TAK-632 shows significantly improved solubility (740 μg/mL) in pH 6.8 phosphate buffer and has notable oral absorption in rats (with a 25 mg/kg dose leading to an AUC of 32.47 μg h/mL and a bioavailability of 51.7%). In dogs, a 10 mg/kg oral dose of TAK-632 demonstrates excellent oral bioavailability (108%). Following a single oral administration, TAK-632 suppresses pERK in tumors at 8 hours post-dose across a range of 1.9-24.1 mg/kg, with 9.7-24.1 mg/kg doses significantly reducing pERK levels to 11% of the control. TAK-632 shows a dose-dependent antitumor effect without major body weight loss over a dosage range of 3.9-24.1 mg/kg, achieving significant tumor shrinkage at doses of 9.7 mg/kg and 24.1 mg/kg ^[1].

When orally administered at 60 mg/kg daily or 120 mg/kg daily for 21 days, TAK-632 shows strong antitumor effectiveness against NRAS-mutant melanoma in a SK-MEL-2 xenograft model, without significant toxicity (T/C=37% and 29%, respectively, both P<0.001)^[2].

TAK-632 is a multi-target inhibitor, targeting PDGFRβ, FGFR3, GSK3β, CDK2, P38α, PDGFRα, TIE2, and CDK1 with IC50 values ranging between 120-790 nM. Additionally, it inhibits CHK1, IKKβ, and MEK1 within an IC50 span of 1400-1700 nM. Preincubation for 1 hour allows TAK-632 to inhibit BRAF and CRAF competitively to ATP, with low ATP concentration IC50s at 15 nM for BRAF and 8.1 nM for CRAF. At higher ATP concentrations, the inhibition IC50s for BRAF and CRAF increase to 58 nM and 62 nM, respectively. In HMVII cells, TAK-632 effectively inhibits pMEK and pERK with IC50 values of 49 nM and 50 nM, respectively^[1].

In terms of antiproliferative activity, TAK-632 is potent in both A375 and SK-MEL-2 cell lines, exhibiting GI50 values between 40-190 nM in A375 cells and 190-250 nM in SK-MEL-2 cells^[2].