Keywords

• TAK-632
• high purity
• Chengdu Henghui Pharm Tec Co. Ltd

Quick Details

• ProName: TAK-632 high quality
• CasNo: 1228591-30-7
• Molecular Formula: C27H18F4N4O3S
• Application: For laboratory use only- not intended ...
• ProductionCapacity: Metric Ton/Day
• Purity: ≥98%
• Storage: room temperature
• LimitNum: 1 Gram

Superiority

We are a CRO company, and our Research and Development team is consisted of PhDs and Masters in chemistry and pharmacy.

We are committed to protect our customer’s privacy with the highest level of ethical standard. Our dedicated team will follow up on every order and provide instant feedback on the status to our customer.

We stand behind our product by providing a complete QA report. The test data of customer order can be provided upon request.

We make our efforts to offer customer innovative, customized, high-quality service.

Our custom manufacturing encompasses everything from pharmaceutical intermediates to API.

Details

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] 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 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. 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). 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). 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.