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Rebastinib
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。
Rebastinib图片
CAS NO:1020172-07-9
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

产品名称
DCC-2036
产品介绍
Rebastinib (DCC-2036) 是一种口服有效的,非 ATP 竞争性的Bcr-Abl抑制剂,作用于Abl1WTAbl1T315IIC50分别为 0.8 nM 和 4 nM,也抑制 SRC,KDR,FLT3 和 Tie-2,低活性作用于c-Kit。
生物活性

Rebastinib (DCC-2036) is an orally active, non-ATP-competitive Bcr-Ablinhibitor forAbl1WTandAbl1T315IwithIC50s of 0.8 nM and 4 nM, respectively. Rebastinib also inhibitsSRC, KDR,FLT3, andTie-2, and has low activity to seen towardsc-Kit.

IC50& Target

IC50: 0.75±0.11 nM (ABL1WT), 2±0.3 nM (FLT3), 4±0.3 nM (KDR), 6±0.3 nM (TIE2), 34±6 nM (SRC)[1]

体外研究
(In Vitro)

Rebastinib potently (IC500.82 nM) inhibits u-ABL1native, which is thought to exist predominantly in the inactive type II conformation. In addition, Rebastinib also strongly inhibits p-ABL1native(IC502 nM), which more readily adopts an active, Type I conformation[1].
Rebastinib potently inhibits both u-ABL1T315I(IC505 nM) and p-ABL1T315I(IC504 nM), both of which exist predominately in the Type I conformation due to stabilization of an activating hydrophobic spine by the T315I mutation[1].
In addition to ABL1, Rebastinib also inhibits the SRC family kinases LYN, SRC, FGR, and HCK, and PDGFRα, and PDGFRβ with IC50of 29±1, 34±6, 38±1, 40±1, 70±10 and 113±10 nM, respectively. Notably, Rebastinib spared c-KIT (IC50481 nM)[1].
Rebastinib effectively inhibits the proliferation of Ba/F3 cells expressing native BCR-ABL1native(IC505.4 nM). Rebastinib also inhibits proliferation of the Ph+cell line K562 (IC505.5 nM)[1].
Rebastinib also inhibits proliferation of several common TKI-resistant mutants of BCR-ABL1, including G250E, Q252H, Y235F, E255K, V299L, F317L, and M351T, at IC50s ranging from 6-150 nM. Rebastinib effectively inhibits autophosphorylation of BCR-ABL1native(IC5029 nM) and BCR-ABL1T315I(IC5018 nM), as well as the phosphorylation of STAT5 in both cell lines (IC5028 nM and 13 nM, respectively)[1].

体内研究
(In Vivo)

A single dose of Rebastinib (DCC-2036; oral; 100 mg/kg) affords circulating plasma levels that exceeds 12 μM for up to 24 hours, and effectively inhibits BCR-ABL1 signaling for up to 8 hours in Ba/F3-BCR-ABL1T315Ileukemia cells isolated from BM and spleen of tumor-bearing mice[1].
Treatment of mice bearing Ba/F3-BCR-ABL1T315Ileukemia cells with Rebastinib at 100 mg/kg once daily by oral gavage significantly prolonged their survival, while STI571 at 100 mg/kg twice daily is ineffective[1].
In this aggressive allograft model, Rebastinib is as effective for treatment of BCR-ABLT315Ileukemia as STI571 at 100 mg/kg twice daily in BCR-ABL1nativeleukemia, and reduces the leukemia cell burden in the spleens of treated mice[1].

Clinical Trial
分子量

553.59

性状

Solid

Formula

C30H28FN7O3

CAS 号

1020172-07-9

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 : 50 mg/mL(90.32 mM;ultrasonic and warming and heat to 80℃)

配制储备液
浓度溶剂体积质量1 mg5 mg10 mg
1 mM1.8064 mL9.0320 mL18.0639 mL
5 mM0.3613 mL1.8064 mL3.6128 mL
10 mM0.1806 mL0.9032 mL1.8064 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: ≥ 2.08 mg/mL (3.76 mM); Clear solution

    此方案可获得 ≥ 2.08 mg/mL (3.76 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 20.8 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: ≥ 2.08 mg/mL (3.76 mM); Clear solution

    此方案可获得 ≥ 2.08 mg/mL (3.76 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 20.8 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
*以上所有助溶剂都可在本网站选购。