Table 2.

Amino acid substitutions of phenylalanine 547, cysteines 637 and 576 near the CDDO-binding pocket increase compound inhibition of LonP1

LonP1	CDDO IC50 (μM)	Fold increase in inhibition compared with WT
WT	14.0 ± 2	-
F547A	5.9 ± 0.6 ∗∗	2.4
C576V	5.2 ± 1.5 ∗∗	2.7
C637V	3.7a	3.8
F547A/C576V	1.8 ± 0.8 ∗∗∗	7.8
F547A/C637V	1.9 ± 0.3 ∗∗∗	7.4
C576S	11.9a	1.2
C637S	3.0a	4.7

IC₅₀ values were determined from end-point ATPase assays. They were derived from the best-fit dose–response curves and are reported as the mean ± S.D. of independent experiments (N ≥ 2) except for ^a where N = 1. (∗∗p < 0.01, ∗∗∗p < 0.001 by Tukey–Kramer multiple comparison test).