JP2008514726A5 - - Google Patents
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- JP2008514726A5 JP2008514726A5 JP2007534826A JP2007534826A JP2008514726A5 JP 2008514726 A5 JP2008514726 A5 JP 2008514726A5 JP 2007534826 A JP2007534826 A JP 2007534826A JP 2007534826 A JP2007534826 A JP 2007534826A JP 2008514726 A5 JP2008514726 A5 JP 2008514726A5
- Authority
- JP
- Japan
- Prior art keywords
- combination
- aryl
- cancer
- cancer cells
- amine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 4
- 125000003118 aryl group Chemical group 0.000 claims 3
- 230000002401 inhibitory effect Effects 0.000 claims 3
- 240000001340 Gmelina philippensis Species 0.000 claims 2
- 108009000301 Hedgehog Signaling Pathway Proteins 0.000 claims 2
- 150000008065 acid anhydrides Chemical class 0.000 claims 2
- 150000001299 aldehydes Chemical class 0.000 claims 2
- 125000003342 alkenyl group Chemical group 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 2
- 125000000304 alkynyl group Chemical group 0.000 claims 2
- 150000001408 amides Chemical class 0.000 claims 2
- 150000001412 amines Chemical class 0.000 claims 2
- 239000002246 antineoplastic agent Substances 0.000 claims 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 2
- 150000003857 carboxamides Chemical class 0.000 claims 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 2
- 150000002148 esters Chemical class 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 150000002466 imines Chemical class 0.000 claims 2
- 239000003112 inhibitor Substances 0.000 claims 2
- 150000002576 ketones Chemical class 0.000 claims 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 2
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims 2
- LFGREXWGYUGZLY-UHFFFAOYSA-N oxophosphanyl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 claims 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims 2
- NJRWNWYFPOFDFN-UHFFFAOYSA-L phosphonate(2-) Chemical compound [O-][P]([O-])=O NJRWNWYFPOFDFN-UHFFFAOYSA-L 0.000 claims 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims 2
- 230000035755 proliferation Effects 0.000 claims 2
- 150000003346 selenoethers Chemical class 0.000 claims 2
- -1 silyloxy, amino Chemical group 0.000 claims 2
- 230000008410 smoothened signaling pathway Effects 0.000 claims 2
- 150000003568 thioethers Chemical class 0.000 claims 2
- 150000003573 thiols Chemical class 0.000 claims 2
- REJLGAUYTKNVJM-AZBBVAELSA-N α-Tomatine Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4C[C@H]5[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@@H]([C@@]1(NC[C@@H](C)CC1)O5)C)[C@@H]1OC[C@@H](O)[C@H](O)[C@H]1O REJLGAUYTKNVJM-AZBBVAELSA-N 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 1
- QASFUMOKHFSJGL-LAFRSMQTSA-N Cyclopamine Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H](CC2=C3C)[C@@H]1[C@@H]2CC[C@@]13O[C@@H]2C[C@H](C)CN[C@H]2[C@H]1C QASFUMOKHFSJGL-LAFRSMQTSA-N 0.000 claims 1
- RCINICONZNJXQF-MZXODVADSA-N Intaxel Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 229960001592 Paclitaxel Drugs 0.000 claims 1
- 208000008443 Pancreatic Carcinoma Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 230000001946 anti-microtubular Effects 0.000 claims 1
- 201000011231 colorectal cancer Diseases 0.000 claims 1
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004435 hydrogen atoms Chemical class [H]* 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 150000003335 secondary amines Chemical class 0.000 claims 1
- 229930003352 steroid alkaloids Natural products 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 229930003347 taxol Natural products 0.000 claims 1
- 230000001225 therapeutic Effects 0.000 claims 1
Claims (7)
- ヘッジホッグシグナル経路を発現する癌細胞の成長又は増殖を低下又は阻害するのに使用される治療の組み合わせであって、ヘッジホッグ阻害剤及び抗微小管化学療法薬の有効量を含むことを特徴とする組み合わせ。
- 前記ヘッジホッグ阻害剤が、下式(I)のステロイドアルカロイドである請求項１記載の組み合わせ。
R2、R3、R4、及びR5は、各々が結合している環の１以上の置換基を表し、各々に対して、独立して、水素、ハロゲン、アルキル、アルケニル、アルキニル、アリール、ヒドロキシル、=O、=S、アルコキシル、シリルオキシ、アミノ、ニトロ、チオール、アミン、イミン、アミド、ホスホリル、ホスホネート、ホスフィン、カルボニル、カルボキシル、カルボキサミド、酸無水物、シリル、エーテル、チオエーテル、アルキルスルホニル、アリールスルホニル、セレノエーテル、ケトン、アルデヒド、エステル、又は(CH2)m-R8を表し、
R6、R7、及びR'7は、存在しないか又は独立して、ハロゲン、アルキル、アルケニル、アルキニル、アリール、ヒドロキシル、=O、=S、アルコキシル、シリルオキシ、アミノ、ニトロ、チオール、アミン、イミン、アミド、ホスホリル、ホスホネート、ホスフィン、カルボニル、カルボキシル、カルボキサミド、酸無水物、シリル、エーテル、チオエーテル、アルキルスルホニル、アリールスルホニル、セレノエーテル、ケトン、アルデヒド、エステル、又は(CH2)m-R8を表すか、又は
R6及びR7、又はR7及びR'7は、R6、R7、又はR'7の１以上が存在してそれらに第一又は第二アミンが含まれるという条件で、置換又は未置換の単環又は多環を一緒に形成し、
R8は、アリール、シクロアルキル、シクロアルケニル、複素環、又は多環を表し、かつmは０乃至８の整数である。) - 前記ステロイドアルカロイドが、シクロパミン又はジェルビンである請求項２記載の組み合わせ。
- 前記化学療法薬が、タキソールである請求項１記載の組み合わせ。
- 有効線量の放射線の併用を更に含む請求項１記載の組み合わせ。
- 前記細胞が、前立腺癌、肺癌、乳癌、結腸直腸癌、又は膵臓癌の細胞である請求項１記載の組み合わせ。
- ヘッジホッグシグナル経路を発現する癌細胞の成長又は増殖を低下又は阻害するのに使用するための、有効量の放射線と組み合わせて使用されるステロイドアルカロイドを含むことを特徴とする治療組成物。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US61461704P | 2004-09-30 | 2004-09-30 | |
| US67520705P | 2005-04-27 | 2005-04-27 | |
| PCT/US2005/035331 WO2006039569A1 (en) | 2004-09-30 | 2005-09-30 | Combination therapy of hedgehog inhibitors, radiation and chemotherapeutic agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008514726A JP2008514726A (ja) | 2008-05-08 |
| JP2008514726A5 true JP2008514726A5 (ja) | 2008-11-20 |
Family
ID=35717528
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007534826A Pending JP2008514726A (ja) | 2004-09-30 | 2005-09-30 | ヘッジホッグ阻害剤、放射線及び化学療法薬の併用療法 |
Country Status (3)
| Country | Link |
|---|---|
| US (2) | US20070281040A1 (ja) |
| JP (1) | JP2008514726A (ja) |
| WO (1) | WO2006039569A1 (ja) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2005280112B2 (en) * | 2004-08-27 | 2012-07-19 | Infinity Pharmaceuticals, Inc. | Cyclopamine analogues and methods of use thereof |
| WO2007123511A2 (en) * | 2006-03-24 | 2007-11-01 | Infinity Pharmaceuticals, Inc. | Dosing regimens for the treatment of cancer |
| TWI433674B (zh) | 2006-12-28 | 2014-04-11 | Infinity Discovery Inc | 環杷明（ｃｙｃｌｏｐａｍｉｎｅ）類似物類 |
| EP2129677B1 (en) * | 2007-03-07 | 2014-12-17 | Infinity Discovery, Inc. | Heterocyclic cyclopamine analogs and methods of use thereof |
| JP2010520310A (ja) * | 2007-03-07 | 2010-06-10 | インフィニティ・ディスカバリー・インコーポレイテッド | シクロパミンラクタム類似体及びその使用方法 |
| US20100297118A1 (en) * | 2007-12-27 | 2010-11-25 | Macdougall John | Therapeutic Cancer Treatments |
| BRPI0821779A2 (pt) * | 2007-12-27 | 2019-09-24 | Infinity Pharmaceuticals Inc | tratamento terapêutico de câncer |
| ES2717797T3 (es) | 2007-12-27 | 2019-06-25 | Infinity Pharmaceuticals Inc | Métodos para reducción estereoselectiva de derivados de 4-en-3-ona de ciclopamina |
| CN102574791A (zh) | 2009-08-05 | 2012-07-11 | 无限药品股份有限公司 | 环杷明类似物的酶促转氨基反应 |
| PL2470173T3 (pl) * | 2009-08-25 | 2016-11-30 | Leczenie skojarzone nanocząstkowymi kompozycjami taksanu i inhibitorów hedgehog | |
| EP2501237A1 (en) * | 2009-11-06 | 2012-09-26 | Infinity Pharmaceuticals, Inc. | Oral formulations of a hedgehog pathway inhibitor |
| WO2011088404A1 (en) * | 2010-01-15 | 2011-07-21 | Infinity Pharmaceuticals , Inc | Treatment of fibrotic conditions using hedgehog inhibitors |
| US20120010229A1 (en) * | 2010-07-08 | 2012-01-12 | Macdougall John R | Therapeutic regimens for hedgehog-associated cancers |
| US9376447B2 (en) | 2010-09-14 | 2016-06-28 | Infinity Pharmaceuticals, Inc. | Transfer hydrogenation of cyclopamine analogs |
| US8945627B2 (en) | 2011-05-05 | 2015-02-03 | Wisconsin Alumni Research Foundation | Micelles for the solubilization of gossypol |
| EP2715366B1 (en) * | 2011-06-02 | 2017-07-19 | Novartis AG | Biomarkers for hedgehog inhibitor therapy |
| WO2016196928A1 (en) | 2015-06-04 | 2016-12-08 | PellePharm, Inc. | Topical formulations for delivery of hedgehog inhibitor compounds and use thereof |
| CN105017519A (zh) * | 2015-07-20 | 2015-11-04 | 湖南华腾制药有限公司 | 一种聚乙二醇修饰的小分子药物的制备方法 |
| US10507208B2 (en) | 2015-10-12 | 2019-12-17 | Vikash J. BHAGWANDIN | Compositions, packaged pharmaceuticals, and methods of using hedgehog pathway modulators for the sensitization of resistant tumors |
| WO2018191541A1 (en) * | 2017-04-12 | 2018-10-18 | Bhagwandin Vikash J | Compositions, packaged pharmaceuticals, and methods of using posaconazole for the sensitization of resistant tumors |
| US11173325B2 (en) | 2017-07-21 | 2021-11-16 | Varian Medical Systems, Inc. | Methods of use of ultra-high dose rate radiation and therapeutic agent |
| US20200368246A1 (en) * | 2017-11-17 | 2020-11-26 | Jaeyoung Yoon | Combination therapy targeting cancer associated with the hedgehog pathway |
| EP3823618A1 (en) * | 2018-07-19 | 2021-05-26 | Varian Medical Systems, Inc. | Methods of use of ultra-high dose rate radiation and therapeutic agents |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5359115A (en) * | 1992-03-26 | 1994-10-25 | Affymax Technologies, N.V. | Methods for the synthesis of phosphonate esters |
| US5288514A (en) * | 1992-09-14 | 1994-02-22 | The Regents Of The University Of California | Solid phase and combinatorial synthesis of benzodiazepine compounds on a solid support |
| US5362899A (en) * | 1993-09-09 | 1994-11-08 | Affymax Technologies, N.V. | Chiral synthesis of alpha-aminophosponic acids |
| US5712171A (en) * | 1995-01-20 | 1998-01-27 | Arqule, Inc. | Method of generating a plurality of chemical compounds in a spatially arranged array |
| SE9600229D0 (sv) * | 1996-01-23 | 1996-01-23 | Pharmacia Ab | Novel potentiating agents |
| PT910382E (pt) * | 1996-04-26 | 2003-10-31 | Genaera Corp | Esqualamina em combinacao com outros agentes anti-cancro para o tratamento de tumores |
| US6639051B2 (en) * | 1997-10-20 | 2003-10-28 | Curis, Inc. | Regulation of epithelial tissue by hedgehog-like polypeptides, and formulations and uses related thereto |
| US6432970B2 (en) * | 1998-04-09 | 2002-08-13 | Johns Hopkins University School Of Medicine | Inhibitors of hedgehog signaling pathways, compositions and uses related thereto |
| US6291516B1 (en) * | 1999-01-13 | 2001-09-18 | Curis, Inc. | Regulators of the hedgehog pathway, compositions and uses related thereto |
| US20050080138A1 (en) * | 1999-09-16 | 2005-04-14 | Curis, Inc. | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
| JP4994552B2 (ja) * | 1999-09-16 | 2012-08-08 | キュリス，インコーポレイテッド | ヘッジホッグシグナル伝達経路のメディエーター、組成物及びそれらと関連する利用 |
| AU781524B2 (en) * | 1999-10-13 | 2005-05-26 | Johns Hopkins University School Of Medicine, The | Regulators of the hedgehog pathway, compositions and uses related thereto |
| US6552016B1 (en) * | 1999-10-14 | 2003-04-22 | Curis, Inc. | Mediators of hedgehog signaling pathways, compositions and uses related thereto |
| WO2001041786A1 (en) * | 1999-12-10 | 2001-06-14 | The General Hospital Corporation | METHODS TO STIMULATE INSULIN PRODUCTION BY PANCREATIC β-CELLS |
| IL133809A0 (en) * | 1999-12-30 | 2001-04-30 | Yeda Res & Dev | Steroidal alkaloids and pharmaceutical compositions comprising them |
| US6613798B1 (en) * | 2000-03-30 | 2003-09-02 | Curis, Inc. | Small organic molecule regulators of cell proliferation |
| US6683192B2 (en) * | 2000-03-30 | 2004-01-27 | Curis, Inc. | Small organic molecule regulators of cell proliferation |
| US6683108B1 (en) * | 2000-03-30 | 2004-01-27 | Curis, Inc. | Agonists of hedgehog signaling pathways and uses related thereto |
| EP1411938B1 (en) * | 2001-07-02 | 2005-07-06 | Tas, Sinan | Use of cyclopamine for the manufacture of a medicament for the treatemnt of psoriasis |
-
2005
- 2005-09-30 US US11/576,310 patent/US20070281040A1/en not_active Abandoned
- 2005-09-30 JP JP2007534826A patent/JP2008514726A/ja active Pending
- 2005-09-30 WO PCT/US2005/035331 patent/WO2006039569A1/en active Application Filing
-
2010
- 2010-10-27 US US12/913,459 patent/US20110046211A1/en not_active Abandoned
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