Darolutamide, ACS – CAS 1297538-32-9

Cell Assay: To study the antiproliferative properties of ODM–201 and ORM–15341, the VCaP cell line originally derived from a bone metastasis of a CRPC patient is used. The VCaP cell line is characterized with endogenous AR gene amplification and AR overexpression30, typical for CRPC. VCaP cells are cultured in RPMI–1640 medium and supplemented with 10% fetal bovine serum (FBS), 100 UI/mL penicillin, 100 μ g/mL streptomycin, and 4 mM VCaP.
Animal Administration: [1]To elucidate the in vivo efficacy of ODM–201 in a CRPC mouse model, castrated male nude mice with subcutaneously injected VCaP cells are treated orally with ODM–201 (50 mg/kg) once (qd) or twice daily (bid), or with enzalutamide (20 mg/kg, qd) for 37 days. The dose for enzalutamide is selected based on previously published studies 9 and our pharmacokinetic (PK) analyses which reveales that in mice the systemic exposure (AUC0–24) for this dose of enzalutamide is 2.5 times higher than that for ODM–201 (50 mg/kg, bid). Moreover, enzalutamide exhibited a long plasma half–life (18.3 hours) while the half–life of ODM–201 in mice is not optimal (1.6 hours) supporting once daily dosing for enzalutamide and higher dose and more frequent dosing for ODM–201.