RU2723091C2 - Олигонуклеотидные последовательности, нацеленные на транскрипционный фактор tsc22d4, для лечения резистентности к инсулину - Google Patents
Олигонуклеотидные последовательности, нацеленные на транскрипционный фактор tsc22d4, для лечения резистентности к инсулину Download PDFInfo
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| EP15160259.6A EP3072969A1 (en) | 2015-03-23 | 2015-03-23 | Oligonucleotide sequences targeting transcription factor TSC22D4 for the treatment of insulin resistance |
| EP15160259.6 | 2015-03-23 | ||
| PCT/EP2016/053050 WO2016150618A1 (en) | 2015-03-23 | 2016-02-12 | Oligonucleotide sequences targeting transcription factor tsc22d4 for the treatment of insulin resistance |
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| RU2017131900A3 RU2017131900A3 (enExample) | 2019-06-10 |
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| JP7289510B2 (ja) * | 2019-05-08 | 2023-06-12 | 国立大学法人高知大学 | 認知症治療薬のスクリーニング方法 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000074634A2 (en) * | 1999-06-03 | 2000-12-14 | Au Jessie L S | Methods and compositions for modulating cell proliferation and cell death |
| US7943306B2 (en) * | 2005-01-12 | 2011-05-17 | The Board Of Trustees Of The Leland Stanford Junior University | Gene expression signature for prediction of human cancer progression |
| WO2014202602A1 (en) * | 2013-06-17 | 2014-12-24 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Treatment of insulin resistance through inhibitors of transcription factor tsc22d4 |
| RU2573450C1 (ru) * | 2014-08-11 | 2016-01-20 | Федеральное Государственное Бюджетное Учреждение Науки Институт Молекулярной Биологии Им. В.А. Энгельгардта Российской Академии Наук (Имб Ран) | Способ выявления генов-мишеней для диагностики и терапии лейкозов человека |
Family Cites Families (5)
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| DK2284266T3 (da) * | 2002-11-14 | 2014-01-13 | Thermo Fisher Scient Biosciences Inc | sIRNA-MOLEKYLE MOD TP53 |
| JP4869942B2 (ja) | 2003-12-11 | 2012-02-08 | ベス・イスラエル・ディーコネス・メディカル・センター，インコーポレイテッド | インスリン感受性／抵抗性、糖尿病および肥満におけるｒｂｐ４ |
| AU2005248147A1 (en) * | 2004-05-11 | 2005-12-08 | Alphagen Co., Ltd. | Polynucleotides for causing RNA interference and method for inhibiting gene expression using the same |
| US20140227289A1 (en) | 2011-05-13 | 2014-08-14 | Stephen Michael Cohen | Compounds and methods for treating insulin resistance syndrome |
| GB201120317D0 (en) | 2011-11-24 | 2012-01-04 | Queen Mary & Westfield College | Screening method |
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2015
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000074634A2 (en) * | 1999-06-03 | 2000-12-14 | Au Jessie L S | Methods and compositions for modulating cell proliferation and cell death |
| US7943306B2 (en) * | 2005-01-12 | 2011-05-17 | The Board Of Trustees Of The Leland Stanford Junior University | Gene expression signature for prediction of human cancer progression |
| WO2014202602A1 (en) * | 2013-06-17 | 2014-12-24 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Treatment of insulin resistance through inhibitors of transcription factor tsc22d4 |
| RU2573450C1 (ru) * | 2014-08-11 | 2016-01-20 | Федеральное Государственное Бюджетное Учреждение Науки Институт Молекулярной Биологии Им. В.А. Энгельгардта Российской Академии Наук (Имб Ран) | Способ выявления генов-мишеней для диагностики и терапии лейкозов человека |
Non-Patent Citations (3)
| Title |
|---|
| /emmm.201201869. * |
| Allan Jones et al. "TSC22D4 is a molecular output of hepatic wasting metabolism" EMBO Mol Med (2013) 5, 294-308 * |
| Allan Jones et al. "TSC22D4 is a molecular output of hepatic wasting metabolism" EMBO Mol Med (2013) 5, 294-308 DOI 10.1002/emmm.201201869. * |
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| EP3274455B1 (en) | 2020-10-14 |
| BR112017016021A2 (pt) | 2018-03-20 |
| CA2979115A1 (en) | 2016-09-29 |
| RU2017131900A3 (enExample) | 2019-06-10 |
| WO2016150618A1 (en) | 2016-09-29 |
| KR20170128348A (ko) | 2017-11-22 |
| JP2018513841A (ja) | 2018-05-31 |
| EP3072969A1 (en) | 2016-09-28 |
| DK3274455T3 (da) | 2020-12-14 |
| US10676739B2 (en) | 2020-06-09 |
| US20180023078A1 (en) | 2018-01-25 |
| CN107278229A (zh) | 2017-10-20 |
| ES2837085T3 (es) | 2021-06-29 |
| MX384193B (es) | 2025-03-12 |
| RU2017131900A (ru) | 2019-04-23 |
| US20200255834A1 (en) | 2020-08-13 |
| US11053499B2 (en) | 2021-07-06 |
| EP3274455A1 (en) | 2018-01-31 |
| MX2017012231A (es) | 2018-01-30 |
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