JP2023025065A5 - - Google Patents
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- JP2023025065A5 JP2023025065A5 JP2022183436A JP2022183436A JP2023025065A5 JP 2023025065 A5 JP2023025065 A5 JP 2023025065A5 JP 2022183436 A JP2022183436 A JP 2022183436A JP 2022183436 A JP2022183436 A JP 2022183436A JP 2023025065 A5 JP2023025065 A5 JP 2023025065A5
- Authority
- JP
- Japan
- Prior art keywords
- inhibitors
- skeletal muscle
- muscle damage
- myotubes
- therapeutic agent
- 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.)
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- 238000000034 method Methods 0.000 claims 10
- 208000029549 Muscle injury Diseases 0.000 claims 5
- 210000002027 skeletal muscle Anatomy 0.000 claims 5
- 230000002485 urinary effect Effects 0.000 claims 5
- 239000003814 drug Substances 0.000 claims 4
- 239000003112 inhibitor Substances 0.000 claims 4
- 229940124597 therapeutic agent Drugs 0.000 claims 4
- 101150013833 MYOD1 gene Proteins 0.000 claims 3
- UNSKMHKAFPRFTI-FDKLLANESA-N (1s,2r,5r)-5-(4-aminoimidazo[4,5-c]pyridin-1-yl)-3-(hydroxymethyl)cyclopent-3-ene-1,2-diol;hydrochloride Chemical compound Cl.C1=NC=2C(N)=NC=CC=2N1[C@@H]1C=C(CO)[C@@H](O)[C@H]1O UNSKMHKAFPRFTI-FDKLLANESA-N 0.000 claims 2
- 102000008157 Histone Demethylases Human genes 0.000 claims 2
- 108010074870 Histone Demethylases Proteins 0.000 claims 2
- 102000011787 Histone Methyltransferases Human genes 0.000 claims 2
- 108010036115 Histone Methyltransferases Proteins 0.000 claims 2
- 239000012661 PARP inhibitor Substances 0.000 claims 2
- 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 claims 2
- 102000000477 Sirtuin 2 Human genes 0.000 claims 2
- 108010041216 Sirtuin 2 Proteins 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 claims 2
- 239000013604 expression vector Substances 0.000 claims 2
- 239000003276 histone deacetylase inhibitor Substances 0.000 claims 2
- 229940121372 histone deacetylase inhibitor Drugs 0.000 claims 2
- 239000003697 methyltransferase inhibitor Substances 0.000 claims 2
- MYTRGTBDVGKKRO-UHFFFAOYSA-N 1-(1,2,3-benzothiadiazol-6-yl)-3-(2-oxo-2-piperidin-1-ylethyl)urea Chemical compound C=1C=C2N=NSC2=CC=1NC(=O)NCC(=O)N1CCCCC1 MYTRGTBDVGKKRO-UHFFFAOYSA-N 0.000 claims 1
- DMIDPTCQPIJYFE-UHFFFAOYSA-N 1-isoquinolin-6-yl-3-(2-oxo-2-pyrrolidin-1-ylethyl)urea Chemical compound C=1C=C2C=NC=CC2=CC=1NC(=O)NCC(=O)N1CCCC1 DMIDPTCQPIJYFE-UHFFFAOYSA-N 0.000 claims 1
- MENNDDDTIIZDDN-UHFFFAOYSA-N 2-(4,6-dimethylpyrimidin-2-yl)sulfanyl-n-[5-(naphthalen-1-ylmethyl)-1,3-thiazol-2-yl]acetamide Chemical compound CC1=CC(C)=NC(SCC(=O)NC=2SC(CC=3C4=CC=CC=C4C=CC=3)=CN=2)=N1 MENNDDDTIIZDDN-UHFFFAOYSA-N 0.000 claims 1
- AVZCPICCWKMZDT-UHFFFAOYSA-N 3-[[2-(2-pyridinyl)-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)-4-pyrimidinyl]amino]propanoic acid Chemical compound N=1C(NCCC(=O)O)=CC(N2CCC3=CC=CC=C3CC2)=NC=1C1=CC=CC=N1 AVZCPICCWKMZDT-UHFFFAOYSA-N 0.000 claims 1
- OMKHWTRUYNAGFG-IEBDPFPHSA-N 3-deazaneplanocin a Chemical compound C1=NC=2C(N)=NC=CC=2N1[C@@H]1C=C(CO)[C@@H](O)[C@H]1O OMKHWTRUYNAGFG-IEBDPFPHSA-N 0.000 claims 1
- FIHKWEQJEDRIFS-UHFFFAOYSA-N 3-n-hydroxy-1-n-(2-phenylethyl)benzene-1,3-dicarboxamide Chemical compound ONC(=O)C1=CC=CC(C(=O)NCCC=2C=CC=CC=2)=C1 FIHKWEQJEDRIFS-UHFFFAOYSA-N 0.000 claims 1
- JGRPKOGHYBAVMW-UHFFFAOYSA-N 8-hydroxy-5-quinolinecarboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=C(O)C2=N1 JGRPKOGHYBAVMW-UHFFFAOYSA-N 0.000 claims 1
- 229940122680 Demethylase inhibitor Drugs 0.000 claims 1
- ULNXAWLQFZMIHX-UHFFFAOYSA-N GSK343 Chemical compound C1=C(C)NC(=O)C(CNC(=O)C=2C=3C=NN(C=3C=C(C=2)C=2C=C(N=CC=2)N2CCN(C)CC2)C(C)C)=C1CCC ULNXAWLQFZMIHX-UHFFFAOYSA-N 0.000 claims 1
- WWGBHDIHIVGYLZ-UHFFFAOYSA-N N-[4-[3-[[[7-(hydroxyamino)-7-oxoheptyl]amino]-oxomethyl]-5-isoxazolyl]phenyl]carbamic acid tert-butyl ester Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1C1=CC(C(=O)NCCCCCCC(=O)NO)=NO1 WWGBHDIHIVGYLZ-UHFFFAOYSA-N 0.000 claims 1
- 238000001514 detection method Methods 0.000 claims 1
- 230000006718 epigenetic regulation Effects 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 claims 1
- 239000003550 marker Substances 0.000 claims 1
- 201000006938 muscular dystrophy Diseases 0.000 claims 1
- VRYZCEONIWEUAV-UHFFFAOYSA-N n-[6-(hydroxyamino)-6-oxohexoxy]-3,5-dimethylbenzamide Chemical compound CC1=CC(C)=CC(C(=O)NOCCCCCC(=O)NO)=C1 VRYZCEONIWEUAV-UHFFFAOYSA-N 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- WAEXFXRVDQXREF-UHFFFAOYSA-N vorinostat Chemical compound ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1 WAEXFXRVDQXREF-UHFFFAOYSA-N 0.000 claims 1
- 229960000237 vorinostat Drugs 0.000 claims 1
Claims (9)
- 骨格筋障害を引き起こす状態の治療薬の検定方法であって、
尿中細胞から筋管を作製する方法によって、骨格筋障害を引き起こす状態を有する患者の尿中細胞から筋管を作製する作製ステップと、
前記筋管に治療薬を適用する適用ステップと、
前記筋管における骨格筋障害を引き起こす状態の改善を検出する検出ステップと、
を含み、
前記尿中細胞から筋管を作製する方法が、前記骨格筋障害を引き起こす状態を有する患者の尿中細胞にMYOD1遺伝子を導入する導入ステップと、前記尿中細胞を少なくとも1種のエピジェネティクス制御化合物に曝露する曝露ステップとを含む、方法(但し、前記骨格筋障害を引き起こす状態の治療薬は、筋ジストロフィー患者に対するエクソン・スキップ治療薬ではない)。 - 前記エピジェネティクス制御化合物が、ヒストンメチル基転移酵素阻害剤、ヒストン脱メチル化酵素阻害剤、ヒストン脱アセチル化酵素阻害剤、SIRT2阻害剤、及びPARP阻害剤からなる群より選択される少なくとも1種を含む、請求項1に記載の方法。
- ヒストンメチル基転移酵素阻害剤が、3-デアザネプラノシンA及び3-デアザネプラノシンA塩酸塩(DZNep)、GSK343、SGC707、フラミジン二塩酸塩、UNC2327、E7438、及びMI-2(メニン-MLL阻害剤)からなる群より選択される少なくとも1種を含む、請求項2に記載の方法。
- ヒストン脱メチル化酵素阻害剤が、IOX 1及びGSK-J1からなる群より選択される少なくとも1種を含む、請求項2に記載の方法。
- ヒストン脱アセチル化酵素阻害剤が、LMK-235、CAY10603、BRD73954、及びVORINOSTATからなる群より選択される少なくとも1種を含む、請求項2に記載の方法。
- SIRT2阻害剤がSirReal 2を含む、請求項2に記載の方法。
- PARP阻害剤がEB47を含む、請求項2に記載の方法。
- 前記導入ステップにおいて、MYOD1遺伝子の導入が、誘導性プロモーターの制御下にあるMYOD1遺伝子を含む発現ベクターの導入により行われる、請求項1~7のいずれか1項に記載の方法。
- 発現ベクターが選択マーカー遺伝子をさらに含む、請求項8に記載の方法。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2022183436A JP7390694B2 (ja) | 2018-12-25 | 2022-11-16 | 随時尿中細胞を用いた筋系細胞の誘導方法 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2020561982A JP7185239B2 (ja) | 2018-12-25 | 2018-12-25 | 随時尿中細胞を用いた筋系細胞の誘導方法 |
PCT/JP2018/047447 WO2020136696A1 (ja) | 2018-12-25 | 2018-12-25 | 随時尿中細胞を用いた筋系細胞の誘導方法 |
JP2022183436A JP7390694B2 (ja) | 2018-12-25 | 2022-11-16 | 随時尿中細胞を用いた筋系細胞の誘導方法 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
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JP2020561982A Division JP7185239B2 (ja) | 2018-12-25 | 2018-12-25 | 随時尿中細胞を用いた筋系細胞の誘導方法 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2023025065A JP2023025065A (ja) | 2023-02-21 |
JP2023025065A5 true JP2023025065A5 (ja) | 2023-08-10 |
JP7390694B2 JP7390694B2 (ja) | 2023-12-04 |
Family
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Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
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JP2020561982A Active JP7185239B2 (ja) | 2018-12-25 | 2018-12-25 | 随時尿中細胞を用いた筋系細胞の誘導方法 |
JP2022183436A Active JP7390694B2 (ja) | 2018-12-25 | 2022-11-16 | 随時尿中細胞を用いた筋系細胞の誘導方法 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
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JP2020561982A Active JP7185239B2 (ja) | 2018-12-25 | 2018-12-25 | 随時尿中細胞を用いた筋系細胞の誘導方法 |
Country Status (5)
Country | Link |
---|---|
US (1) | US20220144902A1 (ja) |
JP (2) | JP7185239B2 (ja) |
AU (1) | AU2018454784A1 (ja) |
CA (1) | CA3124779A1 (ja) |
WO (1) | WO2020136696A1 (ja) |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI541024B (zh) * | 2010-09-01 | 2016-07-11 | 日本新藥股份有限公司 | 反義核酸 |
CN110079525A (zh) * | 2011-12-28 | 2019-08-02 | 日本新药株式会社 | 反义核酸 |
-
2018
- 2018-12-25 JP JP2020561982A patent/JP7185239B2/ja active Active
- 2018-12-25 AU AU2018454784A patent/AU2018454784A1/en active Pending
- 2018-12-25 CA CA3124779A patent/CA3124779A1/en active Pending
- 2018-12-25 WO PCT/JP2018/047447 patent/WO2020136696A1/ja active Application Filing
- 2018-12-25 US US17/418,203 patent/US20220144902A1/en active Pending
-
2022
- 2022-11-16 JP JP2022183436A patent/JP7390694B2/ja active Active
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