ES2891326T3 - Dinucleótidos cíclicos como agonistas de la STING - Google Patents
Dinucleótidos cíclicos como agonistas de la STING Download PDFInfo
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- ES2891326T3 ES2891326T3 ES18703857T ES18703857T ES2891326T3 ES 2891326 T3 ES2891326 T3 ES 2891326T3 ES 18703857 T ES18703857 T ES 18703857T ES 18703857 T ES18703857 T ES 18703857T ES 2891326 T3 ES2891326 T3 ES 2891326T3
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Classifications
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- 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)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762451285P | 2017-01-27 | 2017-01-27 | |
| US201762454131P | 2017-02-03 | 2017-02-03 | |
| PCT/IB2018/050497 WO2018138684A1 (en) | 2017-01-27 | 2018-01-26 | Cyclic dinucleotides as sting agonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2891326T3 true ES2891326T3 (es) | 2022-01-27 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES18703857T Active ES2891326T3 (es) | 2017-01-27 | 2018-01-26 | Dinucleótidos cíclicos como agonistas de la STING |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US11021511B2 (https=) |
| EP (1) | EP3573717B1 (https=) |
| JP (2) | JP7213188B2 (https=) |
| CN (1) | CN110234404A (https=) |
| AU (1) | AU2018212787B2 (https=) |
| ES (1) | ES2891326T3 (https=) |
| WO (1) | WO2018138684A1 (https=) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG10201912074PA (en) | 2016-03-18 | 2020-02-27 | Immune Sensor Llc | Cyclic di-nucleotide compounds and methods of use |
| WO2018100558A2 (en) | 2016-12-01 | 2018-06-07 | Takeda Pharmaceutical Company Limited | Cyclic dinucleotide |
| WO2019043634A2 (en) | 2017-08-30 | 2019-03-07 | Beijing Xuanyi Pharmasciences Co., Ltd. | CYCLIC DI-NUCLEOTIDES AS STIMULATORS OF INTERFERON GENE MODULATORS |
| JP7195317B2 (ja) | 2017-11-10 | 2022-12-23 | 武田薬品工業株式会社 | Ｓｔｉｎｇ調節剤化合物、ならびに製造及び使用する方法 |
| US11110106B2 (en) | 2018-10-29 | 2021-09-07 | Venenum Biodesign, LLC | Sting agonists for treating bladder cancer and solid tumors |
| AU2019371206A1 (en) | 2018-10-29 | 2021-05-27 | 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 |
| WO2020227159A2 (en) | 2019-05-03 | 2020-11-12 | Flagship Pioneering Innovations V, Inc. | Methods of modulating immune activity |
| JP7621974B2 (ja) * | 2019-05-09 | 2025-01-27 | アリゴス セラピューティクス インコーポレイテッド | Ｓｔｉｎｇモジュレータとしての修飾環状ジヌクレオシド化合物 |
| AU2020310853A1 (en) | 2019-07-05 | 2022-01-27 | Tambo, Inc. | Trans-cyclooctene bioorthogonal agents and uses in cancer and immunotherapy |
| WO2021206158A1 (ja) | 2020-04-10 | 2021-10-14 | 小野薬品工業株式会社 | がん治療方法 |
| WO2021252904A1 (en) * | 2020-06-11 | 2021-12-16 | Massachusetts Institute Of Technology | Ribonucleoprotein approach to boost the sting signaling for cancer immunotherapy |
| EP4295917A3 (en) | 2020-08-07 | 2024-02-28 | Tambo, Inc. | Trans-cyclooctene bioorthogonal agents and uses in cancer and immunotherapy |
| 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 |
| UY39892A (es) | 2021-08-10 | 2023-03-31 | Novartis Pharma Ag | Compuestos y composiciones para tratar afecciones asociadas con la actividad de STING |
| 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 |
Family Cites Families (28)
| 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 |
| TWI262914B (en) | 1999-07-02 | 2006-10-01 | Agouron Pharma | Compounds and pharmaceutical compositions for inhibiting protein kinases |
| 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 |
| GB0018891D0 (en) | 2000-08-01 | 2000-09-20 | Novartis Ag | Organic compounds |
| EP1368458A2 (en) | 2001-02-26 | 2003-12-10 | Pharma Pacific Pty. Ltd. | Interferon-alpha induced gene |
| US20060167241A1 (en) * | 2003-07-15 | 2006-07-27 | Mitsui Chemicals, Inc. | Method for synthesizing cyclic bisdinucleoside |
| CN104356236B (zh) | 2005-07-01 | 2020-07-03 | E.R.施贵宝&圣斯有限责任公司 | 抗程序性死亡配体1(pd-l1)的人单克隆抗体 |
| WO2010098788A2 (en) | 2008-08-25 | 2010-09-02 | Amplimmune, Inc. | Pd-i antagonists and methods for treating infectious disease |
| AU2009333580B2 (en) | 2008-12-09 | 2016-07-07 | Genentech, Inc. | Anti-PD-L1 antibodies and their use to enhance T-cell function |
| WO2011066342A2 (en) | 2009-11-24 | 2011-06-03 | Amplimmune, Inc. | Simultaneous inhibition of pd-l1/pd-l2 |
| JP6238459B2 (ja) | 2011-08-01 | 2017-11-29 | ジェネンテック， インコーポレイテッド | Ｐｄ−１軸結合アンタゴニストとｍｅｋ阻害剤を使用する癌の治療方法 |
| WO2014179335A1 (en) * | 2013-04-29 | 2014-11-06 | Memorial Sloan Kettering Cancer Center | Compositions and methods for altering second messenger signaling |
| RS59500B1 (sr) | 2013-05-18 | 2019-12-31 | Aduro Biotech Inc | Sastavi i metode za aktiviranje signaliziranja koje je zavisno od „stimulatora gena za interferon“ |
| EP2996472B1 (en) | 2013-05-18 | 2019-03-27 | Aduro Biotech, Inc. | Compositions and methods for inhibiting "stimulator of interferon gene" dependent signalling |
| US9549944B2 (en) | 2013-05-18 | 2017-01-24 | 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 |
| PE20170198A1 (es) * | 2014-06-04 | 2017-04-08 | Glaxosmithkline Ip Dev Ltd | Dinucleotidos ciclicos como moduladores de sting |
| WO2016100261A2 (en) * | 2014-12-17 | 2016-06-23 | Lipogen Llc | Method of treating cancer with cgamp or cgasmp |
| GB201501462D0 (en) | 2015-01-29 | 2015-03-18 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| CR20180101A (es) * | 2015-08-13 | 2018-04-12 | Merck Sharp & Dohme | Compuestos di-nucleóticos cíclicos como agonistas de sting |
| CA3002236A1 (en) | 2015-10-28 | 2017-05-04 | Aduro Biotech, Inc. | Compositions and methods for activating "stimulator of interferon gene"-dependent signalling |
| TWI704154B (zh) | 2015-12-03 | 2020-09-11 | 英商葛蘭素史克智慧財產發展有限公司 | 新穎化合物 |
| SG10201912074PA (en) | 2016-03-18 | 2020-02-27 | Immune Sensor Llc | Cyclic di-nucleotide compounds and methods of use |
| WO2017186711A1 (en) | 2016-04-25 | 2017-11-02 | Invivogen | Novel complexes of immunostimulatory compounds, and uses thereof |
| WO2018009466A1 (en) * | 2016-07-05 | 2018-01-11 | Aduro Biotech, Inc. | Locked nucleic acid cyclic dinucleotide compounds and uses thereof |
| JOP20170188A1 (ar) * | 2016-11-25 | 2019-01-30 | Janssen Biotech Inc | ثنائي النوكليوتيدات الحلقية كمنبهات ستينغ (sting) |
| CA3047394A1 (en) * | 2016-12-20 | 2018-06-28 | Merck Sharp & Dohme Corp. | Combinations of pd-1 antagonists and cyclic dinucleotide sting agonists for cancer treatment |
| WO2018118665A1 (en) * | 2016-12-20 | 2018-06-28 | Merck Sharp & Dohme Corp. | Cyclic dinucleotide sting agonists for cancer treatment |
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