JP2015509965A - 併用療法によるプロカスパーゼ3活性化 - Google Patents
併用療法によるプロカスパーゼ3活性化 Download PDFInfo
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Abstract
Description
(a)化合物PAC−1:
と、
(b)第2の活性薬物と、
(c)薬学的に許容可能な希釈剤、賦形剤又は担体と、
を含む組成物を提供する。第2の活性薬物は、例えば、エトポシド、ボルテゾミブ、スタウロスポリン、ドキソルビシン、タモキシフェン、シスプラチン、カルボプラチン、パクリタキセル、又は他の化学療法薬若しくは本明細書に記載の活性薬物であり得る。担体は水を含み得、活性薬物を有利に送達するための任意選択の成分、例えば、緩衝液、糖、可溶化剤(例えばシクロデキストリン)又はそれらの種々の組み合わせをさらに含み得る。一実施形態において、シクロデキストリンは2−ヒドロキシプロピル−β−シクロデキストリンである。
他の実施形態において、第2の活性薬物はボルテゾミブであり得、ボルテゾミブの濃度は約50nM〜約20μMであり得る。
他の実施形態において、第2の活性薬物はスタウロスポリンであり得、スタウロスポリンの濃度は約25nM〜約200nMであり得る。
他の実施形態において、第2の活性薬物はドキソルビシンであり得、ドキソルビシンの濃度は約50nM〜約5μMであり得る。
他の実施形態において、第2の活性薬物はタモキシフェンであり得、タモキシフェンの濃度は約5μM〜約50μMであり得る。
他の実施形態において、第2の活性薬物はシスプラチンであり得、シスプラチンの濃度は約5μM〜約150μMであり得る。
他の実施形態において、第2の活性薬物はカルボプラチンであり得、カルボプラチンの濃度は約5μM〜約150μMであり得る。
他の実施形態において、第2の活性薬物はパクリタキセルであり得、パクリタキセルの濃度は約0.5nM〜約15nMであり得る。
及び有効量の第2の活性薬物と接触させるステップを含み、アポトーシスはそれにより癌細胞において誘導される、方法を提供する。一部の実施形態において、第2の活性薬物は、エトポシド、ボルテゾミブ、スタウロスポリン、ドキソルビシン、タモキシフェン、シスプラチン、カルボプラチン又はパクリタキセルである。他の実施形態において、第2の活性薬物は、本明細書において後述される活性薬物である。接触は、インビトロにおけるものであってもよいし、インビボにおけるものであってもよい。癌細胞は、PAC−1及び第2の活性薬物と同時に接触させることができる。あるいは、癌細胞を第2の活性薬物と接触させる前に癌細胞をPAC−1と接触させることができ、又は、癌細胞を第2の活性薬物と接触させた後に癌細胞をPAC−1と接触させることができる。
及び有効量の第2の活性薬物を患者に同時又は逐次に投与するステップを含み、癌はそれにより処置される、方法を提供する。一部の実施形態において、第2の活性薬物は、エトポシド、ボルテゾミブ、スタウロスポリン、ドキソルビシン、タモキシフェン、シスプラチン、カルボプラチン又はパクリタキセルである。他の実施形態において、第2の活性薬物は、本明細書において後述される活性薬物である。化合物PAC−1及び第2の活性薬物は同時に投与することができる。あるいは、化合物PAC−1及び第2の活性薬物は逐次に投与することができる。一実施形態において、化合物PAC−1は第2の活性薬物の前に投与される。他の実施形態において、化合物PAC−1は第2の活性薬物の後に投与することができる。癌は、例えば、リンパ腫、骨肉腫、乳癌、卵巣癌、又は本明細書に記載の他の癌型であり得る。
本明細書において、記載された用語は以下の意味を有する。本明細書で使用されている他のすべての用語及びフレーズは、当業者が理解し得るそれらの通常の意味を有する。そのような通常の意味は、専門用語辞典(例えば、Hawley’s Condensed Chemical Dictionary 14th Edition, by R.J.Lewis, John Wiley & Sons,New York,N.Y.,2001)を参照することによって得ることができる。
プロカスパーゼ活性化化合物−1(PAC−1)(2−(4−ベンジルピペラジン−1−イル)−N−[(2−ヒドロキシ−3−プロパ−2−エニル−フェニル)メチリデンアミノ]アセトアミド)は、癌細胞におけるアポトーシスを選択的に誘導する。PAC−1の構造はFigure1に示され、PAC−1の調製方法は、米国特許出願公開第2012/0040995号(Hergenrother et al.)に開示されている。
(b)BIRモチーフ含有タンパク質の修飾剤(例えば、スルビビン、SMAC模倣体)
(c)微小管又は細胞骨格要素の修飾剤/安定剤又は阻害剤(例えば、パクリタキセル及びドセタキセルなどのタキサン)
(d)アルキル化剤(例えば、シクロホスファミド、DTIC)又は細胞障害性抗生物質(例えばドキソルビシン)
(e)DNA挿入剤(例えば、シスプラチン、カルボプラチン又はオキサリプラチンなどのプラチン)
(f)オートファジー調節剤(例えばテモゾロミド)
(g)腫瘍細胞シグナル伝達阻害剤(例えば、野性型又は変異型EGFRs、braf、Ras、AKT、cMET、mTOR、PI3K、BTK、JAK/STATファミリーメンバー、MEKの阻害剤)
(h)シグナル伝達受容体の阻害剤/修飾剤(例えば、タモキシフェン、EGFR、CD20、CD19に対する抗体、及び腫瘍細胞で過剰発現されるか、慣例的に発現される他のもの)
(i)血管新生の阻害剤/調節剤(例えば、VEGF、VEGFR、アンジオジェニン、アンジオスタチン、TIEタンパク質、エンドスタチン)
(j)免疫媒介性機序の調節剤(例えば、ワクチン、細胞治療、チェックポイント阻害剤、炎症誘発性サイトカイン/抗体、アジュバント)
(k)プロテアソーム阻害剤(例えばボルテゾミブ)
エトポシドはトポイソメラーゼII阻害剤である。エトポシドは、DNA及びトポイソメラーゼII酵素と三元複合体を形成し、DNA鎖の再連結を阻害し、それによって、DNA合成におけるエラーをもたらし、癌細胞のアポトーシスを促進する。PAC−1及びエトポシドによるU−937細胞の併用処置は、低マイクロモル濃度であっても有意なインビトロ活性を示した(Figure2)。
ベルケイド(登録商標)(ボルテゾミブ)は、高い親和性及び特異性で26Sプロテアソームの触媒部位に結合する。正常細胞において、プロテアソームは、ユビキチン化タンパク質の分解によってタンパク質の発現及び機能を制御し、また、異常タンパク質又はミスフォールドタンパク質の細胞を除去する。複数の機序が関与しているようであるが、プロテアソーム阻害はアポトーシス促進因子の分解を阻害することができ、アポトーシス促進経路の抑制に依存する腫瘍細胞でのプログラム細胞死を活性化させることができる。相乗的な活性は、PAC−1及びボルテゾミブによるU−937リンパ腫細胞の組み合わせ処置に関して確認された(Figure3)。
スタウロスポリンの主な生物学的活性は、キナーゼへのATP結合阻止によるプロテインキナーゼの阻害であり、これは、キナーゼのATP結合部位に対するスタウロスポリンの強力な親和性によって達成される。スタウロスポリンは、選択性は低いが、多くのキナーゼに高親和性で結合するという点で、典型的なATP競合キナーゼ阻害剤である。特異性の欠如によりその臨床使用が妨げられてきたが、スタウロスポリンを使用してアポトーシスを誘導する貴重な研究ツールとなっている。スタウロスポリンがアポトーシスを誘導する1つの経路はカスパーゼ−3の活性化によるものである。PAC−1及びスタウロスポリンによるU−937リンパ腫細胞の併用処置は、低PAC−1濃度(例えば、7.5μMと15μMのPAC−1)で相乗効果を示した(Figure4)。
ドキソルビシンは、DNA挿入によってその細胞毒性活性を作動させるアントラサイクリン系抗生物質である。ドキソルビシンは、血液悪性腫瘍、多くのタイプの癌腫、並びに軟部肉腫及び骨肉腫を含む、広範囲の癌の治療に使用されている。相乗的な活性は、PAC−1及びドキソルビシンによる143B(ヒトOS)骨肉腫細胞の組み合わせ処置に関して確認された(Figure5)。
タモキシフェンは、エストロゲン受容体の競合的作動薬であって、男性乳癌の最も一般的な治療法であり、初期ER+乳癌及び進行性ER+乳癌の両方で使用されている。タモキシフェンは、高リスクの患者の乳癌予防について承認されている。タモキシフェン及びPAC−1の組み合わせは相乗的であり、タモキシフェン陰性若しくはタモキシフェン耐性乳癌及びトリプルネガティブ乳癌を含む乳癌において細胞致死効率を高める(Figure6〜8)。
シスプラチンは、癌化学療法で使用されているいくつかの白金配位錯体の1種である。白金化合物の細胞毒性は癌細胞のDNA合成の阻害に起因し得る。シスプラチンは、肉腫、癌腫(肺小細胞癌及び卵巣癌を含む)、リンパ腫、胚細胞腫瘍及び精巣癌を含む種々のタイプの癌の処置で使用されている。シスプラチン及びPAC−1の組み合わせは相乗的であり、卵巣癌の場合と同様にこれらの処置における細胞致死効率を高め得る(Figure9)。
パクリタキセルは有糸分裂阻害剤(微小管安定剤)であって、肺癌、卵巣癌、乳癌及び頭頸部癌の処置で使用されている。パクリタキセルは、アントラサイクリン系が奏功しなかった後の進行性乳癌の処置に推奨されており、早期リンパ節陽性乳癌での使用が推奨されている。パクリタキセル及びPAC−1の組み合わせは相乗的な活性をもたらし、卵巣癌の場合と同様にこれらの処置における細胞致死効率を高める(Figure10)。
カルボプラチンは、癌化学療法で使用されているいくつかの白金配位錯体のうちの他の1種である。カルボプラチンは、種々のタイプの癌、主として卵巣癌、肺癌、頭頸部癌の処置で使用されている。カルボプラチン及びPAC−1の組み合わせは相乗的であり、骨肉腫の場合と同様にこれらの処置における細胞致死効率を高め得る(Figure11及び12)。
近年定義された17種の乳癌亜型のうちの12種を示す細胞株(表1)を利用して、標準治療薬のPAC−1感作/相乗作用についての非致死量の試験が進められている。
本発明は、癌細胞におけるアポトーシスを選択的に誘導する方法であって、癌細胞のプロカスパーゼ−3分子を修飾可能な化合物の組み合わせを癌細胞に投与するステップを含み、化合物の組み合わせはPAC−1及び第2の活性薬物である、方法を提供する。また、癌細胞におけるアポトーシスを選択的に誘導する方法であって、癌細胞のプロカスパーゼ−3分子を修飾可能な化合物の組み合わせを癌細胞に投与するステップを含み、化合物の組み合わせはPAC−1及び第2の活性薬物であり、例えば、癌細胞は処置の必要な患者体内にある、方法を提供する。
本明細書に記載の化合物を使用して、例えば、該化合物を薬学的に許容可能な希釈剤、賦形剤又は担体と組み合わせることによって、治療用医薬組成物を製造することができる。化合物は、塩又は溶媒和物の形態で担体に添加することができる。例えば、化合物が安定な非毒性の酸又は塩基の塩を形成するのに十分に塩基性又は酸性である場合、塩としての化合物の投与は適切であり得る。薬学的に許容可能な塩の例は、生理学的に許容可能な陰イオンを形成する酸と共に形成される有機酸付加塩であり、例えば、トシル酸塩、メタンスルホン酸塩、酢酸塩、クエン酸塩、マロン酸塩、酒石酸塩、コハク酸塩、安息香酸塩、アスコルビン酸塩、α−ケトグルタル酸塩、及びβ−グリセロリン酸塩である。さらに、適切な無機塩、例えば、塩酸塩、ハロゲン化物、硫酸塩、硝酸塩、重炭酸塩、及び炭酸塩の塩も形成され得る。
以下の製剤は、本明細書に記載の組み合わせ化合物(例えば、PAC−1及び第2の活性薬物)又はその薬学的に許容可能な塩若しくは溶媒和物(以下「化合物X」という。)を治療的又は予防的に投与するために使用され得る代表的な医薬剤形を示す。
化合物X 200.0
ラクトース 77.5
ポビドン 15.0
クロスカルメロースナトリウム 12.0
微結晶性セルロース 92.5
ステアリン酸マグネシウム 3.0
400.0
化合物X 120.0
微結晶性セルロース 410.0
デンプン 50.0
デンプングリコール酸ナトリウム 15.0
ステアリン酸マグネシウム 5.0
600.0
化合物X 110.0
コロイド状二酸化ケイ素 1.5
ラクトース 465.5
α化デンプン 120.0
ステアリン酸マグネシウム 3.0
700.0
化合物X 1.0
二塩基性リン酸水素ナトリウム 12.0
一塩基性リン酸ナトリウム 0.7
塩化ナトリウム 4.5
1.0N水酸化ナトリウム溶液 q.s.(7.0〜7.5にpH調整)
注射用蒸留水 q.s.ad 1mL
化合物X 10.0
一塩基性リン酸ナトリウム 0.3
二塩基性リン酸ナトリウム 1.1
ポリエチレングリコール400 200.0
0.1N水酸化ナトリウム溶液 q.s.(7.0〜7.5にpH調整)
注射用蒸留水 q.s.ad 1mL
化合物X 20
オレイン酸 10
トリクロロモノフルオロメタン 5000
ジクロロジフルオロメタン 10000
ジクロロテトラフルオロエタン 5000
Claims (28)
- (a)化合物PAC−1:
と、
(b)エトポシド、ボルテゾミブ、スタウロスポリン、ドキソルビシン、タモキシフェン、シスプラチン、カルボプラチン又はパクリタキセルである第2の活性薬物と、
(c)薬学的に許容可能な希釈剤、賦形剤又は担体と、
を含む組成物。 - 担体は水を含み、任意選択で、緩衝液、シクロデキストリン又はそれらの組み合わせをさらに含む、請求項1に記載の組成物。
- シクロデキストリンは2−ヒドロキシプロピル−β−シクロデキストリンである、請求項2に記載の組成物。
- PAC−1の濃度が約2μM〜約50μMである、請求項1に記載の組成物。
- 第2の活性薬物の濃度が約25nM〜約1mMである、請求項1に記載の組成物。
- 第2の活性薬物はエトポシドであり、エトポシドの濃度が約2μM〜約50μMである、請求項1又は4に記載の組成物。
- 第2の活性薬物はボルテゾミブであり、ボルテゾミブの濃度が約50nM〜約20μMである、請求項1又は4に記載の組成物。
- 第2の活性薬物はスタウロスポリンであり、スタウロスポリンの濃度が約25nM〜約200nMである、請求項1又は4に記載の組成物。
- 第2の活性薬物はドキソルビシンであり、ドキソルビシンの濃度が約50nM〜約5μMである、請求項1又は4に記載の組成物。
- 第2の活性薬物はタモキシフェンであり、タモキシフェンの濃度が約5μM〜約50μMである、請求項1又は4に記載の組成物。
- 第2の活性薬物はシスプラチンであり、シスプラチンの濃度が約5μM〜約150μMであり、第2の活性薬物はカルボプラチンであり、カルボプラチンの濃度が約5μM〜約150μMである、請求項1又は4に記載の組成物。
- 第2の活性薬物はパクリタキセルであり、パクリタキセルの濃度が約0.5nM〜約5nMである、請求項1又は4に記載の組成物。
- 癌細胞の成長又は増殖を抑制する方法であって、癌細胞を有効量の請求項1に記載の組成物と接触させ、それにより癌細胞の成長又は増殖を抑制するステップを含む方法。
- 癌細胞はリンパ腫細胞、骨肉腫細胞、乳癌細胞又は卵巣癌細胞である、請求項13に記載の方法。
- 癌細胞におけるアポトーシスを誘導する方法であって、
癌細胞を、有効量の化合物PAC−1:
及び有効量の第2の活性薬物と接触させるステップを含み、
第2の活性薬物は、エトポシド、ボルテゾミブ、スタウロスポリン、ドキソルビシン、タモキシフェン、シスプラチン、カルボプラチン又はパクリタキセルであり、
アポトーシスはそれにより癌細胞において誘導される、
方法。 - 前記接触はインビトロでの接触である、請求項15に記載の方法。
- 前記接触はインビボでの接触である、請求項15に記載の方法。
- 癌細胞をPAC−1及び第2の活性薬物と同時に接触させる、請求項15〜17のいずれか一項に記載の方法。
- 癌細胞を第2の活性薬物と接触させる前に癌細胞をPAC−1と接触させる、請求項15〜17のいずれか一項に記載の方法。
- 癌細胞を第2の活性薬物と接触させた後に癌細胞をPAC−1と接触させる、請求項15〜17のいずれか一項に記載の方法。
- 処置の必要な患者における癌を処置する方法であって、
患者に、治療有効量の化合物PAC−1:
及び有効量の第2の活性薬物を同時又は逐次に投与するステップを含み、
第2の活性薬物は、エトポシド、ボルテゾミブ、スタウロスポリン、ドキソルビシン、タモキシフェン、シスプラチン、カルボプラチン又はパクリタキセルであり、
癌はそれにより処置される、
方法。 - 化合物PAC−1及び第2の活性薬物は同時に投与される、請求項21に記載の方法。
- 化合物PAC−1及び第2の活性薬物は逐次に投与される、請求項21に記載の方法。
- 化合物PAC−1は第2の活性薬物の前に投与される、請求項23に記載の方法。
- 化合物PAC−1は第2の活性薬物の後に投与される、請求項23に記載の方法。
- 癌はリンパ腫、骨肉腫又は乳癌である、請求項21〜25のいずれか一項に記載の方法。
- 癌の処置のための医薬を調製するための、請求項1〜10のいずれか一項に記載の組成物の使用。
- 癌はリンパ腫、骨肉腫、乳癌又は卵巣癌である、請求項27に記載の使用。
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---|---|---|---|---|
KR20170022065A (ko) * | 2015-08-19 | 2017-03-02 | 한국과학기술연구원 | Pac-1을 이용한 단백질 발현 조절 시스템과 방법 및 pac-1을 유효성분 포함하는 독시사이클린 길항제 |
JP2018516936A (ja) * | 2015-06-05 | 2018-06-28 | ザ ボード オブ トラスティーズ オブ ザ ユニバーシテイ オブ イリノイ | Pac−1併用療法 |
JP2021503457A (ja) * | 2017-11-17 | 2021-02-12 | ザ ボード オブ トラスティーズ オブ ザ ユニバーシテイ オブ イリノイ | 二元的なmekシグナル伝達の低減によるがん治療 |
JP2022504184A (ja) * | 2018-10-05 | 2022-01-13 | ザ ボード オブ トラスティーズ オブ ザ ユニバーシテイ オブ イリノイ | ブドウ膜黒色腫の治療のための併用療法 |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008134474A2 (en) * | 2007-04-27 | 2008-11-06 | The Board Of Trustees Of The University Of Illinois | Compositions and methods including cell death inducers and procaspase activation |
IN2014MN01945A (ja) * | 2012-03-06 | 2015-07-10 | Univ Illinois | |
AU2014344789B2 (en) * | 2013-11-01 | 2019-10-03 | Pitney Pharmaceuticals Pty Limited | Pharmaceutical combinations for the treatment of cancer |
EP3227437A4 (en) | 2014-12-05 | 2018-08-22 | An2H Discovery Limited | Parkin ligase activation methods and compositions |
US10308617B2 (en) | 2016-06-03 | 2019-06-04 | An2H Discovery Limited | Triazole benzamide derivatives and the compositions and methods of treatment regarding the same |
US10889553B2 (en) | 2017-12-01 | 2021-01-12 | Nysnobio Ireland Dac | Asymmetric triazole benzamide derivatives and the compositions and methods of treatment regarding the same |
EP3976062A4 (en) * | 2019-05-30 | 2023-06-14 | The Board Of Trustees Of The University Of Illinois | PROCASPASE-3 ACTIVATION AND IMMUNOTHERAPY FOR THE TREATMENT OF CANCER |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007513962A (ja) * | 2003-12-09 | 2007-05-31 | アメリカ合衆国 | 免疫応答を抑制するため、または増殖性障害を治療するための方法 |
JP2008545718A (ja) * | 2005-05-26 | 2008-12-18 | ザ ボード オブ トラスティーズ オブ ザ ユニヴァーシティー オブ イリノイ | プロカスパーゼ−3の活性化を含む、癌細胞における選択的アポトーシス誘導 |
WO2010032440A1 (ja) * | 2008-09-17 | 2010-03-25 | 株式会社アドバンテスト | 試験装置およびドメイン間同期方法 |
Family Cites Families (39)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US597287A (en) | 1898-01-11 | Bicycle attachment | ||
US5723459A (en) * | 1991-05-09 | 1998-03-03 | Vertex Pharmaceuticals Incorporated | Biologically active acylated amino acid derivatives |
US5844001A (en) * | 1993-02-26 | 1998-12-01 | Research Development Foundation | Combination platinum chemotherapeutic/antiestrogen therapy for human cancers |
US6403765B1 (en) | 1998-06-16 | 2002-06-11 | Thomas Jefferson University | Truncated Apaf-1 and methods of use thereof |
US6303329B1 (en) | 1998-07-27 | 2001-10-16 | Pharmacia & Upjohn Company | Method for autoactivation of procaspase 8 |
US6110691A (en) | 2000-01-06 | 2000-08-29 | Board Of Regents, The University Of Texas System | Activators of caspases |
US6608026B1 (en) * | 2000-08-23 | 2003-08-19 | Board Of Regents, The University Of Texas System | Apoptotic compounds |
US20030008015A1 (en) | 2000-10-11 | 2003-01-09 | Levisage Catherine S. | Polymer controlled delivery of a therapeutic agent |
WO2002048329A2 (en) | 2000-11-20 | 2002-06-20 | Idun Pharmaceuticals, Inc. | Membrane derived caspase-3, compositions comprising the same and methods of use therefor |
DE10128840A1 (de) * | 2001-06-15 | 2003-01-09 | Otis Elevator Co | Verfahren und Vorrichtung zur Steuerung des Antriebs einer Fördereinrichtung |
WO2003024955A2 (en) | 2001-09-18 | 2003-03-27 | Sunesis Pharmaceuticals, Inc. | Small molecule inhibitors of caspases |
US6702122B2 (en) * | 2002-07-11 | 2004-03-09 | Frank G. Hopkins | Rack for fork lift extensions |
WO2004066958A2 (en) | 2003-01-30 | 2004-08-12 | The Trustees Of Princeton University | Caspase-9:bir3 domain of xiap complexes and methods of use |
US7632972B2 (en) | 2003-10-30 | 2009-12-15 | The Board Of Trustees Of The University Of Illionis | Compounds and methods for treatment of cancer and modulation of programmed cell death for melanoma and other cancer cells |
BRPI0609957A2 (pt) * | 2005-05-12 | 2010-05-11 | Pfizer | uso de malato de sunitinib na preparação de um medicamento para o tratamento de cáncer |
WO2008134474A2 (en) * | 2007-04-27 | 2008-11-06 | The Board Of Trustees Of The University Of Illinois | Compositions and methods including cell death inducers and procaspase activation |
CN101184491A (zh) * | 2005-05-26 | 2008-05-21 | 伊利诺伊大学评议会 | 包括活化半胱天冬酶-3酶原的癌细胞内选择性细胞凋亡诱导 |
JP4119478B1 (ja) | 2005-06-23 | 2008-07-16 | メルク エンド カムパニー インコーポレーテッド | チロシンキナーゼインヒビター |
TWI373473B (en) | 2005-09-02 | 2012-10-01 | Otsuka Pharma Co Ltd | Anticancer agent |
PL1937252T3 (pl) * | 2005-09-19 | 2018-01-31 | Neuronascent Inc | Kompozycje do stymulowania neurogenezy oraz hamowania degeneracji neuronów |
PE20071042A1 (es) * | 2005-11-04 | 2007-10-12 | Wyeth Corp | Producto farmaceutico que comprende temsirolimus y malato de sunitinib |
US20070111936A1 (en) | 2005-11-15 | 2007-05-17 | Vladimir Pak | Complex of alpha-fetoprotein and inducers of apoptosis for the treatment of cancer |
US7886969B2 (en) | 2005-12-06 | 2011-02-15 | Visa U.S.A. Inc. | Method and system for loading and reloading portable consumer devices |
US8778845B2 (en) * | 2005-12-15 | 2014-07-15 | Genral Electric Company | Composition, device and associated method |
BRPI0711769A2 (pt) | 2006-05-19 | 2011-12-13 | Univ Illinois | compostos contendo fósforo incluindo ésteres trifenilmetilfosfonato para o tratamento de melanoma e outros cánceres |
TWI433674B (zh) * | 2006-12-28 | 2014-04-11 | Infinity Discovery Inc | 環杷明(cyclopamine)類似物類 |
WO2009076170A2 (en) * | 2007-12-13 | 2009-06-18 | Novartis Ag | Combinations of therapeutic agents for treating cancer |
RU2360692C1 (ru) | 2007-12-21 | 2009-07-10 | Тихоокеанский Институт Биоорганической Химии Дальневосточного Отделения Российской Академии Наук (Тибох Дво Ран) | Средство, стимулирующее апоптоз клеток лейкемии человека |
EP2237784A1 (en) | 2008-01-11 | 2010-10-13 | The Regents of the University of California | Activators of executioner procaspases 3, 6 and 7 |
US8349353B2 (en) * | 2008-06-27 | 2013-01-08 | Otonomy, Inc. | Controlled release cytotoxic agent compositions and methods for the treatment of otic disorders |
US20100291214A1 (en) | 2008-12-23 | 2010-11-18 | Armark Authentication Technologies, Llc | Three-dimensional microfiber extrudate structure and process for forming three-dimensional microfiber extrudate structure |
CN106946812B (zh) * | 2009-02-09 | 2020-10-09 | 伊利诺伊大学评议会 | 作为个性化抗癌药的胱天蛋白酶原活化化合物的设计、合成和评价 |
CN102483419B (zh) * | 2009-05-11 | 2017-12-15 | 博格有限责任公司 | 利用表观代谢转变剂、多维细胞内分子或环境影响剂诊断代谢障碍的方法 |
WO2010138141A1 (en) * | 2009-05-27 | 2010-12-02 | Cephalon, Inc. | Combination therapy for the treatment of multiple myeloma |
WO2010151746A2 (en) * | 2009-06-26 | 2010-12-29 | Armark Authentication Technologies, Llc | Three-dimensional microfiber extrudate structure and process for forming three-dimensional microfiber extrudate structure |
JP5094797B2 (ja) | 2009-08-07 | 2012-12-12 | 日立オートモティブシステムズ株式会社 | 直流電源平滑用コンデンサーの放電回路 |
CN102085214A (zh) * | 2011-01-27 | 2011-06-08 | 范晓青 | 低分子柑橘果胶联和临床常用化疗药用于控制癌症和癌症转移扩散 |
IN2014MN01945A (ja) * | 2012-03-06 | 2015-07-10 | Univ Illinois | |
EP3302478B1 (en) * | 2015-06-05 | 2021-11-17 | The Board of Trustees of the University of Illinois | Pac-1 combination therapy |
-
2013
- 2013-03-06 IN IN1945MUN2014 patent/IN2014MN01945A/en unknown
- 2013-03-06 RU RU2014139954A patent/RU2659936C2/ru active
- 2013-03-06 WO PCT/US2013/029405 patent/WO2013134407A2/en active Application Filing
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- 2022-01-07 WO PCT/US2022/011680 patent/WO2022150633A1/en unknown
- 2022-01-07 EP EP22737203.4A patent/EP4274558A1/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007513962A (ja) * | 2003-12-09 | 2007-05-31 | アメリカ合衆国 | 免疫応答を抑制するため、または増殖性障害を治療するための方法 |
JP2008545718A (ja) * | 2005-05-26 | 2008-12-18 | ザ ボード オブ トラスティーズ オブ ザ ユニヴァーシティー オブ イリノイ | プロカスパーゼ−3の活性化を含む、癌細胞における選択的アポトーシス誘導 |
WO2010032440A1 (ja) * | 2008-09-17 | 2010-03-25 | 株式会社アドバンテスト | 試験装置およびドメイン間同期方法 |
Non-Patent Citations (1)
Title |
---|
改訂 医薬品添加物ハンドブック HANDBOOK OF PHARMACEUTICAL EXCIPIENTS, vol. Fifth Edition, JPN6016040641, 28 February 2007 (2007-02-28), pages 400-406 * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2018516936A (ja) * | 2015-06-05 | 2018-06-28 | ザ ボード オブ トラスティーズ オブ ザ ユニバーシテイ オブ イリノイ | Pac−1併用療法 |
JP7033451B2 (ja) | 2015-06-05 | 2022-03-10 | ザ ボード オブ トラスティーズ オブ ザ ユニバーシテイ オブ イリノイ | Pac-1併用療法 |
KR20170022065A (ko) * | 2015-08-19 | 2017-03-02 | 한국과학기술연구원 | Pac-1을 이용한 단백질 발현 조절 시스템과 방법 및 pac-1을 유효성분 포함하는 독시사이클린 길항제 |
JP2021503457A (ja) * | 2017-11-17 | 2021-02-12 | ザ ボード オブ トラスティーズ オブ ザ ユニバーシテイ オブ イリノイ | 二元的なmekシグナル伝達の低減によるがん治療 |
US11510919B2 (en) | 2017-11-17 | 2022-11-29 | The Board Of Trustees Of The University Of Illinois | Cancer therapy by degrading dual MEK signaling |
JP7349155B2 (ja) | 2017-11-17 | 2023-09-22 | ザ ボード オブ トラスティーズ オブ ザ ユニバーシテイ オブ イリノイ | 二元的なmekシグナル伝達の低減によるがん治療 |
JP2022504184A (ja) * | 2018-10-05 | 2022-01-13 | ザ ボード オブ トラスティーズ オブ ザ ユニバーシテイ オブ イリノイ | ブドウ膜黒色腫の治療のための併用療法 |
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