ABT-751 (E7010)

ABT-751 (E7010) binds to the colchicine site on β-tubulin and inhibits polymerization of microtubules, not a substrate for the MDR transporter and is active against cell lines resistant to vincristine, doxorubicin, and cisplatin. Phase 1/2.

CAS No. 141430-65-1

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 28500	国内在庫あり
10mg	JPY 21900	国内在庫あり
50mg	JPY 80000	国内在庫あり

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（5）

カスタマーフィードバック3个实验数据

製品安全説明書

現在のバッチを見る： S116501 DMSO] 74 mg/mL] false] Ethanol] 12 mg/mL] false] Water] Insoluble] false 純度： 99.95%

99.95

ABT-751 (E7010)関連製品

関連化合物ライブラリー	Kinase Inhibitor Library Angiogenesis Related compound Library TGF-beta/Smad compound library Cytoskeletal Signaling Pathway Compound Library Anti-Cardiovascular Disease Compound Library	もっと見る

シグナル伝達経路

Microtubule Associatedシグナル伝達経路

Microtubule Associated阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
HUVEC	Function assay	100-1000 nM	4 h	Induction of vascular disrupting activity in HUVEC assessed as VEGF-induced tube formation at 100 to 1000 nM after 4 hrs by microscopic analysis	24106982
P388 cell line	Function assay		72 h	Effective concentration to inhibit cell proliferation by 50% relative to untreated control cell after 72 hr of continuous exposure in P388 cell line， IC50=0.19 μM	12383017
P388/4.0 r-M cell line	Function assay		72 h	Effective concentration to inhibit cell proliferation by 50% relative to untreated control cell after 72 hr of continuous exposure in P388/4.0 r-M cell line, IC50=15 μM	12383017
HeLa cells	Cytotoxicity assay		48-72 h	Cytotoxicity against human HeLa cells after 48 to 72 hrs by WAT-1 assay, IC50=0.27 μM	21126027
MDR1 cells	Cytotoxicity assay		48-72 h	Cytotoxicity against human NCI-ADR-RES expressing MDR1 cells after 48 to 72 hrs by WAT-1 assay, IC50=0.29 μM	21126027
Jurkat cells	Function assay		24 h	Cell cycle arrest in human Jurkat cells assessed as accumulation at G2/M phase after 24 hrs using propidium iodide staining by FACS analysis, IC50=0.16 μM	21126027
SW620 cells	Cytotoxicity assay		48-72 h	Cytotoxicity against human SW620 cells after 48 to 72 hrs by WAT-1 assay, IC50=0.19 μM	21126027
A2780 cells	Cytotoxicity assay		48-72 h	Cytotoxicity against human A2780 cells after 48 to 72 hrs by WAT-1 assay, IC50=0.17 μM	21126027
HT-29 cells	Proliferation assay		72 h	Antiproliferative activity against human HT-29 cells after 72 hrs by MTT assay, IC50=0.21 μM	23202849
H460 cells	Cytotoxicity assay		72 h	Cytotoxicity against human H460 cells assessed as growth inhibition after 72 hrs by methylene blue staining-based assay, IC50=0.2177 μM	24106982
MKN45 cells	Cytotoxicity assay		72 h	Cytotoxicity against human MKN45 cells assessed as growth inhibition after 72 hrs by methylene blue staining-based assay, IC50=0.166 μM	24106982
HT-29 cells	Cytotoxicity assay		72 h	Cytotoxicity against human HT-29 cells assessed as growth inhibition after 72 hrs by methylene blue staining-based assay, IC50=0.3387 μM	24106982
human A549 cells	Cytotoxicity assay		48 h	Cytotoxicity against human A549 cells after 48 hrs by MTT assay, IC50=1.31 μM	24835786
ACHN cells	Cytotoxicity assay		48 h	Cytotoxicity against human ACHN cells after 48 hrs by MTT assay, IC50=2.13 μM	24835786
MCF7 cells	Cytotoxicity assay		48 h	Cytotoxicity against human MCF7 cells after 48 hrs by MTT assay, IC50=1.25 μM	24835786
HT-29 cells	Cytotoxicity assay		48 h	Cytotoxicity against human HT-29 cells after 48 hrs by MTT assay, IC50=1.62 μM	24835786
A549 cells	Proliferation assay		24 h	Antiproliferative activity against human A549 cells assessed as growth inhibition after 24 hrs by SRB assay, GI50=1.31 μM	25468039
human MCF7 cells	Proliferation assay		24 h	Antiproliferative activity against human MCF7 cells assessed as growth inhibition after 24 hrs by SRB assay, GI50=1.25 μM	25468039
KB-S15 cells	Cytotoxicity assay		72 h	Cytotoxicity against human KB-S15 cells overexpressing P-gp170/MDR assessed as growth inhibition after 72 hrs by methylene blue staining-based assay, IC50=0.206 μM	24106982
KB-7d cells	Cytotoxicity assay		72 h	Cytotoxicity against human KB-7d cells overexpressing MRP assessed as growth inhibition after 72 hrs by methylene blue staining-based assay, IC50=0.205 μM	24106982
KB-VIN10 cells	Cytotoxicity assay		72 h	Cytotoxicity against human KB-VIN10 cells overexpressing P-gp170/MDR assessed as growth inhibition after 72 hrs by methylene blue staining-based assay, IC50=0.227 μM	24106982
human PC3 cells	Cytotoxicity assay		48 h	Cytotoxicity against human PC3 cells assessed as growth inhibition after 48 hrs by sulforhodamine B assay, GI50=0.62 μM	26241032
human AsPC1 cells	Cytotoxicity assay		48 h	Cytotoxicity against human AsPC1 cells assessed as growth inhibition after 48 hrs by sulforhodamine B assay, GI50=4.11 μM	26241032
human A549 cells	Cytotoxicity assay		48 h	Cytotoxicity against human A549 cells assessed as growth inhibition after 48 hrs by sulforhodamine B assay, GI50=5.33 μM	26241032
Hep3B cells	Cytotoxicity assay		48 h	Cytotoxicity against human Hep3B cells assessed as growth inhibition after 48 hrs by sulforhodamine B assay, GI50=0.84 μM	26241032
KB cells	Cytotoxicity assay		72 h	Cytotoxicity against human KB cells assessed as growth inhibition after 72 hrs by methylene blue staining-based assay, IC50=0.2513 μM	24106982
DU145 cells	Proliferation assay		24 h	Antiproliferative activity against human DU145 cells assessed as growth inhibition after 24 hrs by SRB assay, GI50=1.81 μM	25468039
DU145 cells	Cytotoxicity assay		48 h	Cytotoxicity against human DU145 cells after 48 hrs by MTT assay， GI50=1.81 μM	24835786
human SKBR3 cells	Growth inhibition assay		48 h	Growth inhibition of human SKBR3 cells after 48 hrs by MTT assay, IC50=0.74 μM	22850214
HCT-15 cell	Proliferation assay			Antiproliferative activity against human colon carcinoma HCT-15 cell line(MDR(-)), IC50=0.34 μM	11425534
HCT116-C9 cell	Function assay			Effective concentration to inhibit cell proliferation by 50% relative to untreated control cell after 72 hr of continuous exposure in HCT116-C9 cell line, IC50=0.9 μM	12383017
NCI-H460 cell	Proliferation assay			Antiproliferative activity against human lung carcinoma NCI-H460 cell line (MDR(+)), IC50=0.35 μM	11425534
human HL60 cells	Proliferation assay			Antiproliferative activity against human HL60 cells, IC50=0.34 μM	17276056
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

ABT-751 (E7010) binds to the colchicine site on β-tubulin and inhibits polymerization of microtubules, not a substrate for the MDR transporter and is active against cell lines resistant to vincristine, doxorubicin, and cisplatin. Phase 1/2.

特性

An orally bioavailable tubulin-binding and antimitotic sulfonamide.

Targets

Microtubules ^[1]

In Vitro
In vitro	In vitro, ABT-751 shows the selective cytotoxicity with IC50 of 0.6–2.6 μM in neuroblastoma and 0.7–4.6 μM in other solid tumor cell lines. Furthermore, ABT-751 also exhibits a selective effect on dynamic microtubules and spares stable microtubules, accounting for the persistence of acetylated and detyrosinated α-tubulin positive polymerized tubules at the IC90 concentration of ABT-751. ^[1]
細胞実験	細胞株	HOS, HTB-186 Daoy, TC-71, RD, SK-N-AS, SK-N-DZ, LD and KCNR cells
	濃度	0 to 100 μM
	反応時間	72 hours
	実験の流れ	Cells, in 1640 RPMI media with FBS, are plated in triplicate onto 96 well tissue culture plates in numbers determined optimal for confluent monolayer growth (5,000 cells/well for HOS, HTB-186 Daoy; 10,000 cells/well for TC-71, RD, SK-N-AS, SK-N-DZ, LD; 30,000 cells/well for KCNR), with an automated, multichannel pipette system. Cells are incubated for 24 hours at 37 °C/5% CO₂ then exposed to vehicle control (1.25% DMSO/H₂O), VCR (0.1–1000 nM), ABT-751 (0.1 nM–100 μM), and in 4 cell lines (SK-N-AS, KCNR, RD, TC-71) combretastatin (0.1–1000 nM) for 72 hours. Cells are fixed with trichloroacetic acid (final concentration 10%) at 4 °C, washed, then dried at room temperature, stained with SRB in 1% acetic acid and dye is then solubilized with Tris base. Optical density measurements are performed at 540 and 405 nm dual wavelengths in a Bio-Tek EL 340 UV plate reader.

In Vivo
In Vivo	In this Calu-6 xenograft model, ABT-751 as a single agent at 100 and 75 mg/kg/day shows significant antitumor activity, while in combination with cisplatin, ABT-751 shows a dose-dependent enhancement in growth delay. In the HT-29 colon xenograft model, ABT-751 also shows significant antitumor activity as a single agent and produced a dose-dependent enhancement in growth delay In combination with 5-FU. ^[2] In dogs with lymphoma, ABT-751 exhibits the dose-limiting toxicities that included vomiting, diarrhea, anorexia, or some combination of these with a maximum tolerated dose (MTD) of 350 mg/m² PO q24h. Furthermore, the mean AUC and C_max for ABT-751 at the MTD of 350 mg/m² is 5.55 μg-hour/mL and 0.9 μg/mL, respectively. ^[3]
動物実験	動物モデル	Calu-6 NSCLC, HT-29 colon, and HCT-116 cells are injected into athymic mice.
	投与量	75 or 100 mg/kg/day
	投与経路	Administered via p.o.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT00436852	Completed	Disseminated Neuroblastoma\|Recurrent Neuroblastoma	Children''s Oncology Group\|National Cancer Institute (NCI)	January 2007	Phase 2
NCT00735878	Terminated	Non Small Cell Lung Cancer\|Lung Cancer	Konstantin Dragnev\|Abbott\|Dartmouth-Hitchcock Medical Center	September 2004	Phase 1\|Phase 2

参考
[1] Meany HJ, et al. Pediatr Blood Cancer. 2010, 54(1), 47-54. [2] Jorgensen TJ, et al. Cancer Chemother Pharmacol. 2007, 59(6), 725-732. [3] Silver M, et al. J Vet Intern Med. 2012, 26(2), 349-354.

参考

化学情報

分子量	371.41	化学式	C₁₈H₁₇N₃O₄S
CAS No.	141430-65-1	SDF	Download ABT-751 (E7010) SDFをダウンロードする
Smiles	COC1=CC=C(C=C1)S(=O)(=O)NC2=C(N=CC=C2)NC3=CC=C(C=C3)O
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 74 mg/mL ( (199.24 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 12 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):