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[CAS NO. 1228591-30-7] TAK-632
| Ships within | Stock | Price | Qty | Total |
Please click "REQUEST A QUOTE" button if there is no stock, or you need other sizes or custom synthesis.
| Catalog: | HY-15767 |
| Brand: | MCE |
| CAS: | 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 |
3 Publications Citing Use of MCE
Summary
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
DMSO : 100 mg/mL ( 180.34 mM ; Need ultrasonic)
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 |
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1.
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2.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (4.51 mM); Clear solution
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.
- [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.
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