TABLE 2

In vivo pharmacokinetic parameters following 2-mg/kg intravenous administration of aDNP or conjugate 4 to wild-type mice and receptor knockout mouse models

Mouse StrainT1/2AUC0–168ClVssAUCKO/AUCWTClKO/ClWT
hμM *hl/h/kgl/kg
aDNP
 WT19111.40.00060.150
 FcRn KO4.981.360.00920.0630.1215.3
 LDL KO1838.450.00070.1990.741.16
 MR KO24012.30.00050.1501.080.83
 ASGR1 KO33314.20.00090.1421.241.50
Conjugate 4 (total)
 WT1642.790.00270.544
 FcRn KO1.190.0960.1330.2370.0349.3
 LDL KO1184.670.00280.3761.671.04
 MR KO1041.550.00590.7590.562.18
 ASGR1 KO1973.570.00360.4561.281.33
Conjugate 4 (intact)
 WT26.30.9430.01310.277
 FcRn KO1.270.1490.08920.1640.166.81
 LDL KO38.41.300.01030.2861.380.79
 MR KO24.71.120.01170.4181.190.89
 ASGR1 KO19.91.320.00920.1741.390.70
  • Cl, clearance; KO, knockout; MR, mannose receptor; WT, wild-type.