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TAK-632
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。
TAK-632图片
CAS NO:1228591-30-7
包装与价格:
包装价格(元)
10 mM * 1 mL in DMSO电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
200mg电议
500mg电议

产品介绍
TAK-632 是一种有效的pan-RAF抑制剂,作用于CRAFBRAFV600EBRAFWTIC50分别为 1.4,2.4 和 8.3 nM。
生物活性

TAK-632 is a potentpan-RAFinhibitor withIC50of 1.4, 2.4 and 8.3 nM forCRAF,BRAFV600E,BRAFWT, respectively.

IC50& Target[1]

c-Raf

1.4 nM (IC50)

Braf

8.3 nM (IC50)

Aurora B

66 nM (IC50)

PDGFRβ

120 nM (IC50)

PDGFRα

610 nM (IC50)

FGFR3

280 nM (IC50)

TIE2

740 nM (IC50)

IKKβ

3700 nM (IC50)

CDK1

790 nM (IC50)

CDK2

580 nM (IC50)

p38α

600 nM (IC50)

GSK3β

500 nM (IC50)

MEK1

3700 nM (IC50)

体外研究
(In Vitro)

TAK-632 inhibits PDGFRβ, FGFR3, GSK3β, CDK2, P38α, PDGFRα, TIE2, and CDK1 with a range of IC50values from 120-790 nM. CHK1, IKKβ, and MEK1 are inhibited over an IC50range of 1400-1700 nM. With 1 h of preincubation time, TAK-632 inhibits BRAF and CRAF in an ATP competitive manner (at low ATP concentrations BRAF IC50: 15 nM; CRAF: 8.1 nM). The respective biochemical activity of TAK-632 against BRAF and CRAF reduces to IC50values of 58 nM and 62 nM at high ATP concentrations.TAK-632 demonstrates strong inhibition of pMEK and pERK in HMVII cells with IC50values of 49 nM and 50 nM, respectively[1]. TAK-632 shows strong antiproliferative effects both in A375 and SK-MEL-2 cells (GI50of 40-190 nM in A375 cells and GI50of 190-250 nM in SK-MEL-2 cells)[2].

体内研究
(In Vivo)

TAK-632 demonstrates dramatically improved solubility (740 μg/mL) in pH 6.8 phosphate buffer and exhibits significant oral absorption (at a dose of 25 mg/kg, AUC, 32.47 μg h/mL; F, 51.7%) in rats. In a dog PK study, 10 mg/kg administration of TAK-632 also shows superior oral bioavailability (F: 108%).Oral single administration of TAK-632 inhibits pERK in tumors at 8 h after its administration over a dose range of 1.9-24.1 mg/kg. In particular, 9.7-24.1 mg/kg dosing with TAK-632 strongly inhibits pERK levels to 11% of the control. TAK-632 exhibits dose-dependent antitumor efficacy without severe body weight reduction over a dose range of 3.9-24.1 mg/kg. Significant tumor regression is observed at 9.7 mg/kg and 24.1 mg/kg (T/C=–2.1% and –12.1%, respectively)[1]. TAK-632 exhibits potent antitumor efficacy when orally administered at 60 mg/kg once daily (T/C=37%, P<0.001) or at 120 mg/kg once daily (T/C=29%, P<0.001) for 21 days without severe toxicity in NRAS-mutant melanoma using a SK-MEL-2 xenograft model[2].

分子量

554.52

性状

Solid

Formula

C27H18F4N4O3S

CAS 号

1228591-30-7

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 : 100 mg/mL(180.34 mM;Need ultrasonic)

配制储备液
浓度溶剂体积质量1 mg5 mg10 mg
1 mM1.8034 mL9.0168 mL18.0336 mL
5 mM0.3607 mL1.8034 mL3.6067 mL
10 mM0.1803 mL0.9017 mL1.8034 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 (4.51 mM); Suspended solution; Need ultrasonic

    此方案可获得 2.5 mg/mL (4.51 mM) 的均匀悬浊液,悬浊液可用于口服和腹腔注射。

    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%corn oil

    Solubility: ≥ 2.5 mg/mL (4.51 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (4.51 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。