1. MAPK/ERK Pathway
    Epigenetics
    Cell Cycle/DNA Damage
  2. Raf
    Aurora Kinase
  3. TAK-632

TAK-632 

Cat. No.: HY-15767 Purity: 99.13%
Handling Instructions

TAK-632 is a potent pan-RAF inhibitor with IC50 of 1.4, 2.4 and 8.3 nM for CRAF, BRAFV600E, BRAFWT, respectively.

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

TAK-632 Chemical Structure

TAK-632 Chemical Structure

CAS No. : 1228591-30-7

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Free Sample (0.5-1 mg)   Apply Now  
10 mM * 1 mL in DMSO USD 50 In-stock
Estimated Time of Arrival: December 31
10 mg USD 50 In-stock
Estimated Time of Arrival: December 31
50 mg USD 150 In-stock
Estimated Time of Arrival: December 31
100 mg USD 270 In-stock
Estimated Time of Arrival: December 31
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Customer Review

Based on 6 publication(s) in Google Scholar

Top Publications Citing Use of Products

    TAK-632 purchased from MCE. Usage Cited in: Br J Pharmacol. 2019 Jun;176(12):2095-2108.

    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.

    TAK-632 purchased from MCE. Usage Cited in: Br J Pharmacol. 2019 Jun;176(12):2095-2108.

    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 MCE. Usage Cited in: Br J Pharmacol. 2019 Jun;176(12):2095-2108.

    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.

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    Description

    TAK-632 is a potent pan-RAF inhibitor with IC50 of 1.4, 2.4 and 8.3 nM for CRAF, BRAFV600E, BRAFWT, respectively.

    IC50 & Target

    IC50: 1.4 nM (C-RAF), 2.4 nM (BRAFV600E), 8.3 nM (BRAFWT),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 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].

    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.

    Molecular Weight

    554.52

    Formula

    C₂₇H₁₈F₄N₄O₃S

    CAS No.

    1228591-30-7

    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 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 provided by MCE.
    References
    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 NRASQ61K 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
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    Keywords:

    TAK-632TAK632TAK 632RafAurora KinaseRaf kinasesInhibitorinhibitorinhibit

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