TAK632

SKU: orb1226736

Description

TAK-632 is a potent pan-Raf inhibitor with IC50 of 8.3 nM and 1.4 nM for B-Raf(wt) and C-Raf in cell-free assays, respectively, showing less or no inhibition against other tested kinases.

Key Properties

• CAS Number: 1228591-30-7
• MW: 554.52
• Purity: >98% (HPLC)
• Formula: C₂₇H₁₈F₄N₄O₃S
• SMILES: O=C(C1CC1)NC(S2)=NC3=C2C(C#N)=C(OC4=CC(NC(CC5=CC=CC(C(F)(F)F)=C5)=O)=C(F)C=C4)C=C3
• Target: Aurora Kinase
• Solubility: Ethanol: 2 mg/mL (3.6 mM); DMSO: 100 mg/mL (180.33 mM)

Bioactivity

• 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.
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• 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. 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).
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Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

TAK632, TAK 632, TAK-632

Quick Database Links

Gene Symbol

Aurora Kinase