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Dovitinib
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Dovitinib图片
CAS NO:405169-16-6
包装与价格:
包装价格(元)
10 mM * 1 mL in DMSO电议
5mg电议
10mg电议
50mg电议
100mg电议
200mg电议
500mg电议
1 g电议
5 g电议

产品名称
多韦替尼
CHIR-258
TKI258
产品介绍
Dovitinib (CHIR-258) 是口服有效的、多靶点的酪氨酸激酶 (RTK) 抑制剂,抑制FLT3c-KitCSF-1RFGFR1/FGFR3VEGFR1/VEGFR2/VEGFR3PDGFRα/PDGFRβIC50值分别为 1,2,36,8/9,10/13/8,27/210 nM。Dovitinib 具有抗肿瘤活性。
生物活性

Dovitinib (CHIR-258) is an orally active, potentmulti-targeted tyrosine kinase (RTK)inhibitor withIC50s of 1, 2, 36, 8/9, 10/13/8, 27/210 nM forFLT3,c-Kit,CSF-1R,FGFR1/FGFR3,VEGFR1/VEGFR2/VEGFR3andPDGFRα/PDGFRβ, respectively. Dovitinib has potent antitumor activity[1][2].

IC50& Target[1]

FLT3

1 nM (IC50)

c-Kit

2 nM (IC50)

FGFR1

8 nM (IC50)

FGFR3

9 nM (IC50)

VEGFR3

8 nM (IC50)

VEGFR1

10 nM (IC50)

VEGFR2

13 nM (IC50)

PDGFRβ

27 nM (IC50)

PDGFRα

210 nM (IC50)

CSF-1R

36 nM (IC50)

体外研究
(In Vitro)

Dovitinib (CHIR-258) shows more than 10-fold inhibition InsR (IC50=2 μM), EGFR1 (IC50=2 μM), c-Met (IC50>3 μM), EphrinA2 (EphA2; IC50=4 μM), Tie2 (IC50=4 μM), IGFR1 (IC50>10 μM), and HER2 (IC50>10 μM)[1].
Dovitinib (12.5-400 nM; 48 hours) potently inhibits the FGF-stimulated growth of WT and F384L-FGFR3-expressing B9 cells with IC50 values of 25 nM[1].
Dovitinib (100, 500 nM; 96 hours) inhibits FGF-mediated ERK1/2 phosphorylation and induces apoptosis of FGFR3-expressing human myeloma cell lines[1].
Dovitinib (72 hours) inhibits cell proliferation of KMS11 (FGFR3-Y373C), OPM2 (FGFR3-K650E), and KMS18 (FGFR3-G384D) cells with IC50 of values of 90 nM (KMS11 and OPM2) and 550 nM, respectively[1].
Dovitinib (100 nM) augments Dexamethasone (0.5 μM) cytotoxicity in KMS11 cells[1].
Dovitinib significantly reduces the basal phosphorylation levels of FGFR-1, FGFR substrate 2α (FRS2-α) and ERK1/2 but not Akt in both SK-HEP1 and 21-0208 cells[2].
Dovitinib enhances the BMP-2-induced alkaline phosphatase (ALP) induction, which is a representative marker of osteoblast differentiation. Dovitinib also stimulates the translocation of phosphorylated Smad1/5/8 into the nucleus and phosphorylation of mitogen-activated protein kinases, including ERK1/2 and p38[3].
Dovitinib strongly inhibits both the interaction of TNIK with ATP (Ki, 13 nM) and the activation of Wnt signaling effectors such as β-catenin and TCF4. Dovitinib also induces caspase-dependent apoptosis in IM-9 cells without significant cytotoxicity in PBMCs[4].

Cell Viability Assay[1]

Cell Line:WT and F384L-FGFR3-expressing B9 cells
Concentration:12.5, 25, 50, 100, 200, 300, 400 nM
Incubation Time:48 hours
Result:Potently inhibited the FGF-stimulated growth of the cells.

Apoptosis Analysis[1]

Cell Line:KMS11, OPM2, and KMS18 cells
Concentration:100 nM or 500 nM
Incubation Time:96 hours
Result:Induced apoptosis of FGFR3-expressing human myeloma cell lines.
体内研究
(In Vivo)

Dovitinib (CHIR-258; 10-60 mg/kg/day; gavage; for 21 days) has a significant antitumor effect[1].
Dovitinib (50 and 75 mg/kg) results in 97% and 98% tumor growth inhibition, respectively, and the maximal efficacy is at 50 mg/kg[2].

Animal Model:6- to 8-week-old female BNX mice with KMS11 cells[1]
Dosage:10, 30, 60 mg/kg
Administration:Gavage; daily for 21 days
Result:Had a significant antitumor effect in all 3 dose groups with 48%, 78.5%, and 94% growth inhibition in the 10 mg/kg, 30 mg/kg, and 60 mg/kg treatment.
Clinical Trial
分子量

392.43

性状

Solid

Formula

C21H21FN6O

CAS 号

405169-16-6

中文名称

多韦替尼;度维替尼

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder-20°C3 years
4°C2 years
In solvent-80°C6 months
-20°C1 month
溶解性数据
In Vitro: 

DMSO : 25 mg/mL(63.71 mM;Need ultrasonic and warming)

配制储备液
浓度溶剂体积质量1 mg5 mg10 mg
1 mM2.5482 mL12.7411 mL25.4823 mL
5 mM0.5096 mL2.5482 mL5.0965 mL
10 mM0.2548 mL1.2741 mL2.5482 mL
*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效
储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂:

——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂: 10% DMSO    40%PEG300   5%Tween-80   45% saline

    Solubility: ≥ 2.5 mg/mL (6.37 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (6.37 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH2O 中,得到澄清透明的生理盐水溶液
  • 2.

    请依序添加每种溶剂: 10% DMSO    90% (20%SBE-β-CDin saline)

    Solubility: ≥ 2.5 mg/mL (6.37 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (6.37 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中,再用生理盐水定容至 10 mL,完全溶解,澄清透明
  • 3.

    请依序添加每种溶剂: 10% DMSO    90%corn oil

    Solubility: ≥ 2.5 mg/mL (6.37 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (6.37 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

*以上所有助溶剂都可在本网站选购。