JP2011503103A - タンパク質輸送の調節方法 - Google Patents
タンパク質輸送の調節方法 Download PDFInfo
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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| IL305584A (en) * | 2021-03-03 | 2023-10-01 | Inst Biologii Doswiadczalnej Imienia Marcelego Nenckiego Polskiej Akademii Nauk | Protein kinase D inhibitor for use in the prevention or treatment of hyperlipidemia |
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| ES3038124T3 (en) * | 2023-05-09 | 2025-10-09 | Molecular Horizon S R L | Phenylpyrazole insecticide compounds and compositions |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6342501B1 (en) * | 1994-02-25 | 2002-01-29 | The Regents Of The University Of Michigan | Pyrrolo[2,3-d] pyrimidines as antiviral agents |
| US20040248906A1 (en) * | 2001-08-10 | 2004-12-09 | Donato Nicholas J | Use of c-src inhibitors alone or in combination with st1571 for the treatment of leukaemia |
| WO2003082341A1 (en) * | 2002-03-22 | 2003-10-09 | Cellular Genomics, Inc. | AN IMPROVED FORMULATION OF CERTAIN PYRAZOLO[3,4-d] PYRIMIDINES AS KINASE MODULATORS |
| UA80171C2 (en) * | 2002-12-19 | 2007-08-27 | Pfizer Prod Inc | Pyrrolopyrimidine derivatives |
| JP2007505158A (ja) * | 2003-05-21 | 2007-03-08 | ボード オブ リージェンツ ザ ユニバーシティー オブ テキサス システム | 心肥大および心不全の処置としてのプロテインキナーゼＣ−μ（ＰＫＤ）の阻害 |
| US7429596B2 (en) * | 2003-06-20 | 2008-09-30 | The Regents Of The University Of California | 1H-pyrrolo [2,3-D] pyrimidine derivatives and methods of use thereof |
| WO2005112936A1 (en) * | 2004-05-14 | 2005-12-01 | The Regents Of The University Of Michigan | Compositions and methods relating to protein kinase inhibitors |
| US20060094682A1 (en) * | 2004-10-29 | 2006-05-04 | Odyssey Thera, Inc. | Kinase inhibitors for the treatment of diabetes and obesity |
| WO2006068760A2 (en) * | 2004-11-19 | 2006-06-29 | The Regents Of The University Of California | Anti-inflammatory pyrazolopyrimidines |
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| US20100160339A1 (en) * | 2007-05-21 | 2010-06-24 | Mayo Foundation For Medical Education And Research | Treating pancreatitis |
-
2008
- 2008-11-07 CA CA2705303A patent/CA2705303A1/en not_active Abandoned
- 2008-11-07 EA EA201070572A patent/EA201070572A1/ru unknown
- 2008-11-07 JP JP2010533304A patent/JP2011503103A/ja not_active Withdrawn
- 2008-11-07 CN CN200880124202XA patent/CN101917999A/zh active Pending
- 2008-11-07 AU AU2008323694A patent/AU2008323694A1/en not_active Abandoned
- 2008-11-07 WO PCT/US2008/082909 patent/WO2009062118A2/en not_active Ceased
- 2008-11-07 US US12/741,992 patent/US20100331297A1/en not_active Abandoned
- 2008-11-07 BR BRPI0820342-3A patent/BRPI0820342A2/pt not_active IP Right Cessation
- 2008-11-07 EP EP08848219A patent/EP2217239A2/en not_active Withdrawn
-
2010
- 2010-05-25 ZA ZA2010/03725A patent/ZA201003725B/en unknown
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Also Published As
| Publication number | Publication date |
|---|---|
| EA201070572A1 (ru) | 2010-12-30 |
| CA2705303A1 (en) | 2009-05-14 |
| ZA201003725B (en) | 2011-03-30 |
| CN101917999A (zh) | 2010-12-15 |
| WO2009062118A3 (en) | 2009-12-30 |
| WO2009062118A2 (en) | 2009-05-14 |
| US20100331297A1 (en) | 2010-12-30 |
| EP2217239A2 (en) | 2010-08-18 |
| BRPI0820342A2 (pt) | 2015-05-26 |
| AU2008323694A1 (en) | 2009-05-14 |
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