Dovitinib (TKI258) Lactate

目录号:S7765 别名: CHIR258

Dovitinib (TKI258) Lactate Chemical Structure

Molecular Weight(MW): 482.51

Dovitinib (TKI258) Lactate是Dovitinib的乳酸盐,Dovitinib是一种多靶点的PTK抑制剂,主要对第III类(FLT3/c-Kit)发挥作用,IC50为1 nM/2 nM,对第IV 类(FGFR1/3)和第V 类(VEGFR1-4) RTKs也有效,IC50为8-13 nM,对InsR,EGFR,c-Met,EphA2,Tie2,IGFR1 和HER2作用较差。Phase 4。

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客户使用Selleck该产品发表文献10篇:

客户使用该产品的5个实验数据:

  • (c) Percent survival for the AGS cancer cell line is shown with FGFR2 inhibitors of varying specificity. (d) The KatoIII diffuse gastric cancer cell line was treated with FGFR2 inhibitors of varying specificity. The Y-axis depicts percent survival versus the X-axis with log concentrations. In all panels, error bars represent standard error of the mean. The difference in percent cell survival between KatoIII and AGS cells was statistically significant (P <0.05) at the three highest concentrations of all drugs, except Brivanib which was only significant at the highest concentration.

    Genome Biol, 2014, 15(8):428.. Dovitinib (TKI258) Lactate purchased from Selleck.

    Stable BaF3.FGFR2 cells were pretreated in IL-3-free BaF3 media for 90 minutes at 37°C. After the 90-minute incubation period, the media were removed and the cells were incubated for 7.5 minutes at 37°C with media containing 5 µg/ml heparan sulfate and 16 nM FGF10. Cells were lysed in lysis buffer containing phosphatase inhibitors and 150 µg of total protein was separated on an SDS-PAGE, transferred to a nitrocellulose membrane, and probed using an anti-pan-phospho-FGFR, anti-FGFR2 (BEK-C17), and anti-tubulin antibodies.

    Neoplasia, 2013, 15(8):975-88. Dovitinib (TKI258) Lactate purchased from Selleck.

  • The small molecule kinase inhibitor dovitinib can partially reverse the effects of FGF-2. Quantification of centrosome aberrations (A), mitotic defects (B), deviations from the modal number of chromosome 8 (C) and Comet assay features of DNA damage (D–F). LNCaP cells were treated with dH2O (control for rFGF-2), 10 ng/ml rFGF-2, 0.1% DMSO (control for dovitinib), 1μM dovitinib or both rFGF-2 and dovitinib for 72 hour. Note that dovitinib could partially reverse the effects of rFGF-2 on the observed cellular alterations. Mean and standard error of at least 3 independent experiments are shown. Asterisks indicate the statistical significance level as indicated above with cells treated with FGF-2 alone used as reference.

    Urol Oncol, 2018, 36(8):365. Dovitinib (TKI258) Lactate purchased from Selleck.

    The effect of dovitinib on BMP-2-induced osteoblast differentiation was detected by visualizing the induction of ALP in C2C12 cells. Scale bars represent 100 μm.

    Mol Cells, 2016, 39(5):389-94. Dovitinib (TKI258) Lactate purchased from Selleck.

  • IM-9 cells were treated with 0, 1, or 3 μM dovitinib for 24 h. After protein concentration determination, the expression levels in the cytosolic (C) and nuclear (N) fractions were measured by western blot analysis. Actin and histone H3 were used as loading controls.

    Amino Acids, 2016, 48(7):1591-9. Dovitinib (TKI258) Lactate purchased from Selleck.

产品安全说明书

FLT3抑制剂选择性比较

生物活性

产品描述 Dovitinib (TKI258) Lactate是Dovitinib的乳酸盐,Dovitinib是一种多靶点的PTK抑制剂,主要对第III类(FLT3/c-Kit)发挥作用,IC50为1 nM/2 nM,对第IV 类(FGFR1/3)和第V 类(VEGFR1-4) RTKs也有效,IC50为8-13 nM,对InsR,EGFR,c-Met,EphA2,Tie2,IGFR1 和HER2作用较差。Phase 4。
靶点
FLT3 [1]
()
c-Kit [1] FGFR1 [1] VEGFR3/FLT4 [1] FGFR3 [1]
1 nM 2 nM 8 nM 8 nM 9 nM
体外研究

Dovitinib有效抑制FGF刺激的表达WT和F384L-FGFR3的B9细胞生长,IC50 为25 nM。此外,Dovitinib抑制表达各种活化的FGFR3突变体的B9细胞的增殖。有趣的是,观察到不同 FGFR3突变体对Dovitinib敏感性差别非常小,对每个不同突变体的IC50 范围为70 到90 nM。包含载体的IL-6依赖性B9细胞,仅B9-MINV对高达1 μM浓度的Dovitinib的抑制活性耐受。Dovitinib抑制KMS11 (FGFR3-Y373C),OPM2 (FGFR3-K650E),和KMS18 (FGFR3-G384D)细胞的增殖,IC50分别为90 nM (KMS11 和 OPM2)和550 nM。在表达FGFR3的原始MM细胞中,Dovitinib抑制FGF介导的ERK1/2磷酸化,并诱导细胞毒性。用500 nM Dovitinib处理的细胞,与具有一定程度耐受性的BMSCs一起培养,细胞表现出44.6%的生长抑制,相比于不含BMSCs 的培养基,细胞出现71.6%的生长抑制。Dovitinib抑制M-NFS-60,一种M-CSF生长驱动的小鼠成髓细胞系的增殖,半数有效浓度(EC50) 为220 nM。[1] SK-HEP1细胞用Dovitinib处理导致细胞数量剂量依赖性减少,并且G2/M期阻滞,G0/G1和S期减少,贴壁非依赖性生长抑制以及bFGF诱导的细胞运动阻断。Dovitinib在SK-HEP1细胞中的IC50大约为1.7 μM。在SK-HEP1 和 21-0208 细胞中,Dovitinib也会显著减少FGFR-1,FGFR底物2α (FRS2-α) 和ERK1/2的基础磷酸化水平,而不影响Akt。在21-0208 HCC细胞中,Dovitinib显著抑制bFGF诱导的FGFR-1,FRS2-α,ERK1/2磷酸化,而不影响Akt。[2]

体内研究 Dovitinib在体内诱导细胞抑制和细胞毒性应答,导致表达FGFR3的肿瘤细胞消退。[1] Dovitinib对表达靶受体酪氨酸激酶(RTKs)的肿瘤异种移植物表现出剂量和暴露依赖性抑制作用。Dovitinib有效抑制六个HCC系的肿瘤生长。血管生成的抑制与FGFR/PDGFRβ/VEGFR2信号通路的失活相关。在原位接种模型中,Dovitinib有效抑制原发肿瘤生长和肺转移,并显著延长小鼠生存时间。[2] Dovitinib给药导致显著的肿瘤生长抑制和肿瘤消退,包括多数已生成的肿瘤(500-1,000mm3)。[3]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验:[1]
- 合并

体外激酶试验:

Dovitinib对RTKs抑制的50%抑制浓度(IC50)值在时间分辨荧光(TRF)或放射性形式中测定,测量Dovitinib对磷酸盐被各自的酶转移到底物中的抑制。FGFR3,FGFR1,PDGFRβ,和VEGFR1-3的激酶域在50 mM HEPES (N-2-羟乙基哌嗪乙烷磺酸-N-2-乙磺酸),pH 7.0,2 mM MgCl2,10 mM MnCl2,1 mM NaF,1 mM 二硫苏糖醇(DTT),1 mg/mL 牛血清白蛋白(BSA),0.25 μM生物素化的多肽底物(GGGGQDGKDYIVLPI),和1到30 μM 三磷酸腺苷(ATP) (取决于对各自酶的Km)中测定。ATP浓度达到或略低于Km。对于c-KIT和FLT3反应,pH提高为7.5,ATP为0.2到8 μM,并含有0.25 到1 μM的 生物素化底物肽(GGLFDDPSYVNVQNL)。反应在室温下培养1到4小时,磷酸化的多肽在包含停止反应缓冲液(25 mM EDTA [乙二胺四乙酸],50 mM HEPES,pH 7.5)的链霉亲和素涂覆的微量滴定板中捕获。磷酸化的底物肽用DELFIA TRF系统使用铕标记的抗磷酸酪氨酸抗体PT66测量。Dovitinib的IC50浓度使用非线性回归与4.1版XL-Fit数据分析软件(IDBS)计算。集落刺激因子-1受体(CSF-1R),PDGFRα,胰岛素受体(InsR),和胰岛素样生长因子受体1 (IGFR1)在ATP浓度接近Km下测定。
细胞实验:[1]
- 合并
  • Cell lines: B9细胞,MM细胞系
  • Concentrations: 100 nM
  • Incubation Time: 48-96 小时
  • Method: 细胞活性通过3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium (MTT)染料吸光度评估。细胞以5×103 (B9 细胞)或2×104 (MM 细胞系)细胞每孔的密度接种于96孔板。细胞与指示的30 ng/mL aFGF 和100 μg/mL肝素或1% IL-6以及逐渐增加浓度的Dovitinib进行培养。对每种浓度的Dovitinib,10 μL等份的药物或DMSO在培养基中稀释后加入。对于联合用药研究,细胞与指示的0.5 μM dexamethasone,100 nM Dovitinib,或两者同时进行培养。为评估Dovitinib对附着于BMSCs的MM细胞生长的作用,104 KMS11细胞在BMSC涂覆的96孔板中,Dovitinib存在或不存在下进行培养。板培养48到96小时。对于巨噬细胞集落刺激因子(M-CSF)介导的生长的评估,5×103 M-NFS-60细胞/孔与连续稀释的Dovitinib和10 ng/mL M-CSF,在粒细胞-巨噬细胞集落刺激因子(GM-CSF)不存在下进行培养。72小时后,细胞活性使用Cell Titer-Glo试验测定。每种实验条件以一式三份进行。
    (Only for Reference)
动物实验:[1]
- 合并
  • Animal Models: 负荷KMS11细胞的8周大雌性BNX小鼠
  • Formulation: 5 mM柠檬酸盐缓冲液
  • Dosages: 10,30,或60 mg/kg
  • Administration: p.o.
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 100 mg/mL (207.24 mM)
Water 66 mg/mL warmed (136.78 mM)
Ethanol 1 mg/mL warmed (2.07 mM)

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 482.51
化学式

C24H27FN6O4

CAS号 915769-50-5
储存条件 粉状
溶于溶剂
别名 CHIR258

计算器

摩尔浓度计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系,公式为:

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量

*在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

用本工具协助配置特定浓度的溶液,使用的计算公式为:

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )

  • C1
    V1
    C2
    V2

在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • 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):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

注:化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02268435 Withdrawn Drug: dovitinib plus imatinib Gastrointestinal Stromal Tumors Asan Medical Center March 2015 Phase 1
NCT01700270 Completed Drug: dovitinib (TKI258)|Drug: fluvoxamine Advanced Solid Tumors Excluding Breast Cancer Novartis Pharmaceuticals|Novartis May 2013 Phase 1
NCT01680796 Withdrawn Drug: Dovitinib|Drug: Bortezomib|Drug: Dexamethasone Multiple Myeloma University of Florida|Novartis Pharmaceuticals February 2013 Phase 1
NCT01266070 Terminated Drug: Dovitinib Von Hippel-Lindau Syndrome M.D. Anderson Cancer Center|Novartis November 2012 Phase 2
NCT01515969 Terminated Drug: Erlotinib hydrochloride|Drug: Dovitinib lactate Non-small Cell Lung Cancer (NSCLC) Recurrent|Non-small Cell Lung Cancer (NSCLC) Stage IV Heather Wakelee|Genentech Inc.|Novartis|Stanford University July 2012 Phase 1

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID