Proxalutamide (GT0918)

Proxalutamide, a novel 2nd generation AR antagonist, binds to the ligand- binding domain of AR, with an IC50 of 32 nM in the AR competitive binding assays. Proxalutamide can block AR transcriptional activity, reduce AR protein levels, and obviously inhibit PCa growth in vitro. ^[1]

LNCaP cells are seeded at a density of 2×10³ cells/ well in 96-well plates and incubated overnight for attachment. LNCaP cells are treated with Proxalutamide (0.32, 0.16, 0.8, 4 and 20 mM) for 7 d. After 20 ml of MTT solution (5 mg/ml) is added and incubated for 4 h at 37 C, the medium is removed. Then 150 ml of dimethyl sulfoxide (DMSO) is added to each well to dissolve formazan crystals by constant shaking for 10 min. The plates are read at 540 nm on a microplate reader and a doseeresponse curve is used to assess IC50.

The elimination half-life of proxalutamide in rats is approximately 2 h regardless of whether it is administered by the intragastric or the intravenous route. The maximum plasma concentration of proxalutamide can reach 2 μg/mL or higher, and the oral absolute bioavailability is approximately 80%. ^[2]