DE102010007281A1 - Neue Aminoalkyl-oxazol- und Aminoalkyl-thiazolcarbonsäureamide und ihre Anwendung zur Stimulation der endogenen situ Regeneration von Haarsinneszellen im Corti'schen Organ des Innenohres beim Säuger - Google Patents
Neue Aminoalkyl-oxazol- und Aminoalkyl-thiazolcarbonsäureamide und ihre Anwendung zur Stimulation der endogenen situ Regeneration von Haarsinneszellen im Corti'schen Organ des Innenohres beim Säuger Download PDFInfo
- Publication number
- DE102010007281A1 DE102010007281A1 DE102010007281A DE102010007281A DE102010007281A1 DE 102010007281 A1 DE102010007281 A1 DE 102010007281A1 DE 102010007281 A DE102010007281 A DE 102010007281A DE 102010007281 A DE102010007281 A DE 102010007281A DE 102010007281 A1 DE102010007281 A1 DE 102010007281A1
- Authority
- DE
- Germany
- Prior art keywords
- cells
- regeneration
- aminoalkyl
- organ
- compounds
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 210000002768 hair cell Anatomy 0.000 title claims abstract description 57
- 230000008929 regeneration Effects 0.000 title claims abstract description 56
- 238000011069 regeneration method Methods 0.000 title claims abstract description 56
- 210000002985 organ of corti Anatomy 0.000 title claims abstract description 35
- 241000124008 Mammalia Species 0.000 title claims abstract description 21
- 210000001835 viscera Anatomy 0.000 title 1
- 210000004027 cell Anatomy 0.000 claims abstract description 102
- 150000001875 compounds Chemical class 0.000 claims abstract description 84
- 210000000056 organ Anatomy 0.000 claims abstract description 42
- 210000003027 ear inner Anatomy 0.000 claims abstract description 39
- 230000035755 proliferation Effects 0.000 claims abstract description 21
- 230000032459 dedifferentiation Effects 0.000 claims abstract description 20
- 238000002360 preparation method Methods 0.000 claims abstract description 20
- 206010011878 Deafness Diseases 0.000 claims abstract description 18
- 208000016354 hearing loss disease Diseases 0.000 claims abstract description 17
- 239000000825 pharmaceutical preparation Substances 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 16
- 230000001172 regenerating effect Effects 0.000 claims abstract description 16
- 230000001953 sensory effect Effects 0.000 claims abstract description 16
- 230000008093 supporting effect Effects 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 12
- 239000000203 mixture Substances 0.000 claims abstract description 12
- 238000011065 in-situ storage Methods 0.000 claims abstract description 11
- 230000001364 causal effect Effects 0.000 claims abstract description 9
- 238000009472 formulation Methods 0.000 claims abstract description 6
- 230000008569 process Effects 0.000 claims abstract description 5
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 3
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 3
- 238000004519 manufacturing process Methods 0.000 claims abstract 3
- 239000000243 solution Substances 0.000 claims description 37
- 210000001519 tissue Anatomy 0.000 claims description 30
- 150000001413 amino acids Chemical class 0.000 claims description 18
- 230000006378 damage Effects 0.000 claims description 16
- 210000003477 cochlea Anatomy 0.000 claims description 15
- ALEXXDVDDISNDU-JZYPGELDSA-N cortisol 21-acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O ALEXXDVDDISNDU-JZYPGELDSA-N 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 14
- 239000000651 prodrug Substances 0.000 claims description 12
- 229940002612 prodrug Drugs 0.000 claims description 12
- 231100000888 hearing loss Toxicity 0.000 claims description 11
- 230000010370 hearing loss Effects 0.000 claims description 11
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 10
- -1 (1H-indol-3-yl) -ethyl Chemical group 0.000 claims description 9
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 8
- 239000000725 suspension Substances 0.000 claims description 8
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 238000007363 ring formation reaction Methods 0.000 claims description 6
- 210000004556 brain Anatomy 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 210000002216 heart Anatomy 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 230000004071 biological effect Effects 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 210000002027 skeletal muscle Anatomy 0.000 claims description 4
- 230000009435 amidation Effects 0.000 claims description 3
- 238000007112 amidation reaction Methods 0.000 claims description 3
- 239000000499 gel Substances 0.000 claims description 3
- 239000007790 solid phase Substances 0.000 claims description 3
- 230000009471 action Effects 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 2
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004350 aryl cycloalkyl group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 239000006071 cream Substances 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000004367 cycloalkylaryl group Chemical group 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 239000003599 detergent Substances 0.000 claims description 2
- 210000000959 ear middle Anatomy 0.000 claims description 2
- 239000000839 emulsion Substances 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 239000000017 hydrogel Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 239000006210 lotion Substances 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 239000006072 paste Substances 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 239000004615 ingredient Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000009885 systemic effect Effects 0.000 claims 1
- 229910052727 yttrium Inorganic materials 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 23
- 230000032823 cell division Effects 0.000 abstract description 19
- 230000000694 effects Effects 0.000 abstract description 17
- 239000000126 substance Substances 0.000 abstract description 17
- 150000003384 small molecules Chemical class 0.000 abstract description 10
- 230000006698 induction Effects 0.000 abstract description 7
- 239000013543 active substance Substances 0.000 abstract description 5
- 231100000895 deafness Toxicity 0.000 abstract description 5
- 238000001415 gene therapy Methods 0.000 abstract description 4
- 231100000199 ototoxic Toxicity 0.000 abstract description 4
- 230000002970 ototoxic effect Effects 0.000 abstract description 4
- 230000002068 genetic effect Effects 0.000 abstract description 3
- 230000006727 cell loss Effects 0.000 abstract description 2
- 238000011476 stem cell transplantation Methods 0.000 abstract description 2
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- 230000003660 hair regeneration Effects 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 37
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 37
- 229950004398 broxuridine Drugs 0.000 description 37
- 210000000130 stem cell Anatomy 0.000 description 29
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 238000003786 synthesis reaction Methods 0.000 description 20
- YBBNZJWYHZSZEE-UHFFFAOYSA-N 2-[1-amino-2-(1h-indol-3-yl)ethyl]-n-cyclohexyl-1,3-oxazole-4-carboxamide Chemical compound C=1NC2=CC=CC=C2C=1CC(N)C(OC=1)=NC=1C(=O)NC1CCCCC1 YBBNZJWYHZSZEE-UHFFFAOYSA-N 0.000 description 19
- 238000001727 in vivo Methods 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 229920005989 resin Polymers 0.000 description 17
- 239000011347 resin Substances 0.000 description 17
- 238000000338 in vitro Methods 0.000 description 16
- 101100247004 Rattus norvegicus Qsox1 gene Proteins 0.000 description 13
- 238000004113 cell culture Methods 0.000 description 12
- 230000000875 corresponding effect Effects 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- 238000010348 incorporation Methods 0.000 description 11
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 230000001413 cellular effect Effects 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 210000000981 epithelium Anatomy 0.000 description 8
- 210000004940 nucleus Anatomy 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 239000012043 crude product Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 150000003557 thiazoles Chemical class 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 241000271566 Aves Species 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000022131 cell cycle Effects 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 230000004069 differentiation Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 208000014674 injury Diseases 0.000 description 5
- 210000000067 inner hair cell Anatomy 0.000 description 5
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 5
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 150000003556 thioamides Chemical class 0.000 description 5
- 102000000905 Cadherin Human genes 0.000 description 4
- 108050007957 Cadherin Proteins 0.000 description 4
- 241000700199 Cavia porcellus Species 0.000 description 4
- 206010011903 Deafness traumatic Diseases 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 208000002946 Noise-Induced Hearing Loss Diseases 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 102100031834 Unconventional myosin-VI Human genes 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 230000011278 mitosis Effects 0.000 description 4
- 108010049787 myosin VI Proteins 0.000 description 4
- 230000005868 ontogenesis Effects 0.000 description 4
- 150000002916 oxazoles Chemical class 0.000 description 4
- 210000001778 pluripotent stem cell Anatomy 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 230000002269 spontaneous effect Effects 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- JLSKPBDKNIXMBS-SECBINFHSA-N (2r)-2-amino-3-(1h-indol-3-yl)propanamide Chemical compound C1=CC=C2C(C[C@@H](N)C(N)=O)=CNC2=C1 JLSKPBDKNIXMBS-SECBINFHSA-N 0.000 description 3
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 206010011891 Deafness neurosensory Diseases 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 229930193140 Neomycin Natural products 0.000 description 3
- 208000009966 Sensorineural Hearing Loss Diseases 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 229940126575 aminoglycoside Drugs 0.000 description 3
- 239000002771 cell marker Substances 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 210000001671 embryonic stem cell Anatomy 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000002427 irreversible effect Effects 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 229960004927 neomycin Drugs 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 231100000879 sensorineural hearing loss Toxicity 0.000 description 3
- 208000023573 sensorineural hearing loss disease Diseases 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 230000008733 trauma Effects 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- NFVNYBJCJGKVQK-CYBMUJFWSA-N (2r)-3-(1h-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound C1=CC=C2C(C[C@@H](NC(=O)OC(C)(C)C)C(O)=O)=CNC2=C1 NFVNYBJCJGKVQK-CYBMUJFWSA-N 0.000 description 2
- QEDVGROSOZBGOZ-WXXKFALUSA-N (e)-but-2-enedioic acid;n-[2-[[2-hydroxy-3-(4-hydroxyphenoxy)propyl]amino]ethyl]morpholine-4-carboxamide Chemical compound OC(=O)\C=C\C(O)=O.C=1C=C(O)C=CC=1OCC(O)CNCCNC(=O)N1CCOCC1.C=1C=C(O)C=CC=1OCC(O)CNCCNC(=O)N1CCOCC1 QEDVGROSOZBGOZ-WXXKFALUSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
- 241001136792 Alle Species 0.000 description 2
- 102000016843 Calbindin 2 Human genes 0.000 description 2
- 108010028326 Calbindin 2 Proteins 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 2
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 2
- 101000701142 Homo sapiens Transcription factor ATOH1 Proteins 0.000 description 2
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 2
- 101150113031 Jag1 gene Proteins 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 102000008730 Nestin Human genes 0.000 description 2
- 108010088225 Nestin Proteins 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 230000018199 S phase Effects 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 102000013275 Somatomedins Human genes 0.000 description 2
- 102100031835 Unconventional myosin-VIIa Human genes 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 229960004821 amikacin Drugs 0.000 description 2
- LKCWBDHBTVXHDL-RMDFUYIESA-N amikacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)[C@@H](O)[C@H](O)[C@H]1O LKCWBDHBTVXHDL-RMDFUYIESA-N 0.000 description 2
- 229940126574 aminoglycoside antibiotic Drugs 0.000 description 2
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 210000003855 cell nucleus Anatomy 0.000 description 2
- 238000011097 chromatography purification Methods 0.000 description 2
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 2
- 230000013020 embryo development Effects 0.000 description 2
- VICYTAYPKBLQFB-UHFFFAOYSA-N ethyl 3-bromo-2-oxopropanoate Chemical compound CCOC(=O)C(=O)CBr VICYTAYPKBLQFB-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 229940126864 fibroblast growth factor Drugs 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- IYWCBYFJFZCCGV-UHFFFAOYSA-N formamide;hydrate Chemical compound O.NC=O IYWCBYFJFZCCGV-UHFFFAOYSA-N 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 210000002266 hair cells auditory Anatomy 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 238000012606 in vitro cell culture Methods 0.000 description 2
- 210000001445 inner phalangeal cell Anatomy 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 230000000366 juvenile effect Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 210000005055 nestin Anatomy 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 229920005990 polystyrene resin Polymers 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000008672 reprogramming Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 210000001079 scala tympani Anatomy 0.000 description 2
- 238000007423 screening assay Methods 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000004114 suspension culture Methods 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- 230000001720 vestibular Effects 0.000 description 2
- BUHVIAUBTBOHAG-FOYDDCNASA-N (2r,3r,4s,5r)-2-[6-[[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound COC1=CC(OC)=CC(C(CNC=2C=3N=CN(C=3N=CN=2)[C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)C=2C(=CC=CC=2)C)=C1 BUHVIAUBTBOHAG-FOYDDCNASA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- JTNCEQNHURODLX-UHFFFAOYSA-N 2-phenylethanimidamide Chemical compound NC(=N)CC1=CC=CC=C1 JTNCEQNHURODLX-UHFFFAOYSA-N 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- 101150002428 Atoh1 gene Proteins 0.000 description 1
- ILQRZOSTDQQPMP-IBGZPJMESA-N CC(N[C@@H](Cc1c[nH]c2c1cccc2)c1nc(C(NC2CCCCC2)=O)c[o]1)=O Chemical compound CC(N[C@@H](Cc1c[nH]c2c1cccc2)c1nc(C(NC2CCCCC2)=O)c[o]1)=O ILQRZOSTDQQPMP-IBGZPJMESA-N 0.000 description 1
- 0 CC=*NC(*)C1OC1N Chemical compound CC=*NC(*)C1OC1N 0.000 description 1
- LDPXTOKSXQNYGE-HQVZTVAUSA-N CCC(C)[C@@H](c1nc(C(NC2CCCCC2)=O)c[o]1)N Chemical compound CCC(C)[C@@H](c1nc(C(NC2CCCCC2)=O)c[o]1)N LDPXTOKSXQNYGE-HQVZTVAUSA-N 0.000 description 1
- NTEUDULMGZYHKU-HNNXBMFYSA-N CSCC[C@@H](c1nc(C(Nc(cc2)ccc2N2CCOCC2)=O)c[o]1)N Chemical compound CSCC[C@@H](c1nc(C(Nc(cc2)ccc2N2CCOCC2)=O)c[o]1)N NTEUDULMGZYHKU-HNNXBMFYSA-N 0.000 description 1
- ZYBYRAGBXBMDDL-HNNXBMFYSA-N CSCC[C@@H](c1nc(C(Nc(cc2)ccc2N2CCOCC2)=O)c[s]1)N Chemical compound CSCC[C@@H](c1nc(C(Nc(cc2)ccc2N2CCOCC2)=O)c[s]1)N ZYBYRAGBXBMDDL-HNNXBMFYSA-N 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 241000288029 Coturnix Species 0.000 description 1
- 206010063602 Exposure to noise Diseases 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 241000699694 Gerbillinae Species 0.000 description 1
- 102100039289 Glial fibrillary acidic protein Human genes 0.000 description 1
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 208000032041 Hearing impaired Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010048865 Hypoacusis Diseases 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- JLSKPBDKNIXMBS-VIFPVBQESA-N L-tryptophanamide Chemical compound C1=CC=C2C(C[C@H](N)C(N)=O)=CNC2=C1 JLSKPBDKNIXMBS-VIFPVBQESA-N 0.000 description 1
- 241000272168 Laridae Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- YBBNZJWYHZSZEE-INIZCTEOSA-N N[C@@H](Cc1c[nH]c2c1cccc2)c1nc(C(NC2CCCCC2)=O)c[o]1 Chemical compound N[C@@H](Cc1c[nH]c2c1cccc2)c1nc(C(NC2CCCCC2)=O)c[o]1 YBBNZJWYHZSZEE-INIZCTEOSA-N 0.000 description 1
- ARZCGNZKCDCQRK-UHFFFAOYSA-N O=C(c1c[s]c(C2CNCCC2)n1)NC1CCCCC1 Chemical compound O=C(c1c[s]c(C2CNCCC2)n1)NC1CCCCC1 ARZCGNZKCDCQRK-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 206010033109 Ototoxicity Diseases 0.000 description 1
- 208000020764 Sensation disease Diseases 0.000 description 1
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical class O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
- 102000009618 Transforming Growth Factors Human genes 0.000 description 1
- 108010009583 Transforming Growth Factors Proteins 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 238000004115 adherent culture Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 210000003030 auditory receptor cell Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000007321 biological mechanism Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 150000004651 carbonic acid esters Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000008668 cellular reprogramming Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000010428 chromatin condensation Effects 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000001609 comparable effect Effects 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 210000000243 deiters cell Anatomy 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- ZINJLDJMHCUBIP-UHFFFAOYSA-N ethametsulfuron-methyl Chemical compound CCOC1=NC(NC)=NC(NC(=O)NS(=O)(=O)C=2C(=CC=CC=2)C(=O)OC)=N1 ZINJLDJMHCUBIP-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000013160 medical therapy Methods 0.000 description 1
- 239000012528 membrane Substances 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
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 210000001178 neural stem cell Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000012758 nuclear staining Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 231100000262 ototoxicity Toxicity 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 210000004049 perilymph Anatomy 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 210000000697 sensory organ Anatomy 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000008939 stimulatory process Effects 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000007279 water homeostasis Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- A61P27/00—Drugs for disorders of the senses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Neurology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Medicinal Preparation (AREA)
Priority Applications (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102010007281A DE102010007281A1 (de) | 2010-02-08 | 2010-02-08 | Neue Aminoalkyl-oxazol- und Aminoalkyl-thiazolcarbonsäureamide und ihre Anwendung zur Stimulation der endogenen situ Regeneration von Haarsinneszellen im Corti'schen Organ des Innenohres beim Säuger |
| EP11703394A EP2534139A1 (de) | 2010-02-08 | 2011-02-04 | Neue aminoalkyl-oxazol- und aminoalkyl-thiazolcarbonsäureamide als regenerationsfördernde substanzen für sinnesorgane und postmitotische gewebe |
| CA2789013A CA2789013A1 (en) | 2010-02-08 | 2011-02-04 | Novel aminoalkyloxazole- and aminoalkylthiazolecarboxylic acid amides as regeneration-promoting substances for sensory organs and post-mitotic tissue |
| PCT/EP2011/000502 WO2011095338A1 (de) | 2010-02-08 | 2011-02-04 | Neue aminoalkyl-oxazol- und aminoalkyl-thiazolcarbonsäureamide als regenerationsfördernde substanzen für sinnesorgane und postmitotische gewebe |
| US13/577,503 US20130012514A1 (en) | 2010-02-08 | 2011-02-04 | Aminoalkyloxazole and aminoalkylthiazolecarboxylic acid amides as regeneration-promoting substances for sensory organs and post-mitotic tissue |
| CN201180017156.5A CN102947281B (zh) | 2010-02-08 | 2011-02-04 | 作为感觉器官和有丝分裂后组织的再生促进物质的新颖的氨基烷基噁唑甲酰胺和氨基烷基噻唑甲酰胺 |
| JP2012552297A JP2013518917A (ja) | 2010-02-08 | 2011-02-04 | 感覚器官及び有糸分裂後組織のための再生促進物質としての新規なアミノアルキルオキサゾール及びアミノアルキルチアゾールカルボン酸アミド |
| US14/208,419 US8889723B2 (en) | 2010-02-08 | 2014-03-13 | Aminoalkyloxazole and aminoalkylthiazolecarboxylic acid amides as regeneration-promoting substances for sensory organs and post-mitotic tissues |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102010007281A DE102010007281A1 (de) | 2010-02-08 | 2010-02-08 | Neue Aminoalkyl-oxazol- und Aminoalkyl-thiazolcarbonsäureamide und ihre Anwendung zur Stimulation der endogenen situ Regeneration von Haarsinneszellen im Corti'schen Organ des Innenohres beim Säuger |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE102010007281A1 true DE102010007281A1 (de) | 2011-08-11 |
Family
ID=43754901
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE102010007281A Withdrawn DE102010007281A1 (de) | 2010-02-08 | 2010-02-08 | Neue Aminoalkyl-oxazol- und Aminoalkyl-thiazolcarbonsäureamide und ihre Anwendung zur Stimulation der endogenen situ Regeneration von Haarsinneszellen im Corti'schen Organ des Innenohres beim Säuger |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US20130012514A1 (https=) |
| EP (1) | EP2534139A1 (https=) |
| JP (1) | JP2013518917A (https=) |
| CN (1) | CN102947281B (https=) |
| CA (1) | CA2789013A1 (https=) |
| DE (1) | DE102010007281A1 (https=) |
| WO (1) | WO2011095338A1 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3366683A1 (en) * | 2017-02-28 | 2018-08-29 | Acousia Therapeutics GmbH | Cyclic amides, acteamides and ureas useful as potassium channel openers |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2871181B1 (en) | 2013-11-12 | 2016-10-05 | Acousia Therapeutics GmbH | Novel Compounds for Regeneration of Terminally-Differentiated Cells and tissues |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999042088A2 (de) | 1998-02-23 | 1999-08-26 | Otogene Aktiengesellschaft | Verfahren zur behandlung von erkrankungen oder störungen des innenohrs |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5378803A (en) * | 1987-12-11 | 1995-01-03 | Sterling Winthrop Inc. | Azole-fused peptides and processes for preparation thereof |
| EP1126855B1 (en) * | 1998-09-25 | 2007-05-09 | Cephalon, Inc. | Use of fused pyrrolocarbazoles for preventing/treating damage to sensory hair cells and cochlear neurons |
| TW502019B (en) * | 1999-03-26 | 2002-09-11 | Cocensys Inc | Aryl substituted pyrazoles, imidazoles, oxazoles, thiazoles and pyrroles, and the use thereof |
| CN1441841B (zh) * | 2000-07-11 | 2013-03-20 | 桑得医药品公司 | 对内耳的细胞再生和分化的刺激 |
| UA89035C2 (ru) * | 2003-12-03 | 2009-12-25 | Лео Фарма А/С | Эфиры гидроксамовых кислот и их фармацевтическое применение |
| JP2008502595A (ja) * | 2004-03-31 | 2008-01-31 | エグゼリクシス, インコーポレイテッド | 未分化リンパ腫キナーゼモジュレータおよびその使用方法 |
| JP5182088B2 (ja) * | 2006-04-19 | 2013-04-10 | アステラス製薬株式会社 | アゾールカルボキサミド誘導体 |
| GB0614538D0 (en) * | 2006-07-21 | 2006-08-30 | Univ Cambridge Tech | Therapeutic Compounds And Their Use |
-
2010
- 2010-02-08 DE DE102010007281A patent/DE102010007281A1/de not_active Withdrawn
-
2011
- 2011-02-04 US US13/577,503 patent/US20130012514A1/en not_active Abandoned
- 2011-02-04 CN CN201180017156.5A patent/CN102947281B/zh not_active Expired - Fee Related
- 2011-02-04 WO PCT/EP2011/000502 patent/WO2011095338A1/de not_active Ceased
- 2011-02-04 JP JP2012552297A patent/JP2013518917A/ja active Pending
- 2011-02-04 EP EP11703394A patent/EP2534139A1/de not_active Withdrawn
- 2011-02-04 CA CA2789013A patent/CA2789013A1/en not_active Abandoned
-
2014
- 2014-03-13 US US14/208,419 patent/US8889723B2/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999042088A2 (de) | 1998-02-23 | 1999-08-26 | Otogene Aktiengesellschaft | Verfahren zur behandlung von erkrankungen oder störungen des innenohrs |
Non-Patent Citations (44)
| Title |
|---|
| Chen S, Zhang Q, Wu X, Schultz PG, Ding S (2004) Dedifferentiation of lineage-committed cells by a small molecule. J Am Chem Soc 126(2): 410-411 |
| Corwin JT, Cotanche DA (1988) Regeneration of sensory hair cells after acoustic trauma. Science 240: 1772-1774 |
| Cotanche DA (1987) Regeneration of hair cell stereocilia bundles in the chick cochlea following severe acoustic trauma. Hear Res 30: 181-196 |
| Cotanche DA (1999) Structural recovery from sound and aminoglycoside damage in the avian cochlea. Audiol Neurootol 4: 271-285 |
| Cruz RM, Lambert PM, Rubel EW (1987) Light microscopic evidence of hair cell regeneration after gentamicin toxicity in chick cochlea. Arch Otolaryngol Head Neck Surg 113: 1058-1062 |
| Daudet N, Ripoll C, Lenoir M (2002) Transforming growth factor induced cellular changes in organotypic cultures of juvenile, amikacin-treated rat organ of Corti. J Comp Neurol 442: 6-22 |
| Daudet N, Vago P, Ripoll C, Humbert G, Pujol R, Lenoir M (1998) Characterization of atypical cells in the juvenil rat organ of Corti after aminoglycoside ototoxicity. J Comp Neurol 401: 145-162 |
| Feng B, Ng JH, Heng JC, Ng HH (2009) Molecules that promote or enhance reprogramming of somatic cells to induced pluripotent stem cells. Cell Stem Cell 4(4): 301-312 |
| Hahn H, Müller M, Löwenheim H (2008) Whole organ culture of the postnatal sensory inner ear in simulated microgravity. J Neurosci Meth (in Druck) |
| ifo-Institut für Wirtschaftsforschung in Zusammenarbeit mit Infratest Gesundheitsforschung im Auftrag des Deutschen Grünen Kreuzes, Marburg "Hörtest 1985", Sektion "Gutes Hören" (1986) |
| Izumikawa M, Minoda R, Kawamoto K, Abrashkin KA, Swiderski DL, Dolan DF, Brough DE, Raphael Y (2005) Auditory hair cell replacement and hearing improvement by Atoh1 gene therapy in deaf mammals. Nat Med 11: 271-276 |
| Kaiser D, Videnov G, Maichle-Mössmer C, Strähle J, Jung G (2000) X-ray structures and ab initio study of the conformational properties of novel oxazole and thiazole containing di- and tripeptide mimetics. J Chem Soc Perkin Trans 2: 1081-1085 |
| Kawamoto K, Ishimoto SI, Minoda R, Brough DE, Raphael Y (2003) Math1 gene transfer generates new cochlear hair cells in mature guinea pigs in vivo. J Neurosci 23: 4395-4400 |
| Kelley MW, Talreja DR, Corwin JT (1995) Replacement of hair cells after laser microbeam irradiation in cultured organs of Corti from embryonic and neonatal mice. J Neurosci 15: 3013-3026 |
| Kim S, Rosania GR, Chang YT (2004) Dedifferentiation? What's next? Mol Interv 4: 83-85 |
| Li H, Liu H, Heller S (2003) Pluripotent stem cells from the adult mouse inner ear. Nat Med 9: 1293-1299 |
| Li W, Ding S (2009) Small molecules that modulate embryonic stem cell fate and somatic cell reprogramming. Trends Pharmacol Sci Nov 4 |
| Martinez-Monedero R, Edge AS (2007) Stem cells for the replacement of inner ear neurons and hair cells. Int J Dev Biol 51: 655-661 |
| Martinez-Monedero R, Oshima K, Heller S, Edge AS (2007) The potential role of endogenous stem cells in regeneration of the inner ear. Hear Res 227: 48-52 |
| McGann CJ, Odelberg SJ, Keating MT (2001) Mammalian myotube dedifferentiation induced by new regeneration extract. Proc Natl Acad Sci USA 98(24): 13699-13704 |
| Nadol JB Jr (1993) Hearing Loss. N Engl J Med 329: 1092-1102 |
| Naito Y, Nakamura T Nakagawa T, Iguchi F, Endo T, Fujino K, Kim PS, Hiratsuka Y, Tamura T, Kanemaru S, Shimizu Y, Ito J (2004) Transplantation of bone marrow stromal cells into the cochlea of chinchillas. Neuroreport 15: 1-4 |
| Odelberg SJ (2002) Inducing cellular dedifferentiation: a potential method for enhancing endogenous regeneration in mammals. Semin Cell Dev Biol 13(5): 335-343 |
| Oshima K, Grimm CM, Corrales CE, Senn P, Martinez-Monedero R, Géléoc GS, Edge A, Holt JR, Heller S (2007) Differential distribution of stem cells in the auditory and vestibular organs of the inner ear. J Assoc Res Otolaryngol 8: 18-31 |
| Roberson DW, Rubel EW (1994) Cell devision in the gerbil cochlea after acoustic trauma. Am J Otol 15: 28-34 |
| Ruben RJ (1967) Development of the inner ear of the mouse. A autoradiographic study of terminal mitosis. Acta Otolaryngol (Stockh) [Suppl] 220: 1-44 |
| Ryals BM, Rubel EW (1988) Hair cell regeneration after acoustic trauma in adult Coturnix Quail. Science 240: 1774-1776 |
| Schugar RC, Robbins PD, Deasy BM (2008) Small molecules in stem cell self-renewal and differentiation. Gene Ther 15(2): 126-135 |
| Senn P, Oshima K, Teo D, Grimm C, Heller S (2007) Robust postmortem survival of murine vestibular and cochlear stem cells. J Assoc Res Otolaryngol 8(2): 194-204 |
| Smolders JWT (1999) Functional recovery in the avian ear after hair cell regeneration. Audiol Neurootol 4: 286-302 |
| Staecker H, Lefebvre PP, Malgrange B, Moonen G, Van De Water TR (1995) Technical comments: Regeneration and mammalian auditory hair cells. Science 267(5198): 709-711 |
| Stanchev M, Tabakova S, Videnov G, Golovinsky E, Jung G (1999) Synthesis and antimicrobial activity in vitro of new amino acids and peptides containing thiazole and oxazole moieties. Arch Pharm 332: 297-304 |
| Stankova IG, Videnov GI, Golovinsky EV, Jung G (1999) Synthesis of thiazole, imidazole and oxazole containing amino acids for peptide backbone modification. J Peptide Sci 5: 392-398 |
| Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4): 663-76 |
| Tateya I, Nakagawa T, Iguchi F, Kim TS, Endo T, Yamada S, Kageyama R, Anito Y, Ito J (2003) Fate of neural stem cells grafted into injured inner ears of mice. Neuroreport 14: 1677-1681 |
| Tsonis PA (2000) Regeneration in vertebrates. Dev Biol 221(2): 273-284 |
| Tsonis PA (2002) Regenerative biology: the emerging field of tissue repair and restoration. Differentiation 70(8): 397-409 |
| Tsonis PA (2004) Stem cells from differentiated cells. Mol Interv 4(2): 81-83 |
| Vago P, Humbert G, Lenoir M (1998) Amikacin intoxication induces apoptosis and cell proliferation in rat organ of Corti. Neuroreport 9: 431-436 |
| Videnov G, Kaiser D, Kempter, C, Jung G (1996) Synthesis of naturally occuring, conformationally restricted oxazole- and thiazole containing di- and tripeptide mimetics. Angew Chem Int Ed Engl 35(13/14): 1503- |
| White PM, Doetzlhofer A, Lee YS, Groves AK, Segil N (2006) Mammalian cochlear supporting cells can divide and trans-differentiate into hair cells. Nature 441: 984-987 |
| Xu Y, Shi Y, Ding S (2008) A chemical approach to stem-cell biology and regenerative medicine. Nature 453(7193): 338-344 |
| Yamasoba T, Kondo K (2006) Supporting cell proliferation after hair cell injury in mature guinea pig cochlea in vivo. Cell Tissue Res 325: 23-31 |
| Yamasoba T, Kondo K, Miyajima C, Suzuki M (2003) Changes in cell proliferation in rat and guinea pig cochlea after aminoglycoside-induced damage. Neurosci Lett 347: 171-174 |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3366683A1 (en) * | 2017-02-28 | 2018-08-29 | Acousia Therapeutics GmbH | Cyclic amides, acteamides and ureas useful as potassium channel openers |
| US11034665B2 (en) | 2017-02-28 | 2021-06-15 | Acousia Therapeutics Gmbh | Compounds useful as potassium channel openers |
Also Published As
| Publication number | Publication date |
|---|---|
| US8889723B2 (en) | 2014-11-18 |
| CN102947281A (zh) | 2013-02-27 |
| CA2789013A1 (en) | 2011-08-11 |
| EP2534139A1 (de) | 2012-12-19 |
| WO2011095338A1 (de) | 2011-08-11 |
| CN102947281B (zh) | 2015-11-25 |
| US20140288135A1 (en) | 2014-09-25 |
| JP2013518917A (ja) | 2013-05-23 |
| US20130012514A1 (en) | 2013-01-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69734215T2 (de) | Verbindungen mit Wachstumshormon-freisetzenden Eigenschaften | |
| DE60113823T3 (de) | Kleine organische moleküle als regulatoren der zellproliferation | |
| DE69703449T2 (de) | Neuroaktive peptide | |
| US20210244768A1 (en) | Cell compositions and uses thereof | |
| KR20100024951A (ko) | 세포를 자극하기 위한 방법 및 조성물 | |
| WO2021074126A1 (de) | Herstellung von skelettmuskelzellen und skelettmuskelgewebe aus pluripotenten stammzellen | |
| UA78225C2 (en) | Small organic molecule regulators of cell proliferation | |
| EP4146796A1 (en) | Methods for differentiating stem cells into dopaminergic progenitor cells | |
| DE102007009264A1 (de) | 9-Alkyl-ß-Carboline zur Behandlung von neurodegenerativen Erkrankungen | |
| DE102010007281A1 (de) | Neue Aminoalkyl-oxazol- und Aminoalkyl-thiazolcarbonsäureamide und ihre Anwendung zur Stimulation der endogenen situ Regeneration von Haarsinneszellen im Corti'schen Organ des Innenohres beim Säuger | |
| JP7542258B2 (ja) | 細胞の機械的恒常性を破壊し、組織器官の再生と修復を促進する方法、およびその使用 | |
| DE2063996C3 (de) | Alpha-Aminoxyhydroxamsäurederivate, Verfahren zur Herstellung derselben und diese enthaltende Arzneimittel | |
| JP7297271B2 (ja) | 末梢神経障害の治療及び/又は予防用組成物 | |
| AU2023271613A1 (en) | Pharmaceutical composition for preventing and treating geriatric diseases comprising neural stem cells derived from three-dimensional hypothalamus organoid and use thereof | |
| EP2673287B1 (de) | Aminostatin-derivate zur behandlung von arthrose | |
| US20240060040A1 (en) | Methods for generating inner ear hair cells | |
| CN115477650B (zh) | 一种异喹啉生物碱化合物及其制备方法和应用 | |
| EP1267916A2 (de) | Arzneimittel enthaltend tissue inhibitor of metalloproteinases-2 (timp-2) als osteoanabol wirksame substanz | |
| KR101117129B1 (ko) | 신규한 퀴녹살린 유도체 및 이를 포함하는 줄기세포의 신경세포로의 분화유도용 조성물 | |
| KR100487112B1 (ko) | 백강잠 101a로부터 분리, 정제한 뇌신경성장 촉진물질(4e, 6e, 2s,3r)-2-n-아이코사노일-4,6-테트라데카스핀게닌 | |
| CN108836955A (zh) | 对羟基苯甲醛在制备神经修复药物中的用途 | |
| US20200397901A1 (en) | Photoresponsive smoothened ligand | |
| DE202018102553U1 (de) | Zusammensetzung zur Förderung des Haarwachstums | |
| KR100487113B1 (ko) | 백강잠 101a로부터 분리, 정제한 뇌신경성장 촉진물질(4e, 6e, 2s,3r)-2-n-도코사노일-4,6-테트라데카스핀가디에닌 | |
| Mazurek et al. | Regeneration und Zelltod von Sinneszellen der Cochlea und des Vestibularorgans |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| R119 | Application deemed withdrawn, or ip right lapsed, due to non-payment of renewal fee |