In Vitro and In Vivo Characterizations of Chiglitazar, a Newly Identified PPAR Pan-Agonist

Table 2

In vitro transactivation activity of chiglitazar in different PPAR subtypes.

Compound	PPAR𝛼		PPAR𝛾		PPAR𝛿
	EC50 (𝜇M)	% Max^1	EC50 (𝜇M)	% Max^1	EC50 (𝜇M)	% Max^1
SMMC-7721
Chi	1.1±0.3	142	0.09±0.02	105	1.7±0.4	123
Ros	8.4±1.5	11	0.04±0.02	100	9.3±2.3	42
Pio	2.2±0.5	130	0.17±0.05	103	4.8±1.2	77
WY	15.5±2.6	100	ia	—	ia	—
2-Bro	ia^2	—	5.5±1.7	14	5.1±0.9	100
U2OS
Chi	1.2±0.3	147	0.08±0.02	117	1.5±0.2	244
Ros	7.3±1.9	16	0.04±0.02	100	13.3±3.5	42
Pio	3.2±0.7	152	0.18±0.06	91	4.8±1.3	74
WY	18.0±1.9	100	ia	—	ia	—
2-Bro	ia	—	ia	—	9.2±0.8	100

SMMC-7721 or U2OS cells were transfected individually with the expression plasmids of PPAR𝛼, 𝛾, or 𝛿, together with the reporter constructs containing the corresponding PPAR response elements. hRXR was cotransfected in all experiments. 24 h after transfection, cells were treated with the indicated compounds at various concentrations followed by the measurement of luciferase activity 24 h after treatment. The results shown are the mean values obtained from at least three independent experiments performed in triplicate normalized by the 𝛽-galactosidase reading. Chi: chiglitazar; Ros: rosiglitazone; Pio: pioglitazone; WY: WY14643; 2-Bro: 2-bromohexadecanoic acid. ¹% Max response of test compound in transactivation in subtypes 𝛼, 𝛾, and 𝛿 was compared with that of WY at 50 𝜇M, Ros at 1 𝜇M, and 2-Bro at 10 𝜇M, respectively. ²ia: inactive at 10 𝜇M.