TABLE 1

Ligand binding affinities, azole IC50s, and turnover numbers for CYP51 proteins

CYP51Kd (nM)IC50 (μM)Turnover no. (min−1)
SterolsAzoles
LanosterolEburicolObtusifoliolClotrimazoleFluconazoleItraconazoleKetoconazoleVoriconazoleVT-1129ClotrimazoleFluconazoleItraconazoleVoriconazoleVT-1129LanosterolEburicolObtusifoliol
CneoCYP5116,300 ± 2,80013,000 ± 1,20016,800 ± 2,1004 ± 39 ± 57 ± 36 ± 24 ± 211 ± 50.170.170.170.161.4 ± 0.26.1 ± 0.53.5 ± 0.3
CgruCYP5117,300 ± 90011,700 ± 60012,200 ± 3,00044 ± 1852 ± 1542 ± 1132 ± 1514 ± 925 ± 40.20.190.20.181.9 ± 0.37.6 ± 0.43.6 ± 0.3
CgatCYP5117,500 ± 1,90015,800 ± 1,30020,600 ± 1,00011 ± 424 ± 96 ± 25 ± 219 ± 124 ± 100.140.160.160.151.2 ± 0.23.7 ± 0.44.5 ± 0.6
HsapCYP51a18,400 ± 1,500b55 ± 5b30,400 ± 4,100b92 ± 7b42 ± 16a2,290 ± 120b4,530 ± 3001.9∼1,300b70b112∼600c22.7 ± 4.8
  • a HsapCYP51, Homo sapiens CYP51.

  • b Values were taken from Warrilow et al. (24).

  • c Thirteen percent inhibition was observed in the presence of 150 μM VT-1129.