1. unbound concentration µM
Supplementary Figure 5 a
Metabolic stability
Liver microsomes
CLH
(L/h/kg)
r, m, d, h
< 0.1, 0.37, < 0.1, 0.12
Permeability
Caco-2 cells
Papp A-B (nm/s)
efflux ratio
112
1.6
Mouse pharmacokinetics
ClB (L/h/kg)
Vss (L/kg)
F (%)
3.8
4.9 78 b
unbound concentration µM
time h
Pharmacokinetic properties of BAY (a) In vitro hepatic clearances determined with liver microsomes from rat (r), mouse (m), dog (d) and human (h); permeability/transport in Caco-2 cells; in vivo PK parameter in mouse: blood clearance (ClB), volume of distribution (Vss) and oral bioavailability (F). (b) Pharmacokinetic profiles in mouse. Unbound plasma concentrations of BAY after daily administration of 10 and 15 mg/kg to female nu/nu mice. The dashed line indicates the in vitro unbound anti-proliferative GI50 value measured in B16F10 cells. Unbound concentrations -/+ SD for 3 animals are shown. Experiments from (a) and (b) were performed as previously described [Sugawara, T., et al. BAY blocks androgen receptor mutants found in castration-resistant prostate cancer patients. Oncotarget 7, (2016).]