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. 2019 Oct 16;63(12):6477–6488. doi: 10.1021/acs.jmedchem.9b01383

Table 2. Compound Binding to CYP46A1a.

compd Kd for substrate-free CYP46A1 (M) calculated konb (M–1 s–1) experimental koff (s–1)
cholesterol 9 × 10–9c 1.3 × 106 0.012 ± 0.002
(S)-EFV 5 × 10–6d ± 0.4 × 10–6 2.2 × 106 11.2 ± 0.9
rac-3 5 × 10–6e ± 0.3 × 10–6 0.7 × 106 3.6 ± 0.2
a

Experimental data are presented as the mean ± SD of the measurements from the three independent experiments.

b

Values calculated from Kd and koff assuming Inline graphic.

c

This value comes from an apparent Kd of 80 nM 20 after the correction for HPCD binding. See Experimental Section for details.

d

This is the Kd value for titrations at 24 °C 20 because the stopped-flow experiments were conducted at 23 °C.

e

This is the Kd value for titrations at 24 °C determined in the present work in addition to the Kd value at 18 °C (Figure 3) as compared to rac-3, for the CYP46A1 active site binding and hence inhibition.