Table 2.

Structures and hPXR activities of SPA70 analogs with modifications at region B in SPA70

Compound	Region B (R2)	Bindinga (IC50/μM) (%inhibition at 10 μM)	Agonistb (EC50/μM) (%activation at 10 μM)	Inverse agonistc (IC50/μM) (%inhibition at 10 μM)	Antagonistd (IC50/μM) (%inhibition at 10 μM)
T0901317 (4)		0.036 ± 0.006 (100 ± 1)%	NTe	NT	NT
Rifampicin (1)		NT	1.4 ± 0.3 (100 ± 4)%	NA	NT
SPA70 (10)	MeO	0.19 ± 0.03 (95 ± 2)%	NAf	0.024 ± 0.007 (100 ± 3)%	0.25 ± 0.09 (100 ± 1)%
41	H	0.53 ± 0.09 (103 ± 2)%	0.8 ± 0.3 (56 ± 8)%	NA	1.0 ± 0.2 (53 ± 4%)%
42	F	0.4 ± 0.1 (80 ± 6)%	0.24 ± 0.09 (37 ± 7)%	NA	0.7 ± 0.1 (70 ± 3)%
43	Cl	0.25 ± 0.05 (94 ± 2)%	NA	0.27 ± 0.03 (62 ± 2)%	0.31 ± 0.09 (96 ± 5)%
44	Br	0.40 ± 0.03 (96 ± 3)%	NA	0.05 ± 0.03 (33 ± 4)%	0.24 ± 0.03 (99 ± 2)%
45	Me	0.8 ± 0.2 (98 ± 1)%	NA	NA	2 ± 2 (85 ± 12)%
46	CF3	0.41 ± 0.04 (90 ± 6)%	NA	NA	1.01 ± 0.06 (82 ± 4)%
47	CMe3	0.3 ± 0.2 (87 ± 1)%	0.38 ± 0.06 (113 ± 8)%	NA	NA
48	CN	0.4 ± 0.1 (98 ± 4)%	NA	0.05 ± 0.04 (34 ± 3)%	0.45 ± 0.07 (96 ± 1)%
50	CH2OH	1.4 ± 0.7 (95 ± 2)%	0.81 ± 0.02 (82 ± 5)%	NA	2.0 ± 0.3 (64 ± 7)%
51	CONH2	1.1 ± 0.1 (95 ± 1)%	2.44 ± 0.02 (182 ± 16)%	NA	NA
54 (R)		1.1 ± 0.1 (94 ± 2)%	0.44 ± 0.04 (123 ± 22)%	NA	NA
55 (S)		1.3 ± 0.4 (95 ± 1)%	0.64 ± 0.01 (112 ± 11)%	NA	NA

^aT0901317 (4) at 10 μM as 100% inhibition and DMSO (0.3%) as 0% inhibition for the hPXR binding assay;

^bRifampicin (1) at 10 μM as 100% activation and DMSO (0.3%) as 0% activation for the cell-based hPXR agonistic assay;

^cSPA70 (10) at 10 μM as 100% inhibition and DMSO (0.3%) as 0% inhibition for the cell-based hPXR inverse agonistic assay;

^dSPA70 (10) at 10 μM with rifampicin (1, 5 μM) as 100% inhibition and rifampicin alone (1, 5 μM) as 0% inhibition for the cell-based hPXR antagonistic assay;

^eNT: not tested;

^fNA: no IC₅₀ value could be experimentally determined within the concentration range tested (highest concentration tested at 30 μM).