JP7213188B2 - Ｓｔｉｎｇアゴニストとしての環状ジヌクレオチド - Google Patents
Ｓｔｉｎｇアゴニストとしての環状ジヌクレオチド Download PDFInfo
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- JP7213188B2 JP7213188B2 JP2019540532A JP2019540532A JP7213188B2 JP 7213188 B2 JP7213188 B2 JP 7213188B2 JP 2019540532 A JP2019540532 A JP 2019540532A JP 2019540532 A JP2019540532 A JP 2019540532A JP 7213188 B2 JP7213188 B2 JP 7213188B2
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Classifications
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- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
- A61K31/708—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7084—Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
Landscapes
- Health & Medical Sciences (AREA)
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- Molecular Biology (AREA)
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- Animal Behavior & Ethology (AREA)
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- Medicinal Chemistry (AREA)
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- Pharmacology & Pharmacy (AREA)
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- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicinal Preparation (AREA)
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| IL280430B2 (en) | 2016-03-18 | 2023-11-01 | Univ Texas | Cyclic dinucleotide compounds and methods of use |
| WO2018100558A2 (en) | 2016-12-01 | 2018-06-07 | Takeda Pharmaceutical Company Limited | Cyclic dinucleotide |
| TWI808092B (zh) | 2017-08-30 | 2023-07-11 | 中國大陸商北京軒義醫藥科技有限公司 | 作為干擾素基因調節劑之刺激劑的環狀二核苷酸 |
| PH12020550585A1 (en) | 2017-11-10 | 2021-04-19 | Takeda Pharmaceuticals Co | Sting modulator compounds, and methods of making and using |
| US11110106B2 (en) | 2018-10-29 | 2021-09-07 | Venenum Biodesign, LLC | Sting agonists for treating bladder cancer and solid tumors |
| EP3873484B1 (en) | 2018-10-29 | 2023-08-23 | Venenum Biodesign, LLC | Novel sting agonists |
| EP3883651A1 (en) * | 2018-11-19 | 2021-09-29 | IFM Due, Inc. | Compounds and compositions for treating conditions associated with sting activity |
| MA55805A (fr) | 2019-05-03 | 2022-03-09 | Flagship Pioneering Innovations V Inc | Métodes de modulation de l'activité immunitaire |
| CN114127082A (zh) * | 2019-05-09 | 2022-03-01 | 阿里戈斯治疗公司 | 作为sting调节剂的经修饰的环状二核苷化合物 |
| WO2021007160A1 (en) | 2019-07-05 | 2021-01-14 | Tambo, Inc. | Trans-cyclooctene bioorthogonal agents and uses in cancer and immunotherapy |
| US20230141284A1 (en) | 2020-04-10 | 2023-05-11 | Ono Pharmaceutical Co., Ltd. | Cancer therapeutic method |
| US20230210968A1 (en) * | 2020-06-11 | 2023-07-06 | Massachusetts Institute Of Technology | Ribonucleoprotein approach to boost the sting signaling for cancer immunotherapy |
| JP2023537066A (ja) | 2020-08-07 | 2023-08-30 | タンボ・インコーポレイテッド | トランス－シクロオクテン生体直交型薬剤並びに癌及び免疫療法における使用 |
| JP7397996B2 (ja) | 2020-11-09 | 2023-12-13 | 武田薬品工業株式会社 | 抗体薬物コンジュゲート |
| AU2022326463A1 (en) | 2021-08-10 | 2024-02-22 | Novartis Pharma Ag | Compounds and compositions for treating conditions associated with sting activity |
| CN120757600B (zh) * | 2025-09-10 | 2025-11-11 | 天津法尔玛制药有限公司 | 环二核苷酸2′,3′-cG4′-MeAMP、制备方法及其在制备先天免疫激活剂中的应用 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016100261A2 (en) | 2014-12-17 | 2016-06-23 | Lipogen Llc | Method of treating cancer with cgamp or cgasmp |
| JP2016524593A (ja) | 2013-04-29 | 2016-08-18 | メモリアル スローン−ケタリング キャンサー センター | セカンドメッセンジャーのシグナル伝達を変えるための組成物及び方法 |
| JP2018522914A (ja) | 2015-08-13 | 2018-08-16 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | Ｓｔｉｎｇアゴニストとしての環状ジヌクレオチド化合物 |
| JP2020500862A (ja) | 2016-11-25 | 2020-01-16 | ヤンセン バイオテツク，インコーポレーテツド | Ｓｔｉｎｇアゴニストとしての環状ジヌクレオチド |
| JP2020503303A (ja) | 2016-12-20 | 2020-01-30 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | がんの処置のための環状ジヌクレオチドｓｔｉｎｇアゴニスト |
| JP2020511420A (ja) | 2016-12-20 | 2020-04-16 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | がんの処置のためのｐｄ−１アンタゴニストと環状ジヌクレオチドｓｔｉｎｇアゴニストとの組み合わせ |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020142000A1 (en) | 1999-01-15 | 2002-10-03 | Digan Mary Ellen | Anti-CD3 immunotoxins and therapeutic uses therefor |
| PE20010306A1 (es) | 1999-07-02 | 2001-03-29 | Agouron Pharma | Compuestos de indazol y composiciones farmaceuticas que los contienen utiles para la inhibicion de proteina kinasa |
| TWI262914B (en) | 1999-07-02 | 2006-10-01 | Agouron Pharma | Compounds and pharmaceutical compositions for inhibiting protein kinases |
| GB0018891D0 (en) | 2000-08-01 | 2000-09-20 | Novartis Ag | Organic compounds |
| AU2002234755A1 (en) | 2001-02-26 | 2002-09-12 | Pharma Pacific Pty Ltd | Interferon-alpha induced gene |
| EP1645561A1 (en) * | 2003-07-15 | 2006-04-12 | Mitsui Chemicals, Inc. | Method of synthesizing cyclic bisdinucleoside |
| KR101704734B1 (ko) | 2005-07-01 | 2017-02-09 | 이. 알. 스퀴부 앤드 선즈, 엘.엘.씨. | 예정 사멸 리간드 1 (피디-엘1)에 대한 인간 모노클로날 항체 |
| WO2010098788A2 (en) | 2008-08-25 | 2010-09-02 | Amplimmune, Inc. | Pd-i antagonists and methods for treating infectious disease |
| MX356367B (es) | 2008-12-09 | 2018-05-25 | Genentech Inc | Anticuerpos anti-pd-l1 y su uso para mejorar la funcion de celulas t. |
| EP2504028A4 (en) | 2009-11-24 | 2014-04-09 | Amplimmune Inc | SIMULTANEOUS INHIBITION OF PD-L1 / PD-L2 |
| BR112014002353B1 (pt) | 2011-08-01 | 2022-09-27 | Genentech, Inc | Usos de antagonistas de ligação do eixo pd-1 e inibidores de mek, composições farmacêuticas, e kit |
| CU24377B1 (es) | 2013-05-18 | 2018-12-05 | Aduro Biotech Inc | Dinucléotidos de purina cíclicos y composiciones de los mismos útiles para inducir la producción de interferón de tipo i dependientes de sting |
| EP2996472B1 (en) | 2013-05-18 | 2019-03-27 | Aduro Biotech, Inc. | Compositions and methods for inhibiting "stimulator of interferon gene" dependent signalling |
| JP2016538344A (ja) | 2013-11-19 | 2016-12-08 | ザ・ユニバーシティ・オブ・シカゴＴｈｅ Ｕｎｉｖｅｒｓｉｔｙ Ｏｆ Ｃｈｉｃａｇｏ | 癌処置としてのｓｔｉｎｇアゴニストの使用 |
| EP3152217B1 (en) | 2014-06-04 | 2018-08-01 | GlaxoSmithKline Intellectual Property Development Limited | Cyclic di-nucleotides as modulators of sting |
| GB201501462D0 (en) | 2015-01-29 | 2015-03-18 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| KR20180066241A (ko) | 2015-10-28 | 2018-06-18 | 아두로 바이오테크, 인코포레이티드 | “인터페론 유전자의 자극제”-의존성 신호전달을 활성화시키기 위한 조성물 및 방법 |
| JP6411676B2 (ja) | 2015-12-03 | 2018-10-24 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ | Ｓｔｉｎｇの調節因子としての環状プリンジヌクレオチド |
| IL280430B2 (en) | 2016-03-18 | 2023-11-01 | Univ Texas | Cyclic dinucleotide compounds and methods of use |
| WO2017186711A1 (en) | 2016-04-25 | 2017-11-02 | Invivogen | Novel complexes of immunostimulatory compounds, and uses thereof |
| EP3507367A4 (en) * | 2016-07-05 | 2020-03-25 | Aduro BioTech, Inc. | CYCLIC DINUCLEOTID COMPOUNDS WITH INCLUDED NUCLEIC ACIDS AND USES THEREOF |
-
2018
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2022
- 2022-08-15 JP JP2022129286A patent/JP2022163188A/ja active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016524593A (ja) | 2013-04-29 | 2016-08-18 | メモリアル スローン−ケタリング キャンサー センター | セカンドメッセンジャーのシグナル伝達を変えるための組成物及び方法 |
| WO2016100261A2 (en) | 2014-12-17 | 2016-06-23 | Lipogen Llc | Method of treating cancer with cgamp or cgasmp |
| JP2018522914A (ja) | 2015-08-13 | 2018-08-16 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | Ｓｔｉｎｇアゴニストとしての環状ジヌクレオチド化合物 |
| JP2020500862A (ja) | 2016-11-25 | 2020-01-16 | ヤンセン バイオテツク，インコーポレーテツド | Ｓｔｉｎｇアゴニストとしての環状ジヌクレオチド |
| JP2020503303A (ja) | 2016-12-20 | 2020-01-30 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | がんの処置のための環状ジヌクレオチドｓｔｉｎｇアゴニスト |
| JP2020511420A (ja) | 2016-12-20 | 2020-04-16 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | がんの処置のためのｐｄ−１アンタゴニストと環状ジヌクレオチドｓｔｉｎｇアゴニストとの組み合わせ |
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| AU2018212787A1 (en) | 2019-07-25 |
| AU2018212787B2 (en) | 2023-10-26 |
| US11021511B2 (en) | 2021-06-01 |
| WO2018138684A1 (en) | 2018-08-02 |
| JP2022163188A (ja) | 2022-10-25 |
| US20190375781A1 (en) | 2019-12-12 |
| EP3573717B1 (en) | 2021-07-28 |
| JP2020514316A (ja) | 2020-05-21 |
| ES2891326T3 (es) | 2022-01-27 |
| EP3573717A1 (en) | 2019-12-04 |
| CN110234404A (zh) | 2019-09-13 |
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