CN111803635B - 小分子抑制剂在治疗呼吸道病毒性肺炎上的应用 - Google Patents
小分子抑制剂在治疗呼吸道病毒性肺炎上的应用 Download PDFInfo
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| PCT/CN2020/113478 WO2021253647A1 (fr) | 2020-06-17 | 2020-09-04 | Utilisation d'un inhibiteur de petites molécules dans le traitement de la pneumonie virale respiratoire |
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| CN202010919429.6A Active CN113797337B (zh) | 2020-06-17 | 2020-09-04 | 小分子抑制剂在预防及治疗呼吸道病毒性肺炎中的应用 |
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| CN119258221B (zh) * | 2024-12-11 | 2025-04-04 | 吉林大学 | AhR激动剂在制备治疗放射性肺炎药物中的应用 |
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| CN103169970A (zh) * | 2011-12-25 | 2013-06-26 | 复旦大学 | 一种治疗病毒性肺炎的药物组合物 |
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| CA2375647A1 (fr) * | 1999-07-08 | 2001-01-18 | Patrick T. Prendergast | Utilisation de flavones, de coumarines et de composes associes dans le traitement d'infections |
| EP1418164A1 (fr) * | 2002-11-07 | 2004-05-12 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Nouveaux derivés de stilbène et leur utilisation en tant que antagonistes des ligands du recepteur des arylhydrocarbures |
| CN107648216B (zh) * | 2010-07-27 | 2021-03-30 | 波士顿大学管理委员会 | 作为新型癌症疗法的芳烃受体(AhR)调节剂 |
| NO2694640T3 (fr) * | 2011-04-15 | 2018-03-17 | ||
| US9175266B2 (en) * | 2012-07-23 | 2015-11-03 | Gamida Cell Ltd. | Enhancement of natural killer (NK) cell proliferation and activity |
| MX388871B (es) * | 2014-06-27 | 2025-03-20 | Nogra Pharma Ltd | Moduladores del receptor arilo y metodos para elaborar y usar los mismos. |
| EP3193917B9 (fr) * | 2014-09-17 | 2022-02-16 | IO Biotech ApS | Vaccins comprenants la tryptophane 2,3-dioxygénase (tdo) ou des fragments de la tdo |
| GB201417369D0 (en) * | 2014-10-01 | 2014-11-12 | Redx Pharma Ltd | Compounds |
| CN106860471A (zh) * | 2015-12-13 | 2017-06-20 | 复旦大学 | 一种AhR受体蛋白抑制剂在制备抗病毒药物中的用途 |
| US10640499B2 (en) * | 2016-09-02 | 2020-05-05 | Gilead Sciences, Inc. | Toll like receptor modulator compounds |
| BR112020004586A2 (pt) * | 2017-09-08 | 2020-09-08 | Insignis Therapeutics, Inc. | métodos para uso da dipivefrina |
| CN111166734A (zh) * | 2020-02-27 | 2020-05-19 | 黄铭 | 萘醌类物质治疗病原性生物引起的肺炎的用途 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103169970A (zh) * | 2011-12-25 | 2013-06-26 | 复旦大学 | 一种治疗病毒性肺炎的药物组合物 |
Non-Patent Citations (3)
| Title |
|---|
| A potential role for AHR in SARS-CoV-2 pathology;F Giovannoni 等;《Research Square》;20200427;第2页"摘要",第2页倒数第1段至第3页第3段,第4页第3段 * |
| Indoleamine 2,3-Dioxygenase (IDO) Activity During the Primary Immune Response to Influenza Infection Modifies the Memory T Cell Response to Influenza Challenge;Leo K. Sage 等;《VIRAL IMMUNOLOGY》;20141231;摘要,第113页左栏第4段,第115页左栏"结果" * |
| Murine Coronavirus Infection Activates the Aryl Hydrocarbon Receptor in an Indoleamine 2,3-Dioxygenase-Independent Manner, Contributing to Cytokine Modulation and Proviral TCDD-Inducible-PARP Expression;Matthew E. Grunewald 等;《Journal of Virology》;20200228;摘要,第2页图1说明 * |
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| Publication number | Publication date |
|---|---|
| WO2021253647A1 (fr) | 2021-12-23 |
| CN113797337A (zh) | 2021-12-17 |
| CN111803635A (zh) | 2020-10-23 |
| CN113797337B (zh) | 2023-02-07 |
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