Ispinesib (SB-715992)

別名:CK0238273

Ispinesib (SB-715992, CK0238273) is a potent, specific and reversible inhibitor of kinesin spindle protein (KSP) with Ki app of 1.7 nM in a cell-free assay, no inhibition to CENP-E, RabK6, MCAK, MKLP1, KHC or Kif1A. Ispinesib induces mitotic arrest and apoptotic cell death.

Ispinesib (SB-715992)化学構造

CAS No. 336113-53-2

サイズ 価格(税別) 在庫状況
10mM (1mL in DMSO) JPY 71700 国内在庫あり
JPY 18900 国内在庫あり
JPY 55100 国内在庫あり
JPY 163000 国内在庫あり

代表番号: 045-509-1970|電子メール:[email protected]
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文献中Selleckの製品使用例(26)

カスタマーフィードバック4个实验数据

製品安全説明書

現在のバッチを見る: 純度: 99.97%
99.97

Ispinesib (SB-715992)関連製品

シグナル伝達経路

Kinesin阻害剤の選択性比較

Cell Data

Cell Lines Assay Type Concentration Incubation Time 活性情報 PMID
LXFS 538 Antitumor assay 6 mg/kg Antitumor activity against human LXFS 538 cells xenografted in NMRI nu/nu mouse assessed as tumor regression at 6 mg/kg, ip measured on day 13 23394180
HCT116 Growth inhibition assay 72 hrs Growth inhibition of human HCT116 cells after 72 hrs by MTS assay, IC50=0.0011μM 26396688
MCF7 Antiproliferative assay 48 hrs Antiproliferative activity against human MCF7 cells after 48 hrs by MTT assay, IC50=1.3μM 24184776
HeLa Antiproliferative assay 48 hrs Antiproliferative activity against human HeLa cells after 48 hrs by MTT assay, IC50=1μM 24184776
NCI-H1299 Growth inhibition assay 72 hrs Growth inhibition of human NCI-H1299 cells after 72 hrs by Alamar blue assay, GI50=0.082μM 23394180
BxPC3 Growth inhibition assay 72 hrs Growth inhibition of human BxPC3 cells after 72 hrs by Alamar blue assay, GI50=0.08μM 23394180
PC3 Growth inhibition assay 72 hrs Growth inhibition of human PC3 cells after 72 hrs by Alamar blue assay, GI50=0.05μM 23394180
HCT116 Growth inhibition assay 72 hrs Growth inhibition of human HCT116 cells after 72 hrs by Alamar blue assay, GI50=0.025μM 23394180
LNCAP Growth inhibition assay 72 hrs Growth inhibition of human LNCAP cells after 72 hrs by Alamar blue assay, GI50=0.022μM 23394180
NCI-H1299 Antiproliferative assay 72 hrs Antiproliferative activity against human NCI-H1299 cells after 72 hrs by Alamar blue assay, GI50=0.082μM 22248262
BxPC3 Antiproliferative assay 72 hrs Antiproliferative activity against human BxPC3 cells after 72 hrs by Alamar blue assay, GI50=0.08μM 22248262
K562 Antiproliferative assay 72 hrs Antiproliferative activity against human K562 cells after 72 hrs by Alamar blue assay, GI50=0.071μM 22248262
hTERT-HME1 Antiproliferative assay 72 hrs Antiproliferative activity against human hTERT-HME1 cells after 72 hrs by Alamar blue assay, GI50=0.032μM 22248262
HCT116 Antiproliferative assay 72 hrs Antiproliferative activity against human HCT116 cells after 72 hrs by Alamar blue assay, GI50=0.025μM 22248262
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells 29435139
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells 29435139
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生物活性

製品説明 Ispinesib (SB-715992, CK0238273) is a potent, specific and reversible inhibitor of kinesin spindle protein (KSP) with Ki app of 1.7 nM in a cell-free assay, no inhibition to CENP-E, RabK6, MCAK, MKLP1, KHC or Kif1A. Ispinesib induces mitotic arrest and apoptotic cell death.
特性 An allosteric, potent, specific, and reversible inhibitor of the mitotic kinesin spindle protein (KSP) (HsEg5).
Targets
KSP (HsEg5) [1]
(Cell-free assay)
1.7 nM(Ki app)
In Vitro
In vitro

Ispinesib is a potent, allosteric, reversible, and specific inhibitor of KSP, which changes the binding property of KSP to microtubules and disturbs its movement by inhibiting ADP release without altering the release of the KSP-ADP complex from the microtubule. [1] Ispinesib shows potent cytotoxic activity in a panel of tumor cell lines, including Colo205, Colo201, HT-29, M5076, Madison-109, and MX-1, with IC50 of 1.2 nM to 9.5 nM. [2] In PC-3 prostate cancer cells, Ispinesib (15 nM and 30 nM) blocks cell proliferation and induces apoptosis by regulating the expression levels of genes that controls apoptosis, cell proliferation, cell cycle, and cell signaling, such as EGFR, p27, p15, and IL-11. [3] In a panel of 53 breast cell lines, Ispinesib (7.4 nM–600 nM) demonstrates broad inhibitory activity. In BT-474 and MDA-MB-468 cells, Ispinesib (150 nM) induces apoptosis, as revealed by a higher proportion of apoptotic cells, lower antiapoptotic Bcl-XL level, and higher proapoptotic Bax and Bid levels. [4]

Kinase Assay Steady-State Kinetic Analysis of Human KSP ATPase Activity and Inhibition by Ispinesib
Kinesin specificity analysis is carried out using a pyruvate kinase-lactate dehydrogenase detection system that couples the production of ADP to oxidation of NADH. Absorbance changes are monitored at 340 nm. Steady-state studies using nanomolar concentrations of KSP are performed using a sensitive fluorescence-based assay utilizing a pyruvate kinase, pyruvate oxidase, and horseradish peroxidase (HRP) coupled detection system that couples the generation of ADP to oxidation of Amplex Red to fluorescent resorufin. Generation of resorufin is monitored by fluorescence (λexcitation = 520 nm and λemission = 580 nm). Steady-state biochemical experiments are performed in PEM25 buffer [25 mM Pipes-K+ (pH 6.8), 2 mM MgCl2, 1 mM EGTA] supplemented with 10 µM paclitaxel for experiments involving microtubules. The IC50 for steady-state inhibition is determined at 500 µM ATP, 5 µM Microtubules, and 1 nM KSP in PEM25 buffer. Ki app (apparent inhibitor dissociation constant) values of Ispinesib are extracted from the dose-response curves, with explicit correction for enzyme concentration by using the Morrison equation.Inhibitor modality (e.g., competitive, noncompetitive, uncompetitive, or mixed) under steady-state conditions is determined by measuring the effect of inhibitor concentration on initial velocity as a function of substrate concentrations. Data are fit using equations in GraFit to velocity equations for the various modes of inhibition.
細胞実験 細胞株 Breast cancer cells, including MCF-7, HCC1954, MDA-MB-468, and KPL4
濃度 0.085 nM–33 µM
反応時間 72 hours
実験の流れ

Cells are plated in log phase of growth in 96-well plates and treated with Ispinesib for 72 hours. Then, cell growth is measured using CellTiter-Glo, and luminescence is detected using BioTek FLx800. Data are analyzed and the IC50 value, defined as the drug concentration that results in 50% growth inhibition relative to control, is calculated.

In Vivo
In Vivo

Ispinesib (4.5 mg/kg–15 mg/kg) exhibits inhibitory effects against Colo205, Colo201, HT-29, but not MX-1 cells, in mouse xenograft models. SB-715992 (6 mg/kg–10 mg/kg ) also inhibits murine solid tumors, including Madison 109 lung carcinoma, M5076 sarcoma, as well as L1210 and P388 leukemias. [2] In mice xenograft models of breast cancer cells MCF-7, HCC1954, MDA-MB-468, and KPL4, Ispinesib (8 mg/kg–10 mg/kg) inhibits tumor growth. [4]

動物実験 動物モデル Nude (nu/nu) mice models of MCF7, KPL4, and HCC1954 cells; severe combined immunodeficient (SCID) mice model of MDA-MB-468 cells;
投与量 10 mg/kg for nude mice or 8 mg/kg for SCID mice
投与経路 Intraperitoneal injection on a q4d× schedule (3 doses, every 4 day
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00607841 Terminated
Breast Neoplasms
Cytokinetics
December 2007 Phase 1
NCT00354250 Completed
Recurrent Renal Cell Cancer|Stage III Renal Cell Cancer|Stage IV Renal Cell Cancer
National Cancer Institute (NCI)
May 2006 Phase 2
NCT00097409 Completed
Ovarian Cancer
GlaxoSmithKline
December 2004 Phase 2
NCT00119171 Completed
Solid Tumor Cancer
GlaxoSmithKline
November 2004 Phase 1

化学情報

分子量 517.06 化学式

C30H33ClN4O2

CAS No. 336113-53-2 SDF Download Ispinesib (SB-715992) SDFをダウンロードする
Smiles CC1=CC=C(C=C1)C(=O)N(CCCN)C(C2=NC3=C(C=CC(=C3)Cl)C(=O)N2CC4=CC=CC=C4)C(C)C
保管

In vitro
Batch:

DMSO : 103 mg/mL ( (199.2 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 : 103 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

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)

mg/kg g μL

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。

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