AU2001277854B2 - Modulators of cellular proliferation and angiogenesis, methods for use and identification thereof - Google Patents
Modulators of cellular proliferation and angiogenesis, methods for use and identification thereof Download PDFInfo
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- AU2001277854B2 AU2001277854B2 AU2001277854A AU2001277854A AU2001277854B2 AU 2001277854 B2 AU2001277854 B2 AU 2001277854B2 AU 2001277854 A AU2001277854 A AU 2001277854A AU 2001277854 A AU2001277854 A AU 2001277854A AU 2001277854 B2 AU2001277854 B2 AU 2001277854B2
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- hgf
- pyrazol
- thienyl
- pyrazole
- chlorophenyl
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| US60662800A | 2000-06-29 | 2000-06-29 | |
| US09/606,628 | 2000-06-29 | ||
| US27617001P | 2001-03-15 | 2001-03-15 | |
| US60/276,170 | 2001-03-15 | ||
| PCT/US2001/020849 WO2002002593A2 (en) | 2000-06-29 | 2001-06-29 | Modulators of cellular proliferation and angiogenesis, methods for use and identification thereof |
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| AU2001277854A1 AU2001277854A1 (en) | 2002-04-11 |
| AU2001277854B2 true AU2001277854B2 (en) | 2007-03-01 |
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| US7192976B2 (en) | 2002-12-21 | 2007-03-20 | Angion Biomedica Corporation | Small molecule modulators of hepatocyte growth factor (scatter factor) activity |
| KR101254371B1 (ko) | 2003-07-18 | 2013-05-02 | 암젠 프레몬트 인코포레이티드 | 간세포 성장인자에 결합하는 분리된 항체 |
| CN100363383C (zh) * | 2003-07-21 | 2008-01-23 | 中国人民解放军军事医学科学院基础医学研究所 | 能够与金葡菌毒力因子调控蛋白结合的小分子多肽及其医药用途 |
| JP2008500015A (ja) * | 2003-10-29 | 2008-01-10 | ラモト アット テル アヴィヴ ユニヴァーシティ リミテッド | 血管形成ペプチドおよびその使用 |
| US20060008844A1 (en) * | 2004-06-17 | 2006-01-12 | Avidia Research Institute | c-Met kinase binding proteins |
| AU2005327921A1 (en) * | 2004-11-01 | 2006-08-31 | University Of Southern California | Novel compounds for treatment of cancer and disorders associated with angiogenesis function |
| US7947682B2 (en) * | 2004-12-29 | 2011-05-24 | University Of Southern California | Substituted N′-pyrrolo[1,2-a]quinoxalin-4-yl-hydrazides as anti-cancer agents |
| US7871978B2 (en) | 2004-11-04 | 2011-01-18 | University Of Virginia Patent Foundation | Bone tropic peptides |
| JP4171061B2 (ja) | 2005-02-09 | 2008-10-22 | アーキュール,インコーポレーテッド | マレイミド誘導体、医薬組成物、および癌の治療のためのその使用 |
| US7879898B1 (en) | 2006-02-14 | 2011-02-01 | Angion Biomedica Corp. | Hepatocyte growth factor pathway activators in chronic obstructive pulmonary disease |
| US8236761B2 (en) | 2006-07-07 | 2012-08-07 | Washington State University Research Foundation | C-Met receptor regulation by angiotensin IV (AT4) receptor ligands |
| EP2043675A2 (en) * | 2006-07-07 | 2009-04-08 | Washington State University Research Foundation | C-met receptor regulation by angiotensin iv (at4) receptor ligands |
| WO2008047370A2 (en) | 2006-10-19 | 2008-04-24 | Ramot At Tel Aviv University Ltd. | Compositions and methods for inducing angiogenesis |
| EP2173748B1 (en) | 2007-06-22 | 2011-08-31 | ArQule, Inc. | Indolyl pyrrolidines for the treatment of cancer |
| JP5425060B2 (ja) | 2007-06-22 | 2014-02-26 | アークル インコーポレイテッド | ピロリジノン、ピロリジン−2,5−ジオン、ピロリジンおよびチオスクシンイミド誘導体、癌の治療のための組成物および方法 |
| JP2010530885A (ja) | 2007-06-22 | 2010-09-16 | アークル インコーポレイテッド | キナゾリノン化合物およびその使用方法 |
| US8247374B2 (en) | 2007-11-09 | 2012-08-21 | New York Medical College | Methods and compositions for the repair and/or regeneration of damaged myocardium using cytokines and variants thereof |
| CN102149379A (zh) | 2008-07-10 | 2011-08-10 | 安吉翁生物医药有限公司 | 调节肝细胞生长因子(分散因子)活性的方法和肝细胞生长因子(分散因子)活性的小分子调节剂组合物 |
| CN103003307B (zh) | 2010-03-10 | 2017-08-11 | 根马布股份公司 | 抗c‑MEt的单克隆抗体 |
| US20130190376A1 (en) * | 2010-10-05 | 2013-07-25 | David E. Smith | Methods of use of small molecule modulators of hepatocyte growth factor (scatter factor) activity |
| JP2012193155A (ja) * | 2011-03-18 | 2012-10-11 | Tohoku Univ | 金属酸化物ナノ粒子の結晶面を認識することが出来るペプチド |
| WO2013113722A1 (en) | 2012-01-30 | 2013-08-08 | Universiteit Gent | Anti-invasive compounds |
| WO2016123163A2 (en) | 2015-01-27 | 2016-08-04 | Kardiatonos, Inc. | Biomarkers of vascular disease |
| EP4420723A3 (en) | 2018-10-12 | 2024-12-04 | Theradaptive, Inc. | Polypeptides including a beta-tricalcium phosphate-binding sequence and uses thereof |
| CA3133803A1 (en) | 2019-04-11 | 2020-10-15 | Angion Biomedica Corp. | Solid forms of (e)-3-[2-(2-thienyl)vinyl]-1h-pyrazole |
| AU2021254751B2 (en) | 2020-04-15 | 2025-01-30 | Theradaptive, Inc. | Compositions and methods for targeted therapeutic delivery to bone |
| CN115317469A (zh) * | 2021-05-11 | 2022-11-11 | 四川大学 | 白及联菲c在制备预防和/或治疗乳腺癌或乳腺癌转移的药物中的用途 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0662130B1 (en) * | 1992-09-18 | 1997-11-26 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES | A method of producing hepatocyte growth factor and a cell line |
| US5646036A (en) * | 1995-06-02 | 1997-07-08 | Genentech, Inc. | Nucleic acids encoding hepatocyte growth factor receptor antagonist antibodies |
| DE69739856D1 (de) * | 1996-07-03 | 2010-06-02 | Genentech Inc | Agonisten für den rezeptor des hepatozyten-wachstumsfaktors und deren anwendungen |
| HUP0102612A2 (hu) * | 1998-03-12 | 2001-11-28 | Novo Nordisk A/S | Fehérje-tirozinfoszfatázokat moduláló vegyületek és ezeket tartalmazó gyógyászati készítmények |
| AU5382200A (en) * | 1999-06-15 | 2001-01-02 | University Health Network | Muc1 ligands |
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- 2001-06-29 WO PCT/US2001/020849 patent/WO2002002593A2/en not_active Ceased
- 2001-06-29 AU AU7785401A patent/AU7785401A/xx active Pending
- 2001-06-29 AU AU2001277854A patent/AU2001277854B2/en not_active Ceased
- 2001-06-29 CA CA2452445A patent/CA2452445C/en not_active Expired - Fee Related
- 2001-06-29 JP JP2002507845A patent/JP4993834B2/ja not_active Expired - Fee Related
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|---|---|
| EP1355921A2 (en) | 2003-10-29 |
| WO2002002593A2 (en) | 2002-01-10 |
| JP4993834B2 (ja) | 2012-08-08 |
| CA2452445C (en) | 2011-02-15 |
| AU7785401A (en) | 2002-01-14 |
| JP2005520480A (ja) | 2005-07-14 |
| CA2452445A1 (en) | 2002-01-10 |
| WO2002002593A3 (en) | 2003-08-07 |
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