Ispinesib (SB-715992)

製品コードS1452 別名:CK0238273

Ispinesib (SB-715992)化学構造

分子量(MW):517.06

Ispinesib (SB-715992)は一種の有効で、特異性的で、可逆なKSP(kinesin spindle protein)阻害剤で、無細胞試験でKiapp値が1.7nMですが、CENP-E、RabK6、MCAK、MKLP1、KHCとKif1Aに抑制作用を表しません。臨床2期。

サイズ 価格(税別)  
JPY 69720.00
JPY 53120.00
JPY 161020.00

カスタマーフィードバック(4)

  • Representative photographs of fluorescent staining of microtubules and nuclei in MDA-MB-231 cells 24 h post-treatment with 4 nM of ispinesib or vinblastine or their combination. Arrows and arrowheads denote mitotic cells with monoploar and bipolar spindles, respectively. Scale bars, 20 um.

    Mol Oncol 2014 8(8), 1548-60. Ispinesib (SB-715992) purchased from Selleck.

    Original blot images and quantification of NKCC1 protein levels in the plasma membrane and cytosolic fractions of spinal cord slices with vehicle (Ctrl, 0.1% DMSO) or ispinesib (ISP, 1 uM). * p < 0.05; ** p < 0.01, compared with the vehicle control group. Error bars represent the S.E.

    J Biol Chem 2014 289(45), 31111-20. Ispinesib (SB-715992) purchased from Selleck.

  • KB-V1 cells were treated with BEZ235, BI 2536, IKK 16, ispinesib, and bryostatin-1 and then calcein AM (1 uM). Doses of each compound were generated from 1:2 dilutions of the highest concentration of 20 uM. The object intensities were plotted. Data presented are mean ± SD (n = 3).

    PLoS One 2013 8(4), e60334. Ispinesib (SB-715992) purchased from Selleck.

    Flow cytometry-based efflux assays were performed to examine KB-V1 cells incubated with either calcein AM (1 uM, red line) or calcein AM plus BEZ235, BI 2536, IKK 16, ispinesib, or bryostatin-1 (5 uM, blue line).

    PLoS One 2013 8(4), e60334. Ispinesib (SB-715992) purchased from Selleck.

製品安全説明書

Kinesin阻害剤の選択性比較

生物活性

製品説明 Ispinesib (SB-715992)は一種の有効で、特異性的で、可逆なKSP(kinesin spindle protein)阻害剤で、無細胞試験でKiapp値が1.7nMですが、CENP-E、RabK6、MCAK、MKLP1、KHCとKif1Aに抑制作用を表しません。臨床2期。
特性 An allosteric, potent, specific, and reversible inhibitor of the mitotic kinesin spindle protein (KSP) (HsEg5).
ターゲット
KSP (HsEg5) [1]
(Cell-free assay)
1.7 nM(Ki app)
体外試験

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]

細胞データ
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human HCT116 cells M1HNO2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NFnZOFA4OiCq M2LPd2dzd3e2aDDpcohq[mm2aX;uJI9nKGi3bXHuJGhEXDFzNjDj[YxteyCjZoTldkA4OiCqcoOgZpkhVVSVIHHzd4F6NCCLQ{WwQVEvOSCwTR?= M{XOPFI3Ozl4Nki4
human LNCAP cells Mon1S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M1u5VFczKGh? NVnKO4szT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hVE6FQWCgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KEGuYX3hdkBjdHWnIHHzd4F6NCCJSUWwQVAvODJ{IN88US=> NIrRUXYzOzN7NEG4NC=>
human hTERT-HME1 cells NXH4eJhjWHKxbHnm[ZJifGmxbjDhd5NigQ>? Mn3uO|IhcA>? NXS3elFuSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDoWGVTXC2KTVWxJINmdGy|IHHmeIVzKDd{IHjyd{BjgSCDbHHtZZIh[my3ZTDhd5NigSxiR1m1NF0xNjB|MjFOwG0> Mn\0NlIzPDh{NkK=
human PC3 cells NGPqTYpIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NH6xWpo4OiCq M{myWmdzd3e2aDDpcohq[mm2aX;uJI9nKGi3bXHuJHBEOyClZXzsd{Bi\nSncjC3NkBpenNiYomgRYxidWG{IHLseYUh[XO|YYmsJGdKPTB;MD6wOUDPxE1? NVPQcW1zOjN|OUSxPFA>
human K562 cells M1HNZXBzd2yrZnXyZZRqd25iYYPzZZk> M3j0cVczKGh? NU[wVVZZSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDLOVYzKGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDBcIFu[XJiYnz1[UBie3OjeTygS2k2OD1yLkC3NUDPxE1? NGHJUFczOjJ2OEK2Ni=>
human BxPC3 cells NHezSmJIem:5dHigbY5pcWKrdHnvckBie3OjeR?= NYfaOI1sPzJiaB?= Ml7TS5Jwf3SqIHnubIljcXSrb36gc4YhcHWvYX6gRphRSzNiY3XscJMh[W[2ZYKgO|IhcHK|IHL5JGFt[W2jcjDicJVmKGG|c3H5MEBIUTVyPUCuNFgh|ryP M1XFSFI{Ozl2MUiw
human BxPC3 cells M1mwXHBzd2yrZnXyZZRqd25iYYPzZZk> NU\FfZdRPzJiaB?= NX;HR4V2SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDCfHBEOyClZXzsd{Bi\nSncjC3NkBpenNiYomgRYxidWG{IHLseYUh[XO|YYmsJGdKPTB;MD6wPEDPxE1? NH60U5kzOjJ2OEK2Ni=>
human NCI-H1299 MXfHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NX:wS2ZQPzJiaB?= NXTZdmh4T3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hVkOLLVixNlk6KGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDBcIFu[XJiYnz1[UBie3OjeTygS2k2OD1yLkC4NkDPxE1? M1fEe|I{Ozl2MUiw
human NCI-H1299 cells MUDQdo9tcW[ncnH0bY9vKGG|c3H5 Ml\MO|IhcA>? NHraNI5CdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF7DTU1JOTJ7OTDj[YxteyCjZoTldkA4OiCqcoOgZpkhSWyjbXHyJIJtfWViYYPzZZktKEeLNUC9NE4xQDJizszN MXuyNlI1QDJ4Mh?=
human HeLa cells NV;wN4M6WHKxbHnm[ZJifGmxbjDhd5NigQ>? NWXKXoIzPDhiaB?= M1zhWWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSHXMZUBk\WyuczDh[pRmeiB2ODDodpMh[nliTWTUJIF{e2G7LDDJR|UxRTFizszN NEPzSpkzPDF6NEe3Oi=>
MCF7 cells M3LFTnBzd2yrZnXyZZRqd25iYYPzZZk> NES2[JU1QCCq NHvrfoxCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3DSlch[2WubIOgZYZ1\XJiNEigbJJ{KGK7IF3UWEBie3OjeTygTWM2OD1zLkOg{txO Mo\oNlQyQDR5N{[=

多くの細胞株試験データを見る場合、クリックしてください

体内試験 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]

お薦めの試験操作(参考用のみ)

キナーゼ試験:[1]
+ 展開

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.
細胞試験: [4]
+ 展開
  • 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.
    (参考用のみ)
動物試験:[4]
+ 展開
  • 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;
  • 製剤: Dissolved in 10% ethanol, 10% cremophor, and 80% D5W (dextrose 5%)
  • 投薬量: 10 mg/kg for nude mice or 8 mg/kg for SCID mice
  • 投与方法: Intraperitoneal injection on a q4d× schedule (3 doses, every 4 day
    (参考用のみ)

溶解度 (25°C)

体外 DMSO 103 mg/mL (199.2 mM)
Ethanol 103 mg/mL (199.2 mM)
Water Insoluble

* 溶解度検測はSelleck技術部門によって行いますので、文献より提供された溶解度と差異がある可能性がありますが、生産工芸と不同ロット(lot)で起きる正常な現象ですから、ご安心ください。

化学情報

分子量 517.06
化学式

C30H33ClN4O2

CAS No. 336113-53-2
保管
別名 CK0238273

便利ツール

モル濃度計算器

モル濃度計算器

解決のために必要とされるマス、ボリュームまたは濃度を計算してください。

マス (g) = 濃度 (mol/L) x ボリューム (L) x 分子量 (g/mol)

モル濃度計算器方程式

  • マス
    濃度
    ボリューム
    分子量

*貯蔵液を準備するとき、常に、オンであるとわかる製品のバッチに特有の分子量を使って、を通してラベルとMSDS/COA(製品ページで利用可能な)。

希釈計算器

希釈計算器

貯蔵液を準備することを要求される希釈剤を計算してください. セレック希釈計算器は、以下の方程式に基づきます:

開始濃度 x 開始体積 = 最終濃度 x 最終体積

希釈の計算式

この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 輸入 輸出 )

  • C1
    V1
    C2
    V2

常に貯蔵液を準備するとき、小びんラベルとMSDS/COA(オンラインで利用できる)で見つかる製品のバッチに特有の分子量を使ってください。

連続希釈計算器方程式

  • 連続希釈剤

  • 計算結果

  • 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):
分子量計算器

分子量计算器

そのモル質量と元素組成を計算するために、合成物の化学式を入力してください:

総分子量:g/mol

チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2

モル濃度計算器

マス 濃度 ボリューム 分子量

臨床試験

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00607841 Completed Breast Neoplasms Cytokinetics December 2007 Phase 1|Phase 2
NCT00363272 Completed Childhood Burkitt Lymphoma|Childhood Central Nervous System Germ Cell Tumor|Childhood Choroid Plexus Tumor|Childhood Craniopharyngioma|Childhood Grade I Meningioma|Childhood Grade II Meningioma|Childhood Grade III Meningioma|Childhood High-grade Cerebral Astrocytoma|Childhood Infratentorial Ependymoma|Childhood Low-grade Cerebral Astrocytoma|Childhood Spinal Cord Neoplasm|Childhood Supratentorial Ependymoma|Recurrent Childhood Brain Stem Glioma|Recurrent Childhood Brain Tumor|Recurrent Childhood Cerebellar Astrocytoma|Recurrent Childhood Cerebral Astrocytoma|Recurrent Childhood Ependymoma|Recurrent Childhood Grade III Lymphomatoid Granulomatosis|Recurrent Childhood Large Cell Lymphoma|Recurrent Childhood Lymphoblastic Lymphoma|Recurrent Childhood Medulloblastoma|Recurrent Childhood Small Noncleaved Cell Lymphoma|Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor|Recurrent Childhood Visual Pathway and Hypothalamic Glioma|Unspecified Childhood Solid Tumor, Protocol Specific National Cancer Institute (NCI) June 2006 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
NCT00096499 Completed Adenocarcinoma of the Prostate|Recurrent Prostate Cancer|Stage IV Prostate Cancer National Cancer Institute (NCI) April 2005 Phase 2
NCT00095628 Completed Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma|Recurrent Metastatic Squamous Neck Cancer With Occult Primary|Recurrent Salivary Gland Cancer|Recurrent Squamous Cell Carcinoma of the Hypopharynx|Recurrent Squamous Cell Carcinoma of the Larynx|Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity|Recurrent Squamous Cell Carcinoma of the Oropharynx|Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity|Recurrent Verrucous Carcinoma of the Larynx|Recurrent Verrucous Carcinoma of the Oral Cavity|Stage IV Squamous Cell Carcinoma of the Hypopharynx|Stage IV Squamous Cell Carcinoma of the Larynx|Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity|Stage IV Squamous Cell Carcinoma of the Oropharynx|Stage IV Verrucous Carcinoma of the Larynx|Stage IV Verrucous Carcinoma of the Oral Cavity|Stage IVA Salivary Gland Cancer|Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity|Stage IVB Salivary Gland Cancer|Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity|Stage IVC Salivary Gland Cancer|Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity National Cancer Institute (NCI) January 2005 Phase 2
NCT00103311 Completed Recurrent Colon Cancer|Recurrent Rectal Cancer|Stage IIIA Colon Cancer|Stage IIIA Rectal Cancer|Stage IIIB Colon Cancer|Stage IIIB Rectal Cancer|Stage IIIC Colon Cancer|Stage IIIC Rectal Cancer|Stage IVA Colon Cancer|Stage IVA Rectal Cancer|Stage IVB Colon Cancer|Stage IVB Rectal Cancer National Cancer Institute (NCI) January 2005 Phase 2

技術サポート

ストックの作り方、阻害剤の保管する方法、細胞実験や動物実験に注意すべきな点を全部含めており、製品を取扱う時よくあった質問に対して取扱説明書でお答えいたします。

Handling Instructions

他の質問がある場合は、お気軽くお問合せください。

  • * 必須

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細胞株 試験類型 濃度 培養時間 溶剤類型 活性叙述 PMID