Table 1. Summary of the in Vitro and in Vivo Properties of CYP51 Inhibitors^j.

^aEach measurement performed in triplicate.

^bapparent K_D values (see Supporting Information).

^cEach measurement is an average of five mice treated 40 mg/kg (60% DMSO), ip, bid, for 4 days.

^dEach measurement is an average of five mice treated 25 mg/kg (20% solutol), po, bid, for 4 days.

^eEach measurement is an average of five mice treated 50 mg/kg (20% solutol), po, bid, for 4 days.

^fStability of compounds in human (h), rat (r), and mouse (m) liver microsomes as evaluated compared to the Sunitinib reference (see Supporting Information).

^gInhibition of CYPs as evaluated in human liver microsomes using selective marker substrates for each CYP (see Supporting Information).

^hLP10 was previously characterized in vivo⁵² and close LP10 analogues were assessed for stability (4–7 min in both human and mouse liver microsomes) and cross-reactivity (21–23% inhibition of 1A2; 92% for 2C9; 62–77% for 2D6; and 75–55% inhibition of 3A4) previously.⁴⁴

ⁱCompound R-2 was previously characterized structurally and in vitro.⁴⁵

^jN/D: not determined.