CN116617420A - 靶向成纤维细胞活化蛋白α的化合物、药物组合物及用途 - Google Patents
靶向成纤维细胞活化蛋白α的化合物、药物组合物及用途 Download PDFInfo
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| PCT/US2018/057086 WO2019083990A2 (en) | 2017-10-23 | 2018-10-23 | IMAGING AND RADIATION THERAPY AGENTS TARGETING α-FIBROBLAST ACTIVATION PROTEIN α (FAP-α) |
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Families Citing this family (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116474108A (zh) | 2016-12-14 | 2023-07-25 | 普渡研究基金会 | 成纤维细胞活化蛋白(fap)-靶向成像和治疗 |
| EA202090776A1 (ru) * | 2017-10-23 | 2020-07-27 | Дзе Джонс Хопкинс Юниверсити | Визуализирующие и радиотерапевтические агенты, нацеленные на фибробласт-активирующий белок-альфа (fapalpha) |
| JP2021506972A (ja) | 2017-12-15 | 2021-02-22 | プラクシス バイオテック エルエルシー | 線維芽細胞活性化タンパク質の阻害剤 |
| SG11202007180QA (en) * | 2018-02-06 | 2020-08-28 | Univ Heidelberg | Fap inhibitor |
| US11426472B2 (en) | 2018-10-17 | 2022-08-30 | Purdue Research Foundation | Fibroblast activation protein (FAP) targeted imaging and therapy in fibrosis |
| CN113811529A (zh) | 2018-12-21 | 2021-12-17 | 普拉西斯生物技术有限责任公司 | 成纤维细胞激活蛋白抑制剂 |
| CN118406106A (zh) | 2019-07-08 | 2024-07-30 | 3B制药有限公司 | 包含成纤维细胞活化蛋白配体的化合物及其用途 |
| EP3763726A1 (en) | 2019-07-08 | 2021-01-13 | 3B Pharmaceuticals GmbH | Compounds comprising a fibroblast activation protein ligand and use thereof |
| IL289673B2 (en) | 2019-07-08 | 2026-04-01 | 3B Pharmaceuticals Gmbh | Compounds comprising a protein ligand for fibroblast activation and their use |
| WO2021055641A1 (en) * | 2019-09-17 | 2021-03-25 | Purdue Research Foundation | Fibroblast activation protein (fap)-targeted imaging and therapy of cancers and other fibrotic and inflammatory diseases |
| WO2021155292A1 (en) * | 2020-01-31 | 2021-08-05 | Philip Stewart Low | Fibroblast activation protein (fap) - targeted antifibrotic therapy |
| EP3891138B1 (en) | 2020-02-12 | 2022-01-12 | Philochem AG | Fibroblast activation protein ligands for targeted delivery applications |
| CA3176497A1 (en) | 2020-05-07 | 2021-11-11 | Fatima MECHTA-GRIGORIOU | Antxr1 as a biomarker of immunosuppressive fibroblast populations and its use for predicting response to immunotherapy |
| WO2021234181A1 (en) * | 2020-05-22 | 2021-11-25 | Universität Heidelberg | Use of fap inhibitor in a method of diagnosis |
| CN112138175A (zh) * | 2020-09-01 | 2020-12-29 | 上海市质子重离子临床技术研发中心 | 一种放射性核素99mTc标记FAPI的化合物的制备方法 |
| CN114790194B (zh) * | 2020-12-21 | 2024-03-26 | 苏州药明博锐生物科技有限公司 | 成纤维细胞活化蛋白抑制剂 |
| KR20230129261A (ko) | 2021-01-07 | 2023-09-07 | 쓰리비 파마슈티컬스 게엠베하 | 섬유모세포 활성화 단백질 리간드를 포함하는 화합물및 그의 용도 |
| EP4050018A1 (en) | 2021-01-07 | 2022-08-31 | 3B Pharmaceuticals GmbH | Compounds comprising a fibroblast activation protein ligand and use thereof |
| CN114369084B (zh) * | 2021-02-10 | 2023-02-03 | 烟台蓝纳成生物技术有限公司 | 一种截短型伊文思蓝修饰的成纤维细胞活化蛋白抑制剂及其制备方法和应用 |
| NZ803235A (en) * | 2021-02-10 | 2026-01-30 | Yantai Lannacheng Biotechnology Co Ltd | Truncated evans blue modified fibroblast activation protein inhibitor, preparation method therefor, and application thereof |
| JP2024506644A (ja) | 2021-02-12 | 2024-02-14 | フィロケム・アーゲー | 標的送達に適用するための二価線維芽細胞活性化タンパク質リガンド |
| EP4043452A1 (en) | 2021-02-12 | 2022-08-17 | Philochem AG | Bivalent fibroblast activation protein ligands for targeted delivery applications |
| CN113105432B (zh) * | 2021-03-30 | 2022-03-04 | 上海交通大学医学院附属仁济医院 | 一种碳-11(11c)放射性药物及其制备方法和应用 |
| BR112023020123A2 (pt) * | 2021-04-02 | 2024-01-23 | Univ Johns Hopkins | Agentes heterobivalentes e homobivalentes que alvejam proteína alfa de ativação de fibroblasto alfa e/ou antígeno de membrana específico da próstata |
| CN113277989B (zh) * | 2021-04-27 | 2022-05-31 | 中南大学湘雅医院 | 一种68Ga标记的分子探针、制备方法及其应用 |
| AU2022275579C1 (en) | 2021-05-19 | 2024-08-22 | Ferronova Pty Ltd | Mapping nanoparticles |
| CN113527266A (zh) * | 2021-06-23 | 2021-10-22 | 上海健康医学院 | 一种靶向fap的双氧水响应的前药及其制备方法与应用 |
| GB202109922D0 (en) | 2021-07-09 | 2021-08-25 | Blue Earth Diagnostics Ltd | Radiotracers and therapeutics binding to fibroblast activation protein (fap) |
| EP4122499A1 (en) * | 2021-07-23 | 2023-01-25 | 3B Pharmaceuticals GmbH | Fibroblast activation protein inhibitors and use thereof |
| TW202320805A (zh) * | 2021-08-18 | 2023-06-01 | 美商杜夫特學院信託管理公司 | 用於pet造影之選擇性靶向纖維母細胞活化蛋白之放射性氟標誌試劑 |
| CN113880810B (zh) * | 2021-09-24 | 2023-02-28 | 厦门大学 | 一种核素标记的配合物及其制备方法和应用 |
| MX2024004077A (es) | 2021-10-04 | 2024-04-18 | Philochem Ag | Ligandos de proteina de activacion de fibroblastos radioetiquetados. |
| TW202317541A (zh) | 2021-10-28 | 2023-05-01 | 行政院原子能委員會核能研究所 | 一種靶向成纖維細胞活化蛋白之化合物或其鹽,其製備方法及其用途 |
| WO2023081301A1 (en) * | 2021-11-05 | 2023-05-11 | On Target Laboratories, LLC | Fibroblast activation protein targeted dyes their related uses |
| US20250177582A1 (en) | 2022-01-30 | 2025-06-05 | Philochem Ag | High-affinity ligands of fibroblast activation protein for targeted delivery applications |
| JPWO2023162946A1 (https=) | 2022-02-22 | 2023-08-31 | ||
| WO2023202655A1 (en) * | 2022-04-21 | 2023-10-26 | Shanghai Sinotau Biotech. Co., Ltd | Fap inhibitors |
| WO2023222558A1 (en) | 2022-05-14 | 2023-11-23 | Zounek Alexis Nikolai | Precursor and theranostic radiotracer with improved tumor retention |
| CN115304582B (zh) * | 2022-07-20 | 2023-05-12 | 北京法伯新天医药科技有限公司 | FAP-α特异性肿瘤诊断显像剂 |
| JP2025526460A (ja) * | 2022-07-28 | 2025-08-13 | レイシオ・セラピューティクス,インコーポレーテッド | 線維芽細胞活性化タンパク質標的組成物およびその使用の方法 |
| CN115368342B (zh) * | 2022-08-24 | 2024-01-23 | 西南医科大学附属医院 | 成纤维细胞活性蛋白抑制剂、其放射性核素标记物及制备方法和应用 |
| CN119816493A (zh) | 2022-09-06 | 2025-04-11 | 菲罗化学股份公司 | 用于靶向递送应用的多价成纤维细胞激活蛋白配体 |
| EP4342890A1 (en) * | 2022-09-21 | 2024-03-27 | Erasmus University Rotterdam Medical Center | Platform and scaffold for fap targeting agents |
| TW202426433A (zh) | 2022-09-23 | 2024-07-01 | 瑞士商紐利迪姆股份公司 | 成纖維細胞活化蛋白(fap)抑制劑、fap結合物及其診斷與治療用途 |
| AU2023347470A1 (en) * | 2022-09-23 | 2025-04-10 | Nuclidium Ag | High-purity copper radiopharmaceutical compositions and diagnostic and therapeutic uses thereof |
| CN117883585A (zh) * | 2022-10-14 | 2024-04-16 | 无锡诺宇医药科技有限公司 | 靶向成纤维细胞活化蛋白的药物及其应用 |
| KR20250143347A (ko) * | 2023-02-10 | 2025-10-01 | 청두 뉴 라디오메디슨 테크놀로지 컴퍼니 리미티드 | 폴리펩타이드 화합물 및 이의 용도 |
| KR20260006628A (ko) | 2023-05-08 | 2026-01-13 | 지앙수 헨그루이 파마슈티컬스 컴퍼니 리미티드 | 섬유아세포 활성화 단백질을 표적화하는 리간드 |
| AU2024316927A1 (en) * | 2023-07-28 | 2026-02-26 | Ratio Therapeutics, Inc. | Fibroblast activation protein-targeted compositions and methods of use thereof |
| CN117164557A (zh) * | 2023-08-30 | 2023-12-05 | 上海交通大学医学院附属仁济医院 | 靶向成纤维细胞激活蛋白的放射性药物标记前体及其放射性标记化合物与应用 |
| CN121752300A (zh) | 2023-08-31 | 2026-03-27 | 荷兰拉德堡德大学学术医学中心 | 子宫内膜异位症示踪剂 |
| WO2025063849A2 (en) | 2023-09-21 | 2025-03-27 | Erasmus University Medical Center Rotterdam | Dimeric fap targeting agents |
| US20250186630A1 (en) * | 2023-12-12 | 2025-06-12 | Viewpoint Molecular Targeting, Inc. | Fibroblast activation protein targeting peptides |
| WO2025125335A1 (en) | 2023-12-13 | 2025-06-19 | Radiovaxx Gmbh | Cytotoxic or radiopharmaceutical compound with sulfur fluoride exchange group |
| WO2025125621A1 (en) | 2023-12-14 | 2025-06-19 | Radiovaxx Gmbh | Cancer-associated protein-targeted strong or covalently binding precursor compounds and radiotracers |
| WO2025146433A1 (en) | 2024-01-05 | 2025-07-10 | Radiovaxx Gmbh | Precursor and theranostic radiotracer with prolonged tumor retention |
| CN118063689B (zh) * | 2024-01-26 | 2025-01-28 | 锐康九域(厦门)医药科技有限公司 | 成纤维细胞激活蛋白-α响应水解致电荷翻转的聚合物-药物偶联物及其制备方法和应用 |
| WO2025250709A1 (en) * | 2024-05-28 | 2025-12-04 | Actithera, Inc. | Bifunctional compounds for cancer treatment |
| CN118271393B (zh) * | 2024-05-31 | 2024-09-03 | 中国药科大学 | 一种靶向fap的二聚化合物及其探针和应用 |
| WO2026007968A1 (zh) * | 2024-07-01 | 2026-01-08 | 杭州景嘉航生物医药科技有限公司 | 一种靶向结合成纤维细胞活化蛋白的化合物及应用 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1943257A2 (en) * | 2005-05-19 | 2008-07-16 | Genentech, Inc. | Fibroblast activation protein inhibitor compounds and methods |
| CA2926573C (en) | 2007-06-26 | 2018-08-28 | The Johns Hopkins University | Labeled inhibitors of prostate specific membrane antigen (psma), biological evaluation, and use as imaging agents |
| RU2494096C2 (ru) * | 2008-08-01 | 2013-09-27 | Дзе Джонс Хопкинс Юниверсити | Агенты, связывающиеся с psma, и их применение |
| WO2010036814A1 (en) * | 2008-09-25 | 2010-04-01 | Molecular Insight Pharmaceuticals, Inc. | Selective seprase inhibitors |
| WO2016149188A1 (en) * | 2015-03-13 | 2016-09-22 | The Johns Hopkins University | 68Ga-LABELED NOTA-CHELATED PSMA-TARGETED IMAGING AND THERAPEUTIC AGENTS |
| EP3222617B1 (en) * | 2009-03-19 | 2022-07-06 | The Johns Hopkins University | Psma-targeting compounds and uses thereof |
| WO2013107820A1 (en) * | 2012-01-17 | 2013-07-25 | Universiteit Antwerpen | Novel fap inhibitors |
| US20150320892A1 (en) * | 2012-06-29 | 2015-11-12 | Ge Healthcare Limited | Imaging fibrosis |
| JP6370785B2 (ja) * | 2012-08-15 | 2018-08-08 | ビセン メディカル, インコーポレイテッド | 前立腺がんイメージングのための前立腺特異的抗原薬剤およびその使用方法 |
| EP3102242A2 (en) * | 2014-02-03 | 2016-12-14 | Philochem AG | Targeted drug conjugates |
| US10736974B2 (en) | 2014-10-22 | 2020-08-11 | The Johns Hopkins University | Scaffolds and multifunctional intermediates for imaging PSMA and cancer therapy |
| WO2016196628A1 (en) * | 2015-06-01 | 2016-12-08 | The Johns Hopkins University | Nuclear imaging and radiotherapeutics agents targeting carbonic anhydrase ix and uses thereof |
| CN116474108A (zh) | 2016-12-14 | 2023-07-25 | 普渡研究基金会 | 成纤维细胞活化蛋白(fap)-靶向成像和治疗 |
| EA202090776A1 (ru) * | 2017-10-23 | 2020-07-27 | Дзе Джонс Хопкинс Юниверсити | Визуализирующие и радиотерапевтические агенты, нацеленные на фибробласт-активирующий белок-альфа (fapalpha) |
| SG11202007180QA (en) | 2018-02-06 | 2020-08-28 | Univ Heidelberg | Fap inhibitor |
-
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- 2018-10-23 AU AU2018355222A patent/AU2018355222B2/en active Active
- 2018-10-23 BR BR112020008011-0A patent/BR112020008011A2/pt unknown
-
2020
- 2020-04-20 IL IL274088A patent/IL274088A/en unknown
- 2020-07-13 MX MX2023013164A patent/MX2023013164A/es unknown
-
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- 2023-07-18 US US18/354,282 patent/US11938201B2/en active Active
-
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-
2025
- 2025-04-07 US US19/172,114 patent/US20250235565A1/en active Pending
Non-Patent Citations (2)
| Title |
|---|
| PETRA DVOŘÁKOVÁ等: "Inhibitor-Decorated Polymer Conjugates Targeting Fibroblast Activation Protein", 《JOURNAL OF MEDICINAL CHEMISTRY》, vol. 60, no. 20, 27 September 2017 (2017-09-27), pages 8385 - 8393, XP055615512, DOI: 10.1021/acs.jmedchem.7b00767 * |
| 王吉欣等: "《放射性药物学》", vol. 1, 31 May 1999, 原子能出版社, pages: 357 * |
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| US12115233B2 (en) | 2024-10-15 |
| MX2020004807A (es) | 2020-10-05 |
| KR20240162157A (ko) | 2024-11-14 |
| JP2024109682A (ja) | 2024-08-14 |
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