CA2761896A1 - Cyclin dependent kinase inhibitors and methods of use - Google Patents
Cyclin dependent kinase inhibitors and methods of use Download PDFInfo
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- CA2761896A1 CA2761896A1 CA2761896A CA2761896A CA2761896A1 CA 2761896 A1 CA2761896 A1 CA 2761896A1 CA 2761896 A CA2761896 A CA 2761896A CA 2761896 A CA2761896 A CA 2761896A CA 2761896 A1 CA2761896 A1 CA 2761896A1
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- cdk4
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| US8691830B2 (en) | 2010-10-25 | 2014-04-08 | G1 Therapeutics, Inc. | CDK inhibitors |
| CN103429243B (zh) | 2010-10-25 | 2016-06-08 | G1治疗公司 | Cdk抑制剂 |
| JP2013545758A (ja) | 2010-11-17 | 2013-12-26 | ザ ユニバーシティ オブ ノース カロライナ アット チャペル ヒル | 増殖性キナーゼｃｄｋ４及びｃｄｋ６の阻害による虚血からの腎組織の保護 |
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| CA2904054A1 (en) | 2013-03-15 | 2014-09-25 | Concert Pharmaceuticals, Inc. | Deuterated palbociclib |
| JP6435315B2 (ja) | 2013-03-15 | 2018-12-05 | ジー１、セラピューティクス、インコーポレイテッドＧ１ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． | 高活性抗新生物薬及び抗増殖剤 |
| US20140274896A1 (en) * | 2013-03-15 | 2014-09-18 | G1 Therapeutics, Inc. | Transient Protection of Hematopoietic Stem and Progenitor Cells Against Ionizing Radiation |
| SI3033086T1 (sl) | 2013-08-14 | 2022-01-31 | Novartis Ag | Kombinirana terapija za zdravljenje raka |
| ES2674361T3 (es) * | 2013-08-28 | 2018-06-29 | Novartis Ag | Combinación de un inhibidor de ALK y un inhibidor de CDK para el tratamiento de enfermedades celulares proliferativas |
| CA2927541C (en) | 2013-10-15 | 2021-06-08 | Radux Devices, LLC | Securing a medical device to a valve instrument |
| WO2015069736A1 (en) | 2013-11-08 | 2015-05-14 | The Mclean Hospital Corporation | METHODS FOR EFFICIENT GENERATION OF GABAergic INTERNEURONS FROM PLURIPOTENT STEM CELLS |
| US20150297608A1 (en) | 2014-04-17 | 2015-10-22 | G1 Therapeutics, Inc. | Tricyclic Lactams for Use as Anti-Neoplastic and Anti-Proliferative Agents |
| CA2954189A1 (en) * | 2014-07-26 | 2016-02-04 | Sunshine Lake Pharma Co., Ltd. | 2-amino-pyrido[2,3-d]pyrimidin-7(8h)-one derivatives as cdk inhibitors and uses thereof |
| WO2016040184A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(3h-imidazo[4,5-b]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
| WO2016040190A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(3h-imidazo[4,5-b]pyridin-2-yl)-1h-pyrazolo[3,4-b]pyridine and therapeutic uses thereof |
| WO2016040185A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 2-(1h-indazol-3-yl)-3h-imidazo[4,5-b]pyridine and therapeutic uses thereof |
| WO2016040181A1 (en) | 2014-09-08 | 2016-03-17 | Samumed, Llc | 3-(1h-imidazo[4,5-c]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridine and therapeutic uses thereof |
| WO2016040848A1 (en) | 2014-09-12 | 2016-03-17 | G1 Therapeutics, Inc. | Treatment of rb-negative tumors using topoisomerase inhibitors in combination with cyclin dependent kinase 4/6 inhibitors |
| WO2016040858A1 (en) | 2014-09-12 | 2016-03-17 | G1 Therapeutics, Inc. | Combinations and dosing regimes to treat rb-positive tumors |
| CN104610254B (zh) * | 2015-01-26 | 2017-02-01 | 新发药业有限公司 | 一种帕博赛布的低成本制备方法 |
| US10519169B2 (en) | 2015-08-03 | 2019-12-31 | Samumed, Llc | 3-(1H-pyrrolo[2,3-C]pyridin-2-yl)-1 H-pyrazolo[4,3-B]pyridines and therapeutic uses thereof |
| WO2017023980A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(1h-pyrrolo[2,3-b]pyridin-2-yl)-1h-pyrazolo[3,4-c]pyridines and therapeutic uses thereof |
| US10604512B2 (en) | 2015-08-03 | 2020-03-31 | Samumed, Llc | 3-(1H-indol-2-yl)-1H-indazoles and therapeutic uses thereof |
| US10285983B2 (en) | 2015-08-03 | 2019-05-14 | Samumed, Llc | 3-(1H-pyrrolo[2,3-B]pyridin-2-yl)-1H-pyrazolo[3,4-B] pyridines and therapeutic uses thereof |
| US10350199B2 (en) | 2015-08-03 | 2019-07-16 | Samumed, Llc | 3-(1h-pyrrolo[2,3-b]pyridin-2-yl)-1h-indazoles and therapeutic uses thereof |
| WO2017024015A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(3h-imidazo[4,5-b]pyridin-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
| US10463651B2 (en) | 2015-08-03 | 2019-11-05 | Samumed, Llc | 3-(1H-pyrrolo[3,2-C]pyridin-2-YL)-1H-indazoles and therapeutic uses thereof |
| WO2017023989A1 (en) | 2015-08-03 | 2017-02-09 | Samumed, Llc. | 3-(1h-benzo[d]imidazol-2-yl)-1h-pyrazolo[4,3-b]pyridines and therapeutic uses thereof |
| US10383861B2 (en) | 2015-08-03 | 2019-08-20 | Sammumed, LLC | 3-(1H-pyrrolo[2,3-C]pyridin-2-yl)-1H-pyrazolo[3,4-C]pyridines and therapeutic uses thereof |
| CN106565611A (zh) * | 2015-10-13 | 2017-04-19 | 华东师范大学 | 一种1-（4-环戊胺基-2-甲硫基嘧啶-5-）基乙酮的制备方法 |
| CN108473491A (zh) | 2015-11-06 | 2018-08-31 | 萨穆梅德有限公司 | 2-(1h-吲唑-3-基)-3h-咪唑并[4,5-c]吡啶以及其抗炎用途 |
| WO2017172734A1 (en) * | 2016-03-29 | 2017-10-05 | Mayo Foundation For Medical Education And Research | Treating cancer metastasis |
| DK3464285T3 (da) | 2016-06-01 | 2022-12-19 | Biosplice Therapeutics Inc | Fremgangsmåde til fremstilling af n-(5-(3-(7-(3-fluorphenyl)-3h-imidazo[4,5-c]pyridin-2-yl)-1h-indazol-5-yl)pyridin-3-yl)-3-methylbutanamid |
| EP3528808B1 (en) | 2016-10-21 | 2021-10-06 | BioSplice Therapeutics, Inc. | Methods of using indazole-3-carboxamides and their use as wnt/b-catenin signaling pathway inhibitors |
| MA46696A (fr) | 2016-11-07 | 2019-09-11 | Samumed Llc | Formulations injectables à dose unique prêtes à l'emploi |
| AU2017372856B9 (en) | 2016-12-05 | 2024-01-04 | Pharmacosmos Holding A/S | Preservation of immune response during chemotherapy regimens |
| AR110728A1 (es) | 2017-01-06 | 2019-04-24 | G1 Therapeutics Inc | Terapia combinada para el tratamiento del cáncer |
| US11395821B2 (en) | 2017-01-30 | 2022-07-26 | G1 Therapeutics, Inc. | Treatment of EGFR-driven cancer with fewer side effects |
| WO2018202866A1 (en) * | 2017-05-05 | 2018-11-08 | Fundación Para La Investigación Hospital Clínico Universitario De Valencia Incliva | Medical uses of p15/p16 agonists |
| CA3067873A1 (en) | 2017-06-29 | 2019-01-03 | G1 Therapeutics, Inc. | Morphic forms of g1t38 and methods of manufacture thereof |
| SG11202005937QA (en) | 2018-01-08 | 2020-07-29 | G1 Therapeutics Inc | G1t38 superior dosage regimes |
| HUE064843T2 (hu) | 2018-05-14 | 2024-04-28 | Pfizer | Orális oldat kiszerelés |
| RS67557B1 (sr) | 2018-08-24 | 2026-01-30 | Pharmacosmos Holding As | Unapređena sinteza 1,4-diazaspiro[5.5]undekan-3-ona |
| ES3004338T3 (en) | 2018-09-10 | 2025-03-12 | Mirati Therapeutics Inc | Combination therapies |
| US20210340502A1 (en) * | 2018-09-28 | 2021-11-04 | The Mclean Hospital Corporation | Generation of Post-Mitotic Migratory Cortical Interneurons |
| EP3797776B1 (en) | 2019-09-30 | 2025-07-23 | Universitätsmedizin Mainz | Cdk4/6 inhibitors for the treatment of psoriasis |
| US10988479B1 (en) | 2020-06-15 | 2021-04-27 | G1 Therapeutics, Inc. | Morphic forms of trilaciclib and methods of manufacture thereof |
| WO2022113003A1 (en) | 2020-11-27 | 2022-06-02 | Rhizen Pharmaceuticals Ag | Cdk inhibitors |
| WO2022149057A1 (en) | 2021-01-05 | 2022-07-14 | Rhizen Pharmaceuticals Ag | Cdk inhibitors |
| WO2023207875A1 (en) * | 2022-04-25 | 2023-11-02 | Onquality Pharmaceuticals China Ltd. | Cdk inhibitors, pharmaceutical compositions, and therapeutic applications |
| CN115364195B (zh) * | 2022-09-28 | 2026-03-17 | 中南大学湘雅二医院 | Thiostrepton在制备预防和治疗硬皮病的药物中的应用 |
| WO2025085360A1 (en) | 2023-10-16 | 2025-04-24 | The Board Of Regents Of The University Of Oklahoma | Heteroarotinoids and/or cdk4/6 inhibitors for treating human papillomavirus (hpv)-induced dysplasias, warts, and cancer in hpv-infected subjects |
Family Cites Families (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5739110A (en) * | 1994-09-12 | 1998-04-14 | Biomeasure Inc. | Protection of hemopoietic cells |
| US5591855A (en) | 1994-10-14 | 1997-01-07 | Cephalon, Inc. | Fused pyrrolocarbazoles |
| US5628984A (en) | 1995-07-31 | 1997-05-13 | University Of North Carolina At Chapel Hill | Method of detecting lung disease |
| KR20000070751A (ko) | 1997-02-05 | 2000-11-25 | 로즈 암스트롱, 크리스틴 에이. 트러트웨인 | 세포 증식 억제제로서의 피리도[2,3-ｄ]피리미딘 및 4-아미노피리미딘 |
| JP4562815B2 (ja) * | 1997-05-21 | 2010-10-13 | ジェネンテック， インコーポレイテッド | トロンボポエチンの新規な投与 |
| GB9718913D0 (en) | 1997-09-05 | 1997-11-12 | Glaxo Group Ltd | Substituted oxindole derivatives |
| US6262096B1 (en) | 1997-11-12 | 2001-07-17 | Bristol-Myers Squibb Company | Aminothiazole inhibitors of cyclin dependent kinases |
| US20040006074A1 (en) | 1998-04-28 | 2004-01-08 | The Government Of The United States Of America | Cyclin dependent kinase (CDK)4 inhibitors and their use for treating cancer |
| AU778735B2 (en) | 1998-06-16 | 2004-12-16 | Centre National De La Recherche Scientifique | Fused azepinone cyclin dependent kinase inhibitors |
| ATE380548T1 (de) | 1999-01-29 | 2007-12-15 | Univ Illinois | Verwendung von p53 inhibitoren zur behandlung von nebenerscheinungen bei der krebstherapie |
| AU6314900A (en) | 1999-07-26 | 2001-02-13 | Banyu Pharmaceutical Co., Ltd. | Biarylurea derivatives |
| US6387900B1 (en) | 1999-08-12 | 2002-05-14 | Pharmacia & Upjohn S.P.A. | 3(5)-ureido-pyrazole derivatives process for their preparation and their use as antitumor agents |
| US6291504B1 (en) * | 1999-10-20 | 2001-09-18 | Dupont Pharmaceuticals Company | Acylsemicarbazides and their uses |
| US6867198B2 (en) | 1999-12-16 | 2005-03-15 | Eli Lilly And Company | Agents and methods for the treatment of proliferative diseases |
| US7053070B2 (en) | 2000-01-25 | 2006-05-30 | Warner-Lambert Company | Pyrido[2,3-d]pyrimidine-2,7-diamine kinase inhibitors |
| DK1325011T3 (da) | 2000-09-29 | 2004-08-16 | Lilly Co Eli | Fremgangsmåder og forbindelser til behandling af proliferative sygdomme |
| US6706718B2 (en) | 2000-12-01 | 2004-03-16 | Bristol-Myers Squibb Company | 3-(2,4-dimethylthiazol-5-yl)indeno[1,2-c]pyrazol-4-one derivatives and their uses |
| JP4302986B2 (ja) | 2001-02-28 | 2009-07-29 | テンプル・ユニバーシティ−オブ・ザ・コモンウェルス・システム・オブ・ハイアー・エデュケイション | 細胞及び組織をα，β不飽和アリールスルホンにより電離放射線から防護する方法 |
| ATE314370T1 (de) | 2002-01-22 | 2006-01-15 | Warner Lambert Co | 2-(pyridin-2-ylamino)-pyrido(2,3-d)pyrimidin-7- one |
| ITMI20021116A1 (it) | 2002-05-23 | 2003-11-24 | Santoni & C Spa | Macchina circolare per maglieria calzetteria o simile con dispositivodi comando delle platine di abbattitura |
| MXPA05007503A (es) | 2003-01-17 | 2005-09-21 | Warner Lambert Co | Heterociclicos 2-aminopiridina sustituidos como inhibidores de proliferacion celular. |
| CN1835951B (zh) | 2003-07-11 | 2010-06-02 | 沃尼尔·朗伯有限责任公司 | 选择性cdk4抑制剂的羟乙基磺酸盐 |
| WO2005094830A1 (en) | 2004-03-30 | 2005-10-13 | Pfizer Products Inc. | Combinations of signal transduction inhibitors |
| EP2298292A3 (en) | 2004-06-18 | 2011-08-10 | Agennix USA Inc. | Kinase inhibitors for treating cancers |
| EP1846408B1 (en) | 2005-01-14 | 2013-03-20 | Janssen Pharmaceutica NV | 5-membered annelated heterocyclic pyrimidines as kinase inhibitors |
| US20080161355A1 (en) * | 2005-01-21 | 2008-07-03 | Astex Therapeutics Limited | Combinations of Pyrazole Kinase Inhibitors and Further Antitumor Agents |
| EP1963273A2 (en) | 2005-12-22 | 2008-09-03 | Wyeth a Corporation of the State of Delaware | Substituted isoquinoline-1,3(2h,4h)-diones, 1-thioxo-1,4-dihydro-2h-isoquinoline-3-ones and 1,4-dihydro-3(2h)-isoquinolones and use thereof as kinase inhibitors |
| US20070270362A1 (en) * | 2006-05-18 | 2007-11-22 | The University Of Washington | Methods and compositions for prevention or treatment of inflammatory-related diseases and disorders |
| JO3235B1 (ar) | 2006-05-26 | 2018-03-08 | Astex Therapeutics Ltd | مركبات بيررولوبيريميدين و استعمالاتها |
| EP2043651A2 (en) | 2006-07-05 | 2009-04-08 | Exelixis, Inc. | Methods of using igf1r and abl kinase modulators |
| US20080249001A1 (en) * | 2006-10-25 | 2008-10-09 | Ajinomoto Co. Inc. | Agents that alleviate side-effects caused by chemotherapy agents |
| AU2007333791A1 (en) | 2006-12-14 | 2008-06-26 | Panacea Pharmaceuticals, Inc. | Methods of neuroprotection by cyclin-dependent kinase inhibition |
| WO2008079933A2 (en) | 2006-12-22 | 2008-07-03 | Novartis Ag | Heteroaryl-heteroaryl compounds as cdk inhibitors for the treatment of cancer, inflammation and viral infections |
| CN101796063B (zh) * | 2007-04-03 | 2017-03-22 | 拉蒂奥法姆有限责任公司 | 使用糖聚乙二醇化g‑csf的治疗方法 |
| US9259399B2 (en) | 2007-11-07 | 2016-02-16 | Cornell University | Targeting CDK4 and CDK6 in cancer therapy |
| MX2010006457A (es) | 2007-12-19 | 2010-07-05 | Amgen Inc | Compuestos fusionados de piridina, pirimidina y triazina como inhibidores de ciclo celular. |
| EA019094B1 (ru) | 2008-08-22 | 2014-01-30 | Новартис Аг | Пирролопиримидины и их применение |
| CA2738909A1 (en) | 2008-10-01 | 2010-05-06 | The University Of North Carolina At Chapel Hill | Hematopoietic protection against ionizing radiation using selective cyclin-dependent kinase 4/6 inhibitors |
| CN102231984A (zh) | 2008-10-01 | 2011-11-02 | 北卡罗来纳大学查珀尔希尔分校 | 使用选择性细胞周期蛋白依赖性激酶4/6抑制剂对抗化疗化合物的造血防护 |
| EP2429566B1 (en) | 2009-05-13 | 2016-01-06 | The University of North Carolina At Chapel Hill | Cyclin dependent kinase inhibitors and methods of use |
| CN103429243B (zh) | 2010-10-25 | 2016-06-08 | G1治疗公司 | Cdk抑制剂 |
| JP2013545758A (ja) | 2010-11-17 | 2013-12-26 | ザ ユニバーシティ オブ ノース カロライナ アット チャペル ヒル | 増殖性キナーゼｃｄｋ４及びｃｄｋ６の阻害による虚血からの腎組織の保護 |
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| EP2429566A2 (en) | 2012-03-21 |
| US20140227222A1 (en) | 2014-08-14 |
| AU2010248886A1 (en) | 2011-12-01 |
| EP2429566A4 (en) | 2013-09-04 |
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