JP2021521169A - リン脂質−フラバグリン複合体およびそれを標的癌治療に使用する方法 - Google Patents
リン脂質−フラバグリン複合体およびそれを標的癌治療に使用する方法 Download PDFInfo
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- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
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- 238000003786 synthesis reaction Methods 0.000 description 1
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- 229940095064 tartrate Drugs 0.000 description 1
- 210000001138 tear Anatomy 0.000 description 1
- GZCRRIHWUXGPOV-UHFFFAOYSA-N terbium atom Chemical compound [Tb] GZCRRIHWUXGPOV-UHFFFAOYSA-N 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- NBAOBNBFGNQAEJ-UHFFFAOYSA-M tetramethylrhodamine ethyl ester perchlorate Chemical compound [O-]Cl(=O)(=O)=O.CCOC(=O)C1=CC=CC=C1C1=C2C=CC(=[N+](C)C)C=C2OC2=CC(N(C)C)=CC=C21 NBAOBNBFGNQAEJ-UHFFFAOYSA-M 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
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- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 125000000464 thioxo group Chemical group S=* 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 231100000155 toxicity by organ Toxicity 0.000 description 1
- 230000007675 toxicity by organ Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 229940066528 trichloroacetate Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000000725 trifluoropropyl group Chemical group [H]C([H])(*)C([H])([H])C(F)(F)F 0.000 description 1
- 125000005455 trithianyl group Chemical group 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 231100000925 very toxic Toxicity 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000001018 xanthene dye Substances 0.000 description 1
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
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Abstract
Description
この出願は、2018年4月10日に出願された米国仮特許出願第62/655,659号の優先権を主張し、その全体が参照により本明細書に組み込まれる。
リン脂質化合物およびリン脂質−フラバグリン複合体を、本明細書に説明する。正常組織よりも高い濃度の天然由来のエーテル脂質を含む多数の動物およびヒトの腫瘍に基づいて、リン脂質エーテル(PLE)分子が開発されてきた。本明細書に詳述されるPLE分子は、腫瘍および癌細胞に薬物を選択的に送達する腫瘍標的化の基盤として使用できる。
1.定義
2.エーテル型リン脂質
3.リン脂質−フラバグリン複合体
a.合成
4.医薬組成物
5.投与
6.方法
a.対象の癌を治療する方法
b.対象の腫瘍または癌細胞に薬物を標的化する方法
7.実施例
実施例1
化学合成
実施例3
腫瘍細胞中へのPDCの選択的取込み
実施例4
脂質ラフトの破壊によりPDCの取込みが低減した
実施例5
PDCは小胞体まで追跡する
実施例6
PDCは小胞体まで追跡する
実施例7
PDCは生体内で標的化送達を提供する
実施例8
細胞毒性PDCは、標的化および治療指数の潜在的な向上を提供する
実施例9
細胞毒性PDCは標的化を提供する
実施例10
PLEの細胞取込み
Claims (18)
- 請求項1または2に記載のPLEであって、それに結合した検出可能な部分をさらに含む、PLE。
- 請求項1または2または3に記載のPLEおよび担体を含む組成物。
- 請求項5に記載の化合物および担体を含む組成物。
- 前記フラバグリン抗癌剤は、FLV-1、FLV-3、それらの誘導体もしくは類似体、またはそれらの組合せを含む、請求項7に記載の複合体。
- 請求項7〜10のいずれか1項に記載の複合体および薬学的に許容される担体を含む組成物。
- 請求項7〜10のいずれか1項に記載の複合体を対象に投与することを含む、対象の癌を治療する方法。
- 請求項7〜10のいずれか1項に記載の複合体を対象に投与することを含む、対象の腫瘍または癌細胞に薬物を標的化する方法。
- 前記フラバグリン抗癌剤が、前記腫瘍または癌細胞の細胞質または細胞小器官に局在または移動する、請求項12または13に記載の方法。
- 前記複合体またはフラバグリン抗癌剤が、前記対象の癌細胞に対して選択的である、請求項12または13に記載の方法。
- 前記複合体またはフラバグリン抗癌剤が、健康な細胞より少なくとも約2倍多く腫瘍または癌細胞中に取り込まれる、請求項12または13に記載の方法。
- 前記癌が、黒色腫、脳腫瘍、肺がん、副腎がん、肝臓がん、腎臓がん、膵臓がん、食道がん、胃がん、結腸がん、大腸がん、肛門がん、前立腺がん、卵巣がん、乳がん、子宮頸がん、リンパ腫、白血病、骨髄腫、血液がん、肝がん、網膜芽細胞腫、神経膠腫、肉腫、芽細胞腫、扁平上皮がん、および腺がんから選択される、請求項12〜16のいずれか1項に記載の方法。
- 前記対象がヒトである、請求項12〜17のいずれか1項に記載の方法。
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US201862655659P | 2018-04-10 | 2018-04-10 | |
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PCT/US2019/026853 WO2019200017A1 (en) | 2018-04-10 | 2019-04-10 | Phospholipid-flavagline conjugates and methods of using the same for targeted cancer therapy |
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AU2020346898A1 (en) * | 2019-09-12 | 2022-04-07 | Cellectar Biosciences, Inc. | Phospholipid ether conjugates as cancer-targeting drug vehicles |
Citations (3)
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JPH06263643A (ja) * | 1991-09-27 | 1994-09-20 | Max Planck Ges Foerderung Wissenschaft Ev | 原生動物感染症の治療時の経口又は局所投与用薬剤の製造方法 |
DE4408011C1 (de) * | 1994-03-10 | 1995-11-02 | Max Delbrueck Centrum | Pharmazeutisches Mittel zur Tumortherapie |
WO2017218702A1 (en) * | 2016-06-14 | 2017-12-21 | Cellectar Biosciences, Inc. | Phospholipid ether analogs for the identification and isolation of circulating tumor cells |
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WO2008150439A1 (en) | 2007-06-01 | 2008-12-11 | Cellectar, Inc. | Compositions of phospholipid ether boronic acids and esters and methods for their synthesis and use |
CN103944903B (zh) | 2014-04-23 | 2017-02-15 | 福建联迪商用设备有限公司 | 一种多方授权的apk签名方法及系统 |
PT3229810T (pt) | 2014-11-17 | 2020-08-27 | Cellectar Biosciences Inc | Análogos de éter fosfolipídico como veículos de medicamentos direcionados para o cancro |
EP3464280B1 (en) * | 2016-06-06 | 2021-10-06 | F. Hoffmann-La Roche AG | Silvestrol antibody-drug conjugates and methods of use |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06263643A (ja) * | 1991-09-27 | 1994-09-20 | Max Planck Ges Foerderung Wissenschaft Ev | 原生動物感染症の治療時の経口又は局所投与用薬剤の製造方法 |
DE4408011C1 (de) * | 1994-03-10 | 1995-11-02 | Max Delbrueck Centrum | Pharmazeutisches Mittel zur Tumortherapie |
WO2017218702A1 (en) * | 2016-06-14 | 2017-12-21 | Cellectar Biosciences, Inc. | Phospholipid ether analogs for the identification and isolation of circulating tumor cells |
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AU2019251483A1 (en) | 2020-10-15 |
EP3773544A1 (en) | 2021-02-17 |
CN112272556A (zh) | 2021-01-26 |
CN112272556B (zh) | 2023-12-19 |
EA202092369A1 (ru) | 2021-01-26 |
IL304245A (en) | 2023-09-01 |
CA3095515A1 (en) | 2019-10-17 |
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