[CAS NO. 1228591-30-7] TAK-632

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PRODUCTS SPECIFICATIONS [1228591-30-7]

Catalog

HY-15767

Brand

MCE

CAS

1228591-30-7

DESCRIPTION [1228591-30-7]

Overview

MDL	MFCD26960965
Molecular Weight	554.52
Molecular Formula	C27H18F4N4O3S
SMILES	O=C(NC1=CC(OC2=CC=C3N=C(NC(C4CC4)=O)SC3=C2C#N)=CC=C1F)CC5=CC=CC(C(F)(F)F)=C5

For research use only. We do not sell to patients.

3 Publications Citing Use of MCE

Summary

TAK-632 is a potent pan-RAF inhibitor with IC ₅₀ of 1.4, 2.4 and 8.3 nM for CRAF , BRAF ^V600E , BRAF ^WT , respectively.

IC50 & Target

IC50: 1.4 nM (C-RAF), 2.4 nM (BRAF ^V600E ), 8.3 nM (BRAF ^WT ),66 nM (Aurora B), 160 nM (VEGFR) ^[1]

In Vitro

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

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Appearance

Solid

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Solvent & Solubility

In Vitro:

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

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.8034 mL	9.0168 mL	18.0336 mL
5 mM	0.3607 mL	1.8034 mL	3.6067 mL
10 mM	0.1803 mL	0.9017 mL	1.8034 mL

* Please refer to the solubility information to select the appropriate solvent.

In Vivo:

1.

Add each solvent one by one: 10% DMSO >> 40% PEG300 >> 5% Tween-80 >> 45% saline

Solubility: 2.5 mg/mL (4.51 mM); Suspended solution; Need ultrasonic
2.

Add each solvent one by one: 10% DMSO >> 90% corn oil

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

* All of the co-solvents are available by MCE.