RU2705204C2 - Лечение злокачественных опухолей с использованием модуляторов изоформ piз-киназы - Google Patents
Лечение злокачественных опухолей с использованием модуляторов изоформ piз-киназы Download PDFInfo
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- RU2705204C2 RU2705204C2 RU2015156069A RU2015156069A RU2705204C2 RU 2705204 C2 RU2705204 C2 RU 2705204C2 RU 2015156069 A RU2015156069 A RU 2015156069A RU 2015156069 A RU2015156069 A RU 2015156069A RU 2705204 C2 RU2705204 C2 RU 2705204C2
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| TWI546305B (zh) | 2011-01-10 | 2016-08-21 | 英菲尼提製藥股份有限公司 | 製備異喹啉酮之方法及異喹啉酮之固體形式 |
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| EA201492082A1 (ru) | 2012-06-04 | 2015-03-31 | Фармасайкликс, Инк. | Кристаллические формы ингибитора тирозинкиназы брутона |
| US8828998B2 (en) | 2012-06-25 | 2014-09-09 | Infinity Pharmaceuticals, Inc. | Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors |
| KR20150032340A (ko) | 2012-07-24 | 2015-03-25 | 파마시클릭스, 인코포레이티드 | 브루톤 티로신 키나제(btk)의 억제제에 대한 내성과 관련된 돌연변이 |
| CN105102000B (zh) | 2012-11-01 | 2021-10-22 | 无限药品公司 | 使用pi3激酶亚型调节剂的癌症疗法 |
| MA38183A1 (fr) | 2012-11-15 | 2017-03-31 | Pharmacyclics Inc | Composés pyrrolopyrimidines en tant qu'inhibiteurs de kinase |
| WO2014144326A1 (en) | 2013-03-15 | 2014-09-18 | G1 Therapeutics, Inc. | Transient protection of normal cells during chemotherapy |
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| KR20220165809A (ko) | 2013-12-06 | 2022-12-15 | 에피자임, 인코포레이티드 | 암 치료를 위한 병용 요법 |
| WO2015116729A2 (en) * | 2014-01-28 | 2015-08-06 | Emergent Product Development Seattle, Llc | Anti-cd37 antibody and anti-cd20 antibody combination therapy for treatment of b-cell malignancies and disorders |
| GB201402431D0 (en) | 2014-02-12 | 2014-03-26 | Karus Therapeutics Ltd | Compounds |
| JP2017509336A (ja) * | 2014-03-20 | 2017-04-06 | ファーマサイクリックス エルエルシー | ホスホリパーゼcガンマ2及び耐性に関連した変異 |
| ES2806506T3 (es) | 2014-03-25 | 2021-02-17 | Ono Pharmaceutical Co | Agente profiláctico y/o agente terapéutico para el linfoma difuso de células B grandes |
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| PL3157527T3 (pl) * | 2014-06-17 | 2023-08-07 | Epizyme, Inc. | Inhibitory ezh2 do leczenia chłoniaka |
| CA2959602A1 (en) | 2014-08-01 | 2016-02-04 | Pharmacyclics Llc | Inhibitors of bruton's tyrosine kinase |
| EP3193877A4 (en) | 2014-08-07 | 2018-04-04 | Pharmacyclics LLC | Novel formulations of a bruton's tyrosine kinase inhibitor |
| TW201618772A (zh) * | 2014-08-11 | 2016-06-01 | 艾森塔製藥公司 | Btk抑制劑、pi3k抑制劑、jak-2抑制劑及/或bcl-2抑制劑之治療組合物 |
| WO2016040858A1 (en) * | 2014-09-12 | 2016-03-17 | G1 Therapeutics, Inc. | Combinations and dosing regimes to treat rb-positive tumors |
| WO2016054491A1 (en) | 2014-10-03 | 2016-04-07 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| IL315294A (en) | 2015-03-03 | 2024-10-01 | Pharmacyclics Llc | Pharmaceutical formulations of bruton's tyrosine kinase inhibitor |
| EP3281943B1 (en) | 2015-04-09 | 2023-06-28 | ONO Pharmaceutical Co., Ltd. | Process for producing purinone derivative |
| KR20170134462A (ko) | 2015-04-13 | 2017-12-06 | 다이이찌 산쿄 가부시키가이샤 | Mdm2 저해제와 btk 저해제의 병용 치료법 |
| UY36660A (es) * | 2015-04-30 | 2016-11-30 | Bayer Pharma AG | Combinaciones de inhibidores de irak4 |
| JP6890097B2 (ja) | 2015-06-10 | 2021-06-18 | エピザイム,インコーポレイティド | リンパ腫を処置するためのezh2阻害剤 |
| EP3313405A1 (en) * | 2015-06-23 | 2018-05-02 | Gilead Sciences, Inc. | Combination therapies for treating b-cell malignancies |
| JP6815383B2 (ja) * | 2015-08-03 | 2021-01-20 | ギリアード サイエンシーズ, インコーポレイテッド | がん処置のための組み合わせ療法 |
| GB201514758D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Formulation |
| GB201514760D0 (en) * | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compounds and method of use |
| GB201514754D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compounds |
| JP2018527396A (ja) * | 2015-09-21 | 2018-09-20 | イフォム・フォンダツィオーネ・イスティトゥート・フィルチ・ディ・オンコロジア・モレコラーレ | 血液癌に対する新規治療戦略 |
| WO2017062823A1 (en) * | 2015-10-08 | 2017-04-13 | The Wistar Institute Of Anatomy And Biology | Therapeutic cancer treatments based on tp53 gene mutations |
| CN108137592B (zh) * | 2015-11-03 | 2021-03-05 | 纽弗姆制药有限公司 | 用于治疗血癌的氘代化合物以及其组合物和方法 |
| CN108699061B (zh) * | 2015-11-16 | 2022-07-05 | 纽弗姆制药有限公司 | 用于治疗血液恶性肿瘤、炎症和自身免疫性疾病的氘代化合物 |
| EP3474856B1 (en) | 2016-06-24 | 2022-09-14 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| CA3044691A1 (en) | 2016-10-26 | 2018-05-03 | Genea Biocells USA (Holdings), Inc. | Improved generation of muscle lineage cells and therapeutic uses thereof |
| CA3043030A1 (en) | 2016-11-10 | 2018-05-17 | Jose Baselga BASELGA | Inhibition of kmt2d for the treatment of cancer |
| JP6730525B2 (ja) | 2016-11-21 | 2020-07-29 | ナノストリング テクノロジーズ,インコーポレイティド | 化学組成物とそれを利用する方法 |
| MX394882B (es) * | 2016-12-07 | 2025-03-24 | Beigene Ltd | Derivados de imidazo[1,5-a]pirazina como inhibidores de fosfatidilinositol-4,5-bisfosfato 3-quinasadelta (pi3kdelta) |
| AU2018246257B2 (en) * | 2017-03-30 | 2022-05-12 | Merck Patent Gmbh | Solid form of (S)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxy-pyridazin-3-yl)methanol |
| BR112020004500A2 (pt) | 2017-09-08 | 2020-12-01 | Beigene, Ltd. | derivados de imidazo [1,5-a] pirazina como inibidores de pi3kdelta |
| EP3794146B1 (en) | 2018-05-14 | 2025-12-10 | Bruker Spatial Biology, Inc. | Method for identifying a predetermined nucleotide sequence |
| MX2021006368A (es) * | 2018-11-30 | 2021-10-13 | Janssen Biotech Inc | Métodos para tratar el linfoma folicular. |
| CN112143700B (zh) * | 2019-06-26 | 2024-07-19 | 上海细胞治疗集团股份有限公司 | 制备过表达外源基因的免疫效应细胞的方法 |
| JP2022553820A (ja) | 2019-11-05 | 2022-12-26 | アッヴィ・インコーポレイテッド | 骨髄線維症及びmpn関連障害をナビトクラクスで処置する際に使用するための投与レジメン |
| AU2021292490A1 (en) * | 2020-06-15 | 2023-02-09 | Metabolic Technologies, LLC | Compositions and methods of use of beta-hydroxy-beta-methylbutyrate (HMB) and chemotherapy agents |
| US11648255B2 (en) * | 2020-07-06 | 2023-05-16 | Masarykova Univerzita | Inhibitors for treatment of hematological malignancies |
| WO2022019920A1 (en) * | 2020-07-24 | 2022-01-27 | Verastem, Inc. | Treatment of cancers using pi3 kinase isoform modulators |
| WO2023275330A1 (en) * | 2021-06-30 | 2023-01-05 | Janssen Pharmaceutica Nv | Treatments for diffuse large b-cell lymphoma |
| WO2024086789A2 (en) * | 2022-10-20 | 2024-04-25 | Prelude Therapeutics Incorporated | Mutant pi3k-alpha inhibitors and their use as pharmaceuticals |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120183535A1 (en) * | 2010-06-03 | 2012-07-19 | Pharmacyclics, Inc. | use of inhibitors of bruton's tyrosine kinase (btk) |
| WO2013059738A2 (en) * | 2011-10-19 | 2013-04-25 | Pharmacyclics, Inc. | Use of inhibitors of bruton's tyrosine kinase (btk) |
Family Cites Families (172)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3536809A (en) | 1969-02-17 | 1970-10-27 | Alza Corp | Medication method |
| US3598123A (en) | 1969-04-01 | 1971-08-10 | Alza Corp | Bandage for administering drugs |
| US3845770A (en) | 1972-06-05 | 1974-11-05 | Alza Corp | Osmatic dispensing device for releasing beneficial agent |
| US3916899A (en) | 1973-04-25 | 1975-11-04 | Alza Corp | Osmotic dispensing device with maximum and minimum sizes for the passageway |
| US4008719A (en) | 1976-02-02 | 1977-02-22 | Alza Corporation | Osmotic system having laminar arrangement for programming delivery of active agent |
| US4270537A (en) | 1979-11-19 | 1981-06-02 | Romaine Richard A | Automatic hypodermic syringe |
| KR890002631B1 (ko) | 1984-10-04 | 1989-07-21 | 몬산토 캄파니 | 생물학적으로 활성인 소마토트로핀을 지속적으로 유리하는 조성물 |
| IE58110B1 (en) | 1984-10-30 | 1993-07-14 | Elan Corp Plc | Controlled release powder and process for its preparation |
| US4596556A (en) | 1985-03-25 | 1986-06-24 | Bioject, Inc. | Hypodermic injection apparatus |
| US5023252A (en) | 1985-12-04 | 1991-06-11 | Conrex Pharmaceutical Corporation | Transdermal and trans-membrane delivery of drugs |
| US4886499A (en) | 1986-12-18 | 1989-12-12 | Hoffmann-La Roche Inc. | Portable injection appliance |
| GB8704027D0 (en) | 1987-02-20 | 1987-03-25 | Owen Mumford Ltd | Syringe needle combination |
| US5001139A (en) | 1987-06-12 | 1991-03-19 | American Cyanamid Company | Enchancers for the transdermal flux of nivadipine |
| US4992445A (en) | 1987-06-12 | 1991-02-12 | American Cyanamid Co. | Transdermal delivery of pharmaceuticals |
| US4941880A (en) | 1987-06-19 | 1990-07-17 | Bioject, Inc. | Pre-filled ampule and non-invasive hypodermic injection device assembly |
| US4940460A (en) | 1987-06-19 | 1990-07-10 | Bioject, Inc. | Patient-fillable and non-invasive hypodermic injection device assembly |
| US4790824A (en) | 1987-06-19 | 1988-12-13 | Bioject, Inc. | Non-invasive hypodermic injection device |
| US5339163A (en) | 1988-03-16 | 1994-08-16 | Canon Kabushiki Kaisha | Automatic exposure control device using plural image plane detection areas |
| US5073543A (en) | 1988-07-21 | 1991-12-17 | G. D. Searle & Co. | Controlled release formulations of trophic factors in ganglioside-lipsome vehicle |
| FR2638359A1 (fr) | 1988-11-03 | 1990-05-04 | Tino Dalto | Guide de seringue avec reglage de la profondeur de penetration de l'aiguille dans la peau |
| GB8827305D0 (en) | 1988-11-23 | 1988-12-29 | British Bio Technology | Compounds |
| IT1229203B (it) | 1989-03-22 | 1991-07-25 | Bioresearch Spa | Impiego di acido 5 metiltetraidrofolico, di acido 5 formiltetraidrofolico e dei loro sali farmaceuticamente accettabili per la preparazione di composizioni farmaceutiche in forma a rilascio controllato attive nella terapia dei disturbi mentali organici e composizioni farmaceutiche relative. |
| PH30995A (en) | 1989-07-07 | 1997-12-23 | Novartis Inc | Sustained release formulations of water soluble peptides. |
| US5120548A (en) | 1989-11-07 | 1992-06-09 | Merck & Co., Inc. | Swelling modulated polymeric drug delivery device |
| US5312335A (en) | 1989-11-09 | 1994-05-17 | Bioject Inc. | Needleless hypodermic injection device |
| US5064413A (en) | 1989-11-09 | 1991-11-12 | Bioject, Inc. | Needleless hypodermic injection device |
| US5733566A (en) | 1990-05-15 | 1998-03-31 | Alkermes Controlled Therapeutics Inc. Ii | Controlled release of antiparasitic agents in animals |
| US5190521A (en) | 1990-08-22 | 1993-03-02 | Tecnol Medical Products, Inc. | Apparatus and method for raising a skin wheal and anesthetizing skin |
| US5527288A (en) | 1990-12-13 | 1996-06-18 | Elan Medical Technologies Limited | Intradermal drug delivery device and method for intradermal delivery of drugs |
| GB9118204D0 (en) | 1991-08-23 | 1991-10-09 | Weston Terence E | Needle-less injector |
| SE9102652D0 (sv) | 1991-09-13 | 1991-09-13 | Kabi Pharmacia Ab | Injection needle arrangement |
| US5580578A (en) | 1992-01-27 | 1996-12-03 | Euro-Celtique, S.A. | Controlled release formulations coated with aqueous dispersions of acrylic polymers |
| US5328483A (en) | 1992-02-27 | 1994-07-12 | Jacoby Richard M | Intradermal injection device with medication and needle guard |
| JP3645903B2 (ja) | 1992-03-04 | 2005-05-11 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 比較ゲノムハイブリダイゼーション(cgh) |
| US5383851A (en) | 1992-07-24 | 1995-01-24 | Bioject Inc. | Needleless hypodermic injection device |
| US5569189A (en) | 1992-09-28 | 1996-10-29 | Equidyne Systems, Inc. | hypodermic jet injector |
| US5334144A (en) | 1992-10-30 | 1994-08-02 | Becton, Dickinson And Company | Single use disposable needleless injector |
| TW333456B (en) | 1992-12-07 | 1998-06-11 | Takeda Pharm Ind Co Ltd | A pharmaceutical composition of sustained-release preparation the invention relates to a pharmaceutical composition of sustained-release preparation which comprises a physiologically active peptide. |
| US5455258A (en) | 1993-01-06 | 1995-10-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
| US5591767A (en) | 1993-01-25 | 1997-01-07 | Pharmetrix Corporation | Liquid reservoir transdermal patch for the administration of ketorolac |
| US6087324A (en) | 1993-06-24 | 2000-07-11 | Takeda Chemical Industries, Ltd. | Sustained-release preparation |
| WO1995024176A1 (en) | 1994-03-07 | 1995-09-14 | Bioject, Inc. | Ampule filling device |
| US5466220A (en) | 1994-03-08 | 1995-11-14 | Bioject, Inc. | Drug vial mixing and transfer device |
| IT1270594B (it) | 1994-07-07 | 1997-05-07 | Recordati Chem Pharm | Composizione farmaceutica a rilascio controllato di moguisteina in sospensione liquida |
| US5599302A (en) | 1995-01-09 | 1997-02-04 | Medi-Ject Corporation | Medical injection system and method, gas spring thereof and launching device using gas spring |
| US5863949A (en) | 1995-03-08 | 1999-01-26 | Pfizer Inc | Arylsulfonylamino hydroxamic acid derivatives |
| CA2218503C (en) | 1995-04-20 | 2001-07-24 | Pfizer Inc. | Arylsulfonyl hydroxamic acid derivatives |
| US5730723A (en) | 1995-10-10 | 1998-03-24 | Visionary Medical Products Corporation, Inc. | Gas pressured needle-less injection device and method |
| DE69632684T2 (de) | 1995-06-27 | 2005-06-09 | Takeda Pharmaceutical Co. Ltd. | Verfahren zur herstellung von zubereitungen mit verzögerter freisetzung |
| TW448055B (en) | 1995-09-04 | 2001-08-01 | Takeda Chemical Industries Ltd | Method of production of sustained-release preparation |
| JP2909418B2 (ja) | 1995-09-18 | 1999-06-23 | 株式会社資生堂 | 薬物の遅延放出型マイクロスフイア |
| EP0780386B1 (en) | 1995-12-20 | 2002-10-02 | F. Hoffmann-La Roche Ag | Matrix metalloprotease inhibitors |
| US5893397A (en) | 1996-01-12 | 1999-04-13 | Bioject Inc. | Medication vial/syringe liquid-transfer apparatus |
| US5980945A (en) | 1996-01-16 | 1999-11-09 | Societe De Conseils De Recherches Et D'applications Scientifique S.A. | Sustained release drug formulations |
| GB9607549D0 (en) | 1996-04-11 | 1996-06-12 | Weston Medical Ltd | Spring-powered dispensing device |
| US6264970B1 (en) | 1996-06-26 | 2001-07-24 | Takeda Chemical Industries, Ltd. | Sustained-release preparation |
| JP3195756B2 (ja) | 1996-07-04 | 2001-08-06 | 公子 吉水 | 潤滑補助体 |
| KR20000067904A (ko) | 1996-07-18 | 2000-11-25 | 디. 제이. 우드, 스피겔 알렌 제이 | 매트릭스 메탈로프로테아제의 포스피네이트계 억제제 |
| BR9711223A (pt) | 1996-08-23 | 1999-08-17 | Pfizer | Derivados de cido arilsulfonilamino-hidrox mico |
| US6419961B1 (en) | 1996-08-29 | 2002-07-16 | Takeda Chemical Industries, Ltd. | Sustained release microcapsules of a bioactive substance and a biodegradable polymer |
| CA2217134A1 (en) | 1996-10-09 | 1998-04-09 | Sumitomo Pharmaceuticals Co., Ltd. | Sustained release formulation |
| EP0839525B1 (en) | 1996-10-31 | 2004-08-04 | Takeda Chemical Industries, Ltd. | Sustained-release preparation |
| DK0946169T3 (da) | 1996-12-20 | 2003-04-22 | Takeda Chemical Industries Ltd | Fremgangsmåde til fremstilling af et præparat med vedvarende frigivelse |
| EP0950059B1 (en) | 1997-01-06 | 2004-08-04 | Pfizer Inc. | Cyclic sulfone derivatives |
| US5891474A (en) | 1997-01-29 | 1999-04-06 | Poli Industria Chimica, S.P.A. | Time-specific controlled release dosage formulations and method of preparing same |
| IL131042A0 (en) | 1997-02-03 | 2001-01-28 | Pfizer Prod Inc | Arylsulfonylamino hydroxamic acid derivatives |
| BR9807824A (pt) | 1997-02-07 | 2000-03-08 | Pfizer | Derivados de n-hidróxi-beta-sulfonil-propionamida e seu uso como inibidores de metaloproteinases de matriz |
| KR20000070923A (ko) | 1997-02-11 | 2000-11-25 | 디. 제이. 우드, 스피겔 알렌 제이 | 아릴설포닐 하이드록삼산 유도체 |
| US5993412A (en) | 1997-05-19 | 1999-11-30 | Bioject, Inc. | Injection apparatus |
| GB9725782D0 (en) | 1997-12-05 | 1998-02-04 | Pfizer Ltd | Therapeutic agents |
| IT1298087B1 (it) | 1998-01-08 | 1999-12-20 | Fiderm S R L | Dispositivo per il controllo della profondita' di penetrazione di un ago, in particolare applicabile ad una siringa per iniezioni |
| GB9801690D0 (en) | 1998-01-27 | 1998-03-25 | Pfizer Ltd | Therapeutic agents |
| US6613358B2 (en) | 1998-03-18 | 2003-09-02 | Theodore W. Randolph | Sustained-release composition including amorphous polymer |
| US6432970B2 (en) | 1998-04-09 | 2002-08-13 | Johns Hopkins University School Of Medicine | Inhibitors of hedgehog signaling pathways, compositions and uses related thereto |
| US7098196B1 (en) | 1999-10-13 | 2006-08-29 | Johns Hopkins University School Of Medicine | Regulators of the hedgehog pathway, compositions and uses related thereto |
| PA8469401A1 (es) | 1998-04-10 | 2000-05-24 | Pfizer Prod Inc | Derivados biciclicos del acido hidroxamico |
| PA8469501A1 (es) | 1998-04-10 | 2000-09-29 | Pfizer Prod Inc | Hidroxamidas del acido (4-arilsulfonilamino)-tetrahidropiran-4-carboxilico |
| KR19990085365A (ko) | 1998-05-16 | 1999-12-06 | 허영섭 | 지속적으로 약물 조절방출이 가능한 생분해성 고분자 미립구 및그 제조방법 |
| US6927024B2 (en) | 1998-11-30 | 2005-08-09 | Genentech, Inc. | PCR assay |
| US6248363B1 (en) | 1999-11-23 | 2001-06-19 | Lipocine, Inc. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
| WO2001019800A2 (en) | 1999-09-16 | 2001-03-22 | Curis, Inc. | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
| US20070021493A1 (en) | 1999-09-16 | 2007-01-25 | Curis, Inc. | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
| AU780612C (en) | 1999-10-14 | 2005-10-20 | Curis, Inc. | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
| WO2001042507A1 (en) | 1999-12-09 | 2001-06-14 | Advanced Research & Technology Institute | Fluorescent in situ rt-pcr |
| IL133809A0 (en) | 1999-12-30 | 2001-04-30 | Yeda Res & Dev | Steroidal alkaloids and pharmaceutical compositions comprising them |
| DE60113823T3 (de) | 2000-03-30 | 2010-07-01 | Curis, Inc., Cambridge | Kleine organische moleküle als regulatoren der zellproliferation |
| CA2439402A1 (en) | 2001-03-02 | 2002-09-12 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Pcr method |
| EA007339B1 (ru) | 2001-07-27 | 2006-08-25 | Кьюэрис, Инк. | Медиаторы путей передачи сигналов генами hedgehog, содержащие их композиции и способы применения указанных веществ |
| ATE511840T1 (de) | 2001-10-09 | 2011-06-15 | Amgen Inc | Imidazolderivate als entzündungshemmende mittel |
| US20030113828A1 (en) | 2001-11-09 | 2003-06-19 | Ginsberg Mark H. | Compositions and methods for modulating Syk function |
| US20030158195A1 (en) | 2001-12-21 | 2003-08-21 | Cywin Charles L. | 1,6 naphthyridines useful as inhibitors of SYK kinase |
| ATE404200T1 (de) | 2002-04-22 | 2008-08-15 | Univ Johns Hopkins Med | Modulatoren von hedgehog signalpfaden, zusammensetzungen und verwandte verwendungen |
| AU2003265853A1 (en) | 2002-08-29 | 2004-03-19 | Curis, Inc. | Hedgehog antagonists, methods and uses related thereto |
| US7199119B2 (en) | 2002-10-31 | 2007-04-03 | Amgen Inc. | Antiinflammation agents |
| FR2850022B1 (fr) | 2003-01-22 | 2006-09-08 | Centre Nat Rech Scient | Nouvelle utilisation de la mifepristone et de ses derives comme modulateurs de la voie de signalisation des proteines hedgehog et ses applications |
| EP2371835A1 (en) | 2003-07-03 | 2011-10-05 | The Trustees Of The University Of Pennsylvania | Inhibition of syk kinase expression |
| WO2005013800A2 (en) | 2003-07-15 | 2005-02-17 | The Johns Hopkins University | Elevated hedgehog pathway activity in digestive system tumors, and methods of treating digestive system tumors having elevated hedgehog pathway activity |
| WO2005016348A1 (en) | 2003-08-14 | 2005-02-24 | Icos Corporation | Method of inhibiting immune responses stimulated by an endogenous factor |
| GB0321710D0 (en) | 2003-09-16 | 2003-10-15 | Novartis Ag | Organic compounds |
| WO2005033288A2 (en) | 2003-09-29 | 2005-04-14 | The Johns Hopkins University | Hedgehog pathway antagonists |
| WO2005032343A2 (en) | 2003-10-01 | 2005-04-14 | The Johns Hopkins University | Hedgehog signaling in prostate regeneration neoplasia and metastasis |
| WO2005042700A2 (en) | 2003-10-20 | 2005-05-12 | The Johns Hopkins University | Use of hedgehog pathway inhibitors in small-cell lung cancer |
| CA2546074A1 (en) | 2003-11-14 | 2005-06-02 | Yale University | Syk-targeted nucleic acid interference |
| US7122799B2 (en) | 2003-12-18 | 2006-10-17 | Palo Alto Research Center Incorporated | LED or laser enabled real-time PCR system and spectrophotometer |
| US8057815B2 (en) | 2004-04-19 | 2011-11-15 | Portola Pharmaceuticals, Inc. | Methods of treatment with Syk inhibitors |
| WO2006078283A2 (en) | 2004-04-30 | 2006-07-27 | Genentech, Inc. | Quinoxaline inhibitors of hedgehog signalling |
| WO2005113556A1 (en) | 2004-05-13 | 2005-12-01 | Icos Corporation | Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta |
| BRPI0514444A (pt) | 2004-08-27 | 2008-06-10 | Infinity Pharmaceuticals Inc | análogos de ciclopamina e métodos de uso destes |
| KR20160058972A (ko) | 2004-09-02 | 2016-05-25 | 제넨테크, 인크. | 헤지호그 신호전달에 대한 피리딜 억제제 |
| CN101083996A (zh) | 2004-10-28 | 2007-12-05 | Irm责任有限公司 | 作为hedgehog途径调节剂的化合物和组合物 |
| AU2006219231B2 (en) | 2005-02-28 | 2010-01-14 | Japan Tobacco Inc. | Novel aminopyridine compound with Syk inhibitory activity |
| US20090156611A1 (en) | 2005-11-11 | 2009-06-18 | Licentia Ltd. | Mammalian hedgehog signaling modulators |
| JP5225857B2 (ja) | 2005-11-14 | 2013-07-03 | ジェネンテック,インコーポレイティド | ヘッジホッグシグナル伝達のビスアミド阻害剤 |
| CA2645583A1 (en) | 2006-03-20 | 2007-09-27 | F. Hoffman-La Roche Ag | Methods of inhibiting btk and syk protein kinases |
| EP2010170A2 (en) | 2006-04-14 | 2009-01-07 | Novartis AG | Use of biarylcarboxamides in the treatment of hedgehog pathway-related disorders |
| UA93548C2 (uk) | 2006-05-05 | 2011-02-25 | Айерем Елелсі | Сполуки та композиції як модулятори хеджхогівського сигнального шляху |
| JP5225264B2 (ja) | 2006-05-09 | 2013-07-03 | ノベアメド・リミテッド | 細胞増殖障害の処置 |
| US20110021513A1 (en) | 2006-09-07 | 2011-01-27 | Biogen Idec Ma Inc. | Modulators of interleukin-1 receptor-associated kinase |
| MY181496A (en) | 2006-10-31 | 2020-12-23 | Government Of The United States Of America Represented By The Sec Dep Of Health And Human Services | Smoothened polypeptides and methods of use |
| BRPI0720546A2 (pt) | 2006-12-14 | 2015-06-23 | Daiichi Sankyo Co Ltd | Composto, inibidor, medicamento, agente antitumor, composição farmacêutica, método para tratar câncer, e, uso do composto |
| TWI433674B (zh) | 2006-12-28 | 2014-04-11 | Infinity Discovery Inc | 環杷明(cyclopamine)類似物類 |
| NZ579361A (en) | 2007-03-07 | 2012-04-27 | Infinity Discovery Inc | Heterocyclic cyclopamine analogs and methods of use thereof |
| US7964590B2 (en) | 2007-03-07 | 2011-06-21 | Infinity Discovery, Inc. | Cyclopamine lactam analogs and methods of use thereof |
| BRPI0808772A2 (pt) | 2007-03-14 | 2014-08-12 | Exelixis Inc | Inibidores da via de hedgehog |
| PE20090188A1 (es) | 2007-03-15 | 2009-03-20 | Novartis Ag | Compuestos heterociclicos como moduladores de la senda de hedgehog |
| WO2008131354A2 (en) | 2007-04-20 | 2008-10-30 | The Curators Of The University Of Missouri | Phytoestrogens as regulators of hedgehog signaling and methods of their use in cancer treatment |
| WO2009006577A2 (en) | 2007-07-03 | 2009-01-08 | The Regents Of The University Of Michigan | Compositions and methods for inhibiting ezh2 |
| CN101896472A (zh) | 2007-12-13 | 2010-11-24 | 锡耶纳生物技术股份公司 | Hedgehog途径拮抗剂及其治疗应用 |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| MX358640B (es) | 2008-01-04 | 2018-08-29 | Intellikine Llc | Isoquinolin-1 (2h) -onas y tieno [2,3-d]pirimidin-4(3h) -onas substituidas, y metodos de uso de las mismas. |
| KR20100103455A (ko) | 2008-01-10 | 2010-09-27 | 아사히 가라스 가부시키가이샤 | 유리, 발광 장치용 피복재 및 발광 장치 |
| WO2009089598A2 (en) | 2008-01-18 | 2009-07-23 | Katholieke Universiteit Leuven | Msmb-gene methylation based diagnosis, staging and prognosis of prostate cancer |
| JP5547099B2 (ja) | 2008-03-14 | 2014-07-09 | インテリカイン, エルエルシー | キナーゼ阻害剤および使用方法 |
| FR2929851B1 (fr) | 2008-04-09 | 2012-11-30 | Centre Nat Rech Scient | Molecules inhibant une voie metabolique impliquant la proteine tyrosine kinase syk et procede d'identification de ces molecules |
| PT2323993E (pt) | 2008-04-16 | 2015-10-12 | Portola Pharm Inc | 2,6-diamino-pirimidina-5-il-carboxamidas como inibidores de quinasses syk ou jak |
| US9096611B2 (en) | 2008-07-08 | 2015-08-04 | Intellikine Llc | Kinase inhibitors and methods of use |
| US8703778B2 (en) | 2008-09-26 | 2014-04-22 | Intellikine Llc | Heterocyclic kinase inhibitors |
| US9107942B2 (en) | 2008-10-31 | 2015-08-18 | University Of Rochester | Methods of diagnosing and treating fibrosis |
| JP5794919B2 (ja) * | 2008-11-13 | 2015-10-14 | ギリアード カリストガ エルエルシー | 血液学的な悪性疾患のための療法 |
| US8450321B2 (en) | 2008-12-08 | 2013-05-28 | Gilead Connecticut, Inc. | 6-(1H-indazol-6-yl)-N-[4-(morpholin-4-yl)phenyl]imidazo-[1,2-A]pyrazin-8-amine, or a pharmaceutically acceptable salt thereof, as a SYK inhibitor |
| MX2011006094A (es) | 2008-12-08 | 2011-11-29 | Gilead Connecticut Inc | Inhibidores de imidazopirazina syk. |
| CA2749403A1 (en) | 2009-01-13 | 2010-09-02 | Glaxo Group Limited | Pyrimidinecarboxamide derivatives as inhibitors of syk kinase |
| KR20120046099A (ko) | 2009-02-04 | 2012-05-09 | 유니버시티 오브 조지아 리서치 파운데이션 인코퍼레이티드 | 섬유화를 억제하고 섬유화 질병을 치료하는 방법 |
| EP2451811A1 (en) | 2009-05-27 | 2012-05-16 | F. Hoffmann-La Roche AG | Bicyclic indole-pyrimidine pi3k inhibitor compounds selective for p110 delta, and methods of use |
| CA2761445A1 (en) | 2009-05-27 | 2010-12-02 | Genentech, Inc. | Bicyclic pyrimidine pi3k inhibitor compounds selective for p110 delta, and methods of use |
| EP2443123B1 (en) | 2009-06-15 | 2017-04-05 | Rigel Pharmaceuticals, Inc. | Small molecule inhibitors of spleen tyrosine kinase (syk) |
| JP2013501002A (ja) | 2009-07-30 | 2013-01-10 | アイアールエム・リミテッド・ライアビリティ・カンパニー | Sykキナーゼ阻害剤としての化合物および組成物 |
| TW201105669A (en) | 2009-07-30 | 2011-02-16 | Irm Llc | Compounds and compositions as Syk kinase inhibitors |
| CA2775942A1 (en) | 2009-09-29 | 2011-04-07 | Xcovery Holding Company Llc | Pi3k (delta) selective inhibitors |
| WO2011075560A1 (en) | 2009-12-17 | 2011-06-23 | Merck Sharp & Dohme Corp. | Aminopyrimidines as syk inhibitors |
| MA33926B1 (fr) | 2009-12-17 | 2013-01-02 | Merck Sharp & Dohme | Aminopyrimidines en tant qu'inhibiteurs de la syk |
| KR101790255B1 (ko) | 2009-12-23 | 2017-10-26 | 다케다 야쿠힌 고교 가부시키가이샤 | Syk 억제제로서의 융합된 헤테로방향족 피롤리디논 |
| US20110251216A1 (en) | 2010-02-19 | 2011-10-13 | The Regents Of The University Of Michigan | Compositions and methods for inhibiting ezh2 |
| GB201007203D0 (en) | 2010-04-29 | 2010-06-16 | Glaxo Group Ltd | Novel compounds |
| EP2571357B1 (en) | 2010-05-21 | 2016-07-06 | Infinity Pharmaceuticals, Inc. | Chemical compounds, compositions and methods for kinase modulation |
| US20110306622A1 (en) * | 2010-06-11 | 2011-12-15 | Calitoga Pharmaceuticals, Inc. | Methods of treating hematological disorders with quinazolinone compounds in selected subjects |
| US20130195843A1 (en) | 2010-06-23 | 2013-08-01 | British Columbia Cancer Agency Branch | Biomarkers for Non-Hodgkin Lymphomas and Uses Thereof |
| PL2614369T3 (pl) | 2010-09-10 | 2016-08-31 | Epizyme Inc | Sposób określania przydatności inhibitorów ludzkiego ezh2 w leczeniu |
| US9175331B2 (en) | 2010-09-10 | 2015-11-03 | Epizyme, Inc. | Inhibitors of human EZH2, and methods of use thereof |
| CA2816219C (en) | 2010-11-01 | 2019-10-29 | Portola Pharmaceuticals, Inc. | Nicotinamides as syk modulators |
| TWI546305B (zh) | 2011-01-10 | 2016-08-21 | 英菲尼提製藥股份有限公司 | 製備異喹啉酮之方法及異喹啉酮之固體形式 |
| US20130004481A1 (en) * | 2011-01-12 | 2013-01-03 | Boehringer Ingelheim International Gmbh | Anticancer therapy |
| KR20140025500A (ko) | 2011-05-04 | 2014-03-04 | 머크 샤프 앤드 돔 코포레이션 | 아미노-피리딘-함유 비장 티로신 키나제 (Syk) 억제제 |
| EP3495368B1 (en) * | 2011-07-19 | 2023-05-31 | Merck Sharp & Dohme B.V. | (s)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-2-methoxy-n-(pyridin-2-yl)benzamide as btk-inhibitor |
| WO2013012918A1 (en) | 2011-07-19 | 2013-01-24 | Infinity Pharmaceuticals Inc. | Heterocyclic compounds and uses thereof |
| AU2012284088B2 (en) | 2011-07-19 | 2015-10-08 | Infinity Pharmaceuticals Inc. | Heterocyclic compounds and uses thereof |
| CA2846431A1 (en) | 2011-08-29 | 2013-03-07 | Infinity Pharmaceuticals Inc. | Heterocyclic compounds and uses thereof |
| LT2870157T (lt) | 2012-07-04 | 2017-12-11 | Rhizen Pharmaceuticals S.A. | Selektyvieji pi3k delta inhibitoriai |
| KR20150032340A (ko) * | 2012-07-24 | 2015-03-25 | 파마시클릭스, 인코포레이티드 | 브루톤 티로신 키나제(btk)의 억제제에 대한 내성과 관련된 돌연변이 |
| CN105102000B (zh) | 2012-11-01 | 2021-10-22 | 无限药品公司 | 使用pi3激酶亚型调节剂的癌症疗法 |
| WO2015160975A2 (en) * | 2014-04-16 | 2015-10-22 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| EP3474856B1 (en) * | 2016-06-24 | 2022-09-14 | Infinity Pharmaceuticals, Inc. | Combination therapies |
-
2014
- 2014-05-30 SG SG10201709926VA patent/SG10201709926VA/en unknown
- 2014-05-30 CA CA2914284A patent/CA2914284A1/en not_active Abandoned
- 2014-05-30 KR KR1020157036896A patent/KR20160013204A/ko not_active Ceased
- 2014-05-30 WO PCT/US2014/040337 patent/WO2014194254A1/en not_active Ceased
- 2014-05-30 US US14/292,475 patent/US20140377258A1/en not_active Abandoned
- 2014-05-30 US US14/894,854 patent/US20160113932A1/en not_active Abandoned
- 2014-05-30 CN CN201480043018.8A patent/CN105682658B/zh active Active
- 2014-05-30 JP JP2016517058A patent/JP6556702B2/ja active Active
- 2014-05-30 EP EP20194640.7A patent/EP3811974A1/en not_active Withdrawn
- 2014-05-30 ES ES14804451T patent/ES2834638T3/es active Active
- 2014-05-30 MX MX2015016277A patent/MX373584B/es active IP Right Grant
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- 2014-05-30 BR BR112015029969A patent/BR112015029969A2/pt not_active Application Discontinuation
- 2014-05-30 RU RU2015156069A patent/RU2705204C2/ru active
- 2014-05-30 RU RU2019134551A patent/RU2019134551A/ru unknown
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- 2014-05-30 AU AU2014273946A patent/AU2014273946B2/en active Active
- 2014-05-30 EP EP14804451.4A patent/EP3003309B1/en active Active
-
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- 2015-11-26 ZA ZA2015/08711A patent/ZA201508711B/en unknown
- 2015-11-29 IL IL24282615A patent/IL242826B/en active IP Right Grant
-
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- 2017-01-31 US US15/421,020 patent/US20170360795A1/en not_active Abandoned
-
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- 2019-07-10 JP JP2019128045A patent/JP6870185B2/ja active Active
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-
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- 2022-12-12 US US18/064,880 patent/US20230364097A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120183535A1 (en) * | 2010-06-03 | 2012-07-19 | Pharmacyclics, Inc. | use of inhibitors of bruton's tyrosine kinase (btk) |
| WO2013059738A2 (en) * | 2011-10-19 | 2013-04-25 | Pharmacyclics, Inc. | Use of inhibitors of bruton's tyrosine kinase (btk) |
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