesis guidance molecules of embryonic stem cells through elevation of intracellular calcium, reactive oxygen species and nitric oxide generation | |
Ding et al. | Small molecules and future regenerative medicine | |
WO2016137400A1 (en) | Methods and compositions for expansion and differentiation of skeletal muscle stem cells or progenitor cells | |
Khan et al. | Participation of cAMP-dependent protein kinase and MAP kinase pathways during Anabas testudineus oocyte maturation | |
CN107429233B (zh) | ç¥ç»ç³»ç»ç»èçå¶é æ¹æ³ | |
CN102297931B (zh) | åºäºå·å¢šæå°åççæççŽ æä»·æµå®æ¹æ³ | |
Iqbal et al. | Regulation of basal and norepinephrine-induced cAMP and ICa in hiPSC-cardiomyocytes: effects of culture conditions and comparison to adult human atrial cardiomyocytes | |
Peng et al. | From the camp pathway to search the ketamine-related learning and memory | |
Gutierrez et al. | Adenylate cyclase of osteoblast-like cells from rat osteosarcoma is stimulated by calcitonin as well as parathyroid hormone | |
Cossu et al. | Reduced acetylcholine sensitivity in dystrophic mouse myotubes in vitro | |
JP2023520466A (ja) | äžè³ããŒããã³ãã¥ãŒãã³ã®çææ¹æ³ãäžè³ãã¥ãŒãã³ããã³ãã®äœ¿çš | |
Lagord et al. | Satellite cell myogenesis is highly stimulated by the kinase inhibitor iso-H7: comparison with HA1004 and staurosporine effects | |
US20220333071A1 (en) | Methods of making, expanding and purifying midbrain dopaminergic progenitor cells | |
Yan et al. | Enhanced proliferation and neuronal differentiation of neural stem cell with vertically surface microenvironment |