Review of the Structural and Dynamic Mechanisms of PPARγ Partial Agonism

Table 2

Crystal structures of PPAR partial agonists.

Ligand	Ligand type	PDB	Reference	Transactivation
PA-082	Isoquinoline	2FVJ	[62]	EC50 = 260 nM; 40% efficacy
Compound 2: 3-fluoro-N-[1-(4-fluorophenyl)-3-(2-thienyl)-1H-pyrazol-5-yl]benzenesulfonamide	Sulfonamide	2G0G	[58]	IC50 = 512 nM; 31% efficacy
Compound 1: N-[1-(4-fluorophenyl)-3-(2-thienyl)-1H-pyrazol-5-yl]-3,5-bis(trifluoro- methyl)benzenesulfonamide	Sulfonamide	2G0H	[58]	IC50 = 22.7 nM; 50% efficacy
(S)-1 (LT127): 2-(4-2-[1,3-benzoxazol-2-yl(heptyl)amino]ethyl-phenoxy)-2-methyl-butanoic acid	Misc. acid (ureidofibrate derivative)	2I4Z; 2I4P	[63]	EC50 = 593 nM; 50.4% efficacy
SPPARM2	Indole	2P4Y	[50]	EC50 = 3 nM; 18% efficacy
2t	Acetamide	2POB	[64]	EC50 = 6.0 M; IC50 = 5.6 M; 54% efficacy
MRL-24	Indole	2Q5P	[47]	45% efficacy
nTZDpa	Indole	2Q5S	[47]	~20% efficacy
SR145	Indole	2Q61	[47]	~20% efficacy
SR147	Indole	2Q6R	[47]	~20% efficacy
BVT.13	Misc. acid	2Q6S	[47]	~20% efficacy
Amorfrutin 1	Misc. acid	2YFE	[65]	EC50 = 458 nM; 39% efficacy
Cerco-A	(−)-Cercosporamide derivative	3B1M	[54]	EC50 = 3.5 nM; 27% efficacy
(R)-1: (2S)-2-(biphenyl-4-yloxy)-3-phenylpropanoic acid	Misc. acid	3D6D	[66]	EC50 = 5.93 M; 24% efficacy
INT131	Sulfonamide	3FUR	[60]	EC50 = 4 nM; 30% efficacy
T2384	Sulfonamide	3K8S	[67]	EC50 = 560 nM; 25% efficacy
Compound 23	(−)-Cercosporamide derivative	3LMP	[55]	EC50 = 180 nM; 47% efficacy
TCBPA	Bisphenol	3OSI	[68]	IC50 = 6.0 M; 37% efficacy
TBBPA	Bisphenol	3OSW	[68]	IC50 = 70 nM; 37% efficacy
2l: (S)-3-(5-(2-(1H-tetrazol-5-yl)phenyl)-2,3-dihydro-1H-inden-1-yl)-2-ethyl-5-isobutyl-7-methyl-3H-imidazo[4,5-b]pyridine	Misc. pyridine	3R8A	[69]	EC50 = 212 nM; 31% efficacy
Compound 13	Benzimidazole	3S9S	[52]	pEC50 = 7.4; 75% activation
GQ-16	Thiazolidine	3T03	[61]	= 160 nM; 30% efficacy
Compound 17	(−)-Cercosporamide derivative	3V9T	[57]	EC50 = 240 nM; 22% efficacy
Compound 21	(−)-Cercosporamide derivative	3V9V	[57]	EC50 = 130 nM; 79% efficacy
Telmisartan	Benzimidazole	3VN2	[53]	EC50 = 4.5 M; 25–30% efficacy
(R)-7j: (R)-2-benzyl-3-(4-propoxy-3-((4-(pyrimidin-2-yl)benzamido)methyl)phenyl)propanoic acid	Misc. acid	3VSO	[70]	EC50 = 34.6 nM; 65% efficacy
Amorfrutin 2	Misc. acid	4A4V	[71]	EC50 = 1.2 M; 30% efficacy
Amorfrutin B	Misc. acid	4A4W	[71]	EC50 = 50 nM; 20% efficacy
Compound 15	(−)-Cercosporamide derivative	4F9M	[56]	EC50 = 12 nM; 64% efficacy
12b: imidazo[4,5-c]pyridin-4-one derivative	Misc. pyridine	4HEE	[72]	EC50 = 292 nM; 25% efficacy
GW0072	Thiazolidine	4PRG	[41]	IC50 = 110 nM; 15–20% efficacy