TAK-632

Name: TAK-632
Brand: MedChemExpress
SKU: HY-15767
Rating: 5.0 (7 reviews)

Cat. No.: HY-15767 Purity: 98.84%: FAQs
Data Sheet SDS COA Handling Instructions

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TAK-632 is a potent pan-RAF inhibitor with IC₅₀ of 1.4, 2.4 and 8.3 nM for CRAF, BRAF^V600E, BRAF^WT, respectively.

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

TAK-632 Chemical Structure

CAS No. : 1228591-30-7

Size	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	In-stock	Estimated Time of Arrival: December 31
10 mg	In-stock	Estimated Time of Arrival: December 31
25 mg	In-stock	Estimated Time of Arrival: December 31
50 mg	In-stock	Estimated Time of Arrival: December 31
100 mg	In-stock	Estimated Time of Arrival: December 31
200 mg	Get quote
500 mg	Get quote

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Customer Review

Based on 7 publication(s) in Google Scholar

4 Publications Citing Use of MCE TAK-632

: TAK-632 purchased from MedChemExpress. Usage Cited in: Br J Pharmacol. 2019 Jun;176(12):2095-2108. [Abstract]; HEK293T cells are transfected with FLAG-RIPK1 or RIPK3-V5. After 12 h, the cells are treated with TAK-632 as the indicated concentrations for 6 h. Cell lysates are then analyzed by SDS-PAGE and immunoblotted with the indicated antibodies. All western data are representative of five independent experiments.

: TAK-632 purchased from MedChemExpress. Usage Cited in: Br J Pharmacol. 2019 Jun;176(12):2095-2108. [Abstract]; L929 cells are pretreated with TAK-632 (5 μM) followed by stimulated with mTNF-α (20 ng) plus z-VAD-FMK (20 μM) (TZ) at the indicated time points. Cells are lysed and immunoblotted with the indicated antibodies.

: TAK-632 purchased from MedChemExpress. Usage Cited in: Br J Pharmacol. 2019 Jun;176(12):2095-2108. [Abstract]; HT-29 cells are pretreated with TAK-632 (10 μM) followed by stimulation with TSZ at the indicated time points. Cells are lysed and immunoblotted with the indicated antibodies.

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Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

TAK-632 is a potent pan-RAF inhibitor with IC₅₀ 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]

Cellular Effect

Cell Line	Type	Value	Description	References
A-375	IC₅₀	12 nM Compound: 8B, TAK-632	Inhibition of BRAF V600E mutant in human A375 cells assessed as phosphorylation of MEK after 2 hrs by Western blotting analysis Inhibition of BRAF V600E mutant in human A375 cells assessed as phosphorylation of MEK after 2 hrs by Western blotting analysis	[PMID: 23906342]
A-375	IC₅₀	16 nM Compound: 8B, TAK-632	Inhibition of BRAF V600E mutant in human A375 cells assessed as phosphorylation of ERK after 2 hrs by Western blotting analysis Inhibition of BRAF V600E mutant in human A375 cells assessed as phosphorylation of ERK after 2 hrs by Western blotting analysis	[PMID: 23906342]
A-375	IC₅₀	160 nM Compound: 127; TAK-632	Antiproliferative activity against human A-375 cells harbouring B-Raf V600E mutant by SRB assay Antiproliferative activity against human A-375 cells harbouring B-Raf V600E mutant by SRB assay	[PMID: 32798788]
A-375	GI₅₀	66 nM Compound: 8B, TAK-632	Antiproliferative activity against human A375 cells assessed as growth inhibition after 72 hrs by chemi-luminescence cell viability assay Antiproliferative activity against human A375 cells assessed as growth inhibition after 72 hrs by chemi-luminescence cell viability assay	[PMID: 23906342]
A549	IC₅₀	8.5 μM Compound: TAK-632	Cytotoxicity against human A549 cells assessed as cell growth inhibition after 72 hrs by MTS assay Cytotoxicity against human A549 cells assessed as cell growth inhibition after 72 hrs by MTS assay	[PMID: 26745854]
CHL-1	IC₅₀	2.07 nM Compound: 127; TAK-632	Antiproliferative activity against human CHL-1 cells harbouring wild type B-Raf by SRB assay Antiproliferative activity against human CHL-1 cells harbouring wild type B-Raf by SRB assay	[PMID: 32798788]
COLO 205	IC₅₀	0.025 μM Compound: 3; TAK-632	Cytotoxicity against human COLO205 cells harboring B-Raf V600E mutant assessed as growth inhibition after 72 hrs by MTT assay Cytotoxicity against human COLO205 cells harboring B-Raf V600E mutant assessed as growth inhibition after 72 hrs by MTT assay	[PMID: 27155899]
HCT-116	IC₅₀	0.362 μM Compound: 3; TAK-632	Cytotoxicity against human HCT116 cells harboring wild type B-Raf assessed as growth inhibition after 72 hrs by MTT assay Cytotoxicity against human HCT116 cells harboring wild type B-Raf assessed as growth inhibition after 72 hrs by MTT assay	[PMID: 27155899]
HMCB cell line	IC₅₀	350 nM Compound: 127; TAK-632	Antiproliferative activity against human HMCB cells harbouring wild type B-Raf by SRB assay Antiproliferative activity against human HMCB cells harbouring wild type B-Raf by SRB assay	[PMID: 32798788]
HMV-2 cell line	IC₅₀	200 nM Compound: 127; TAK-632	Antiproliferative activity against human HMV-2 cells harbouring B-Raf G469V mutant by SRB assay Antiproliferative activity against human HMV-2 cells harbouring B-Raf G469V mutant by SRB assay	[PMID: 32798788]
HMV-2 cell line	GI₅₀	200 nM Compound: 8B, TAK-632	Antiproliferative activity against human HMVII cells assessed as growth inhibition after 72 hrs by chemi-luminescence cell viability assay Antiproliferative activity against human HMVII cells assessed as growth inhibition after 72 hrs by chemi-luminescence cell viability assay	[PMID: 23906342]
HT-144	IC₅₀	110 nM Compound: 127; TAK-632	Antiproliferative activity against human HT-144 cells harbouring B-Raf V600E mutant by SRB assay Antiproliferative activity against human HT-144 cells harbouring B-Raf V600E mutant by SRB assay	[PMID: 32798788]
HT-29	CC₅₀	> 50 μM Compound: 6; TAK-632	Cytotoxicity against human HT-29 cells measured after 12 hrs by CellTiter-Glo Luminescent assay Cytotoxicity against human HT-29 cells measured after 12 hrs by CellTiter-Glo Luminescent assay	[PMID: 31095385]
HT-29	IC₅₀	0.033 μM Compound: 3; TAK-632	Cytotoxicity against human HT-29 cells harboring B-Raf V600E mutant assessed as growth inhibition after 72 hrs by MTT assay Cytotoxicity against human HT-29 cells harboring B-Raf V600E mutant assessed as growth inhibition after 72 hrs by MTT assay	[PMID: 27155899]
HT-29	EC₅₀	1.44 μM Compound: 6; TAK-632	Anti-necroptotic activity in human HT-29 cells assessed as inhibition of NFalpha/SM-164/Z-VAD-fmk-induced necroptosis measured after 12 hrs by celltiter-glo luminescent cell viability assay Anti-necroptotic activity in human HT-29 cells assessed as inhibition of NFalpha/SM-164/Z-VAD-fmk-induced necroptosis measured after 12 hrs by celltiter-glo luminescent cell viability assay	[PMID: 31095385]
HT-29	EC₅₀	1.44 μM Compound: TAK-632; 75	Anti-necrotic activity in TSZ induced human HT-29 cells incubated for 16 hrs in presence of TSZ by flow cytometry analysis Anti-necrotic activity in TSZ induced human HT-29 cells incubated for 16 hrs in presence of TSZ by flow cytometry analysis	[PMID: 36346971]
HT-29	EC₅₀	1440 nM Compound: TAK-632	Anti-necroptotic activity in human HT-29 cells assessed as inhibition of TNFalpha/Z-VAD-fmk (TCZ)-induced necroptosis pretreated for 8 to 12 hrs Anti-necroptotic activity in human HT-29 cells assessed as inhibition of TNFalpha/Z-VAD-fmk (TCZ)-induced necroptosis pretreated for 8 to 12 hrs	[PMID: 33964444]
Malme-3M	IC₅₀	50 nM Compound: 127; TAK-632	Antiproliferative activity against human Malme-3M cells harbouring B-Raf V600E mutant by SRB assay Antiproliferative activity against human Malme-3M cells harbouring B-Raf V600E mutant by SRB assay	[PMID: 32798788]
SK-MEL-2	IC₅₀	60 nM Compound: 127; TAK-632	Antiproliferative activity against human SK-MEL-2 cells harbouring wild type B-Raf by SRB assay Antiproliferative activity against human SK-MEL-2 cells harbouring wild type B-Raf by SRB assay	[PMID: 32798788]

In Vitro

TAK-632 inhibits PDGFRβ, FGFR3, GSK3β, CDK2, P38α, PDGFRα, TIE2, and CDK1 with a range of IC₅₀ values from 120-790 nM. CHK1, IKKβ, and MEK1 are inhibited over an IC₅₀ 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 IC₅₀: 15 nM; CRAF: 8.1 nM). The respective biochemical activity of TAK-632 against BRAF and CRAF reduces to IC₅₀ values of 58 nM and 62 nM at high ATP concentrations.TAK-632 demonstrates strong inhibition of pMEK and pERK in HMVII cells with IC₅₀ values of 49 nM and 50 nM, respectively^[1]. TAK-632 shows strong antiproliferative effects both in A375 and SK-MEL-2 cells (GI₅₀ of 40-190 nM in A375 cells and GI₅₀ of 190-250 nM in SK-MEL-2 cells)^[2].

MedChemExpress (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].

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

Molecular Weight

554.52

Formula

C₂₇H₁₈F₄N₄O₃S

CAS No.

1228591-30-7

Appearance

Solid

Color

White to off-white

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

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL (180.34 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

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

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 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

This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (4.51 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

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Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 98.84%

Select Batch:

Data Sheet (278 KB) SDS (392 KB)

COA (245 KB) LCMS (97 KB)

Handling Instructions (2659 KB)

References

[1]. Okaniwa M, et al. Discovery of a selective kinase inhibitor (TAK-632) targeting pan-RAF inhibition: design, synthesis, and biological evaluation of C-7-substituted 1,3-benzothiazole derivatives. J Med Chem. 2013 Aug 22;56(16):6478-94. [Content Brief]

[2]. Nakamura A, et al. Antitumor activity of the selective pan-RAF inhibitor TAK-632 in BRAF inhibitor-resistant melanoma. Cancer Res. 2013 Oct 11. [Content Brief]

Kinase Assay ^[2]	Immunoprecipitated BRAF or CRAF is incubated with recombinant inactive MEK (K97R) at 30°C for 30 minutes in kinase reaction buffer containing ATP/Mg²⁺. RAS/RAF wild-type (A431, CsFb, and HeLa), KRAS-mutant (A549, HCT-116, and MIA PaCa-2), and NRAS-mutant melanoma (GAK, HMV-II, and SK-MEL-2) cells are treated with TAK-632 (0, 0.32, 1.6, 8, 40, 200, 1000 and 5000 nM) at the indicated concentrations for 2 hours. Cell lysates are analyzed by Western blot analysis^[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay ^[2]	Cell viability is assessed (3 replicates) using the Sulforhodamine B assay or by the CellTiter-Glo luminescent cell viability assay. The concentrations of TAK-632 that produced 50% growth inhibition (GI₅₀) are calculated using PCP software. The combination index (CI) is calculated using CalcuSyn software. To investigate the antiproliferative activity of TAK-632, we performed proliferation assays in various cell lines harboring mutated BRAF, NRAS, or KRAS. HMV-II, SK-MEL-2, or A375 cells are cotreated with TAK-632 and TAK-733 at the indicated concentrations for 72 hours. Cell viability is measured. The CI value at EC₅₀ is calculated. A375 cells stably expressing NRAS^Q61K or ΔN-BRAF are cotreated with TAK-632 and TAK-733 at the indicated concentrations for 72 hours. Cell viability is measured. The CI value at EC₅₀ is calculated^[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[2]	Mice^[2] The xenograft-implanted nude mice are used. Mice bearing SK-MEL-2 xenografts are treated once daily for 21 consecutive days with vehicle or TAK-632 at the indicated concentrations (10 mice per each treatment group). Day 0 indicates the beginning of treatment. Tumors are measured twice a week. Mice bearing SK-MEL-2 xenografts are treated once daily (QD) for 3 days with vehicle, TAK-632 at 60 mg/kg (60 mpk), or TAK-632 at 120 mg/kg (120 mpk). Tumor xenografts are obtained at indicated time points after the final treatment and analyzed by Western blot analysis. Individual blots with dividing lines are combined from a single electrophoresis gel. Bars represent densitometric analysis of phospho-ERK, normalized to vehicle-treated control (mean±SD). MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[1]. Okaniwa M, et al. Discovery of a selective kinase inhibitor (TAK-632) targeting pan-RAF inhibition: design, synthesis, and biological evaluation of C-7-substituted 1,3-benzothiazole derivatives. J Med Chem. 2013 Aug 22;56(16):6478-94. [Content Brief] [2]. Nakamura A, et al. Antitumor activity of the selective pan-RAF inhibitor TAK-632 in BRAF inhibitor-resistant melanoma. Cancer Res. 2013 Oct 11. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	1.8034 mL	9.0168 mL	18.0336 mL	45.0840 mL
	5 mM	0.3607 mL	1.8034 mL	3.6067 mL	9.0168 mL
	10 mM	0.1803 mL	0.9017 mL	1.8034 mL	4.5084 mL
	15 mM	0.1202 mL	0.6011 mL	1.2022 mL	3.0056 mL
	20 mM	0.0902 mL	0.4508 mL	0.9017 mL	2.2542 mL
	25 mM	0.0721 mL	0.3607 mL	0.7213 mL	1.8034 mL
	30 mM	0.0601 mL	0.3006 mL	0.6011 mL	1.5028 mL
	40 mM	0.0451 mL	0.2254 mL	0.4508 mL	1.1271 mL
	50 mM	0.0361 mL	0.1803 mL	0.3607 mL	0.9017 mL
	60 mM	0.0301 mL	0.1503 mL	0.3006 mL	0.7514 mL
	80 mM	0.0225 mL	0.1127 mL	0.2254 mL	0.5636 mL
	100 mM	0.0180 mL	0.0902 mL	0.1803 mL	0.4508 mL

TAK-632 Related Classifications

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

TAK-6321228591-30-7TAK632TAK 632RafAurora KinaseRaf kinasesInhibitorinhibitorinhibit

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TAK-632

Customer Review

TAK-632 Related Antibodies

4 Publications Citing Use of MCE TAK-632

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Biological Activity

Protocol

Purity & Documentation

References

Customer Review

TAK-632 Related Antibodies

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Dilution Calculator

Complete Stock Solution Preparation Table

TAK-632 Related Classifications

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