PPAR Inhibitors as Novel Tubulin-Targeting Agents

Table 1

Effects of PPARγ inhibitors on PPARγ, PPARα, and PPARδ activity IC50 (nM) for ability to compete with a PPAR agonist.

	Binding	Direct binding assay			Activation of GAL4 chimera			References
		PPARγ	PPARα	PPARδ	PPARγ	PPARα	PPARδ
GW9662	Irreversible				4	188	471	[7]
		5	39	1200	8	630^(1)	4100	[8]
T0070907	Irreversible	1	850	1800	1 μM completely inhibits γ with no effect on α or δ ^(2)			[9]
BADGE	Reversible	100 000			100 μM 70% inhibits γ with little or no effect on α or δ ^(2)			[10]

⁽¹⁾GW9662 is also a partial activator of PPARα with an EC50 of 22 nM [8], leading to the apparently higher concentrations of GW9662 required to inhibit PPARα than would be predicted by the direct binding assay.⁽²⁾Dose curves were not performed, but the indicated concentrations suppressed the GAL4 chimera as indicated.