TABLE 3

In silico ADMEa

ParameterValue for compound
DB2104DB2131DB2161DB2171DB2186DB2187DB2191DB2192DB2212DB2217Bz
Absorption
    Caco2 cell permeability (log cm/s)1.4911.1631.7731.7651.3731.211.7731.3611.1581.3840.479
    Intestinal absorption (human) (%)94.74789.96989.4690.65990.87791.51589.4691.35390.190.96468.885
    Skin permeability (logKp)−2.763−3.167−3.118−3.092−3.214−3.012−3.118−3.238−3.198−3.23−2.893
Distribution
    Vss (human) (liters/kg)0.3455.5215.1406.1244.721−0.1155.1404.6245.5084.9890.787
    Fraction unbound (human)00.2780.2920.30.3210.0640.2920.3310.2750.3070.503
    BBB permeability0.2640.2650.2410.2540.2010.2690.2410.20.2270.213−0.619
    CNS permeability−1.013−2.778−2.687−2.687−2.691−1.639−2.687−2.691−2.782−2.737−2.995
Metabolism
    CYP2D6 substrateNoNoNoNoNoNoNoNoNoNoNo
    CYP3A4 substrateYesYesYesYesYesYesYesYesYesYesNo
    CYP1A2 inhibitorYesYesYesYesYesYesYesYesYesYesNo
    CYP2C19 inhibitorYesYesYesYesYesYesYesYesYesYesNo
    CYP2C9 inhibitorYesNoNoNoNoNoNoNoNoNoNo
    CYP2D6 inhibitorNoNoNoNoNoNoNoNoNoNoNo
    CYP3A4 inhibitorNoNoNoNoNoNoNoNoNoNoNo
Excretion
    Total clearance (ml/min/kg)3.7936.99812.02310.1628.4330.54512.0236.7146.8236.3684.217
  • a Vss, volume of distribution at steady state; BBB, blood-brain barrier; CNS, central nervous system; logKp, skin permeability constant (cm/h).