G3335

G3335 ( L-tryptophyl-L-glutamic acid) is a cell-permeable dipeptide that acts as a selective and reversible PPARγ antagonist with a Kd value of 8.34 μM for PPARγ and much lower activity at other PPAR subtypes. G3335 reversibly and competitively blocks activation of PPARγ by the PPARγ agonist rosiglitazone, and conversely, in rat astrocyte culture higher levels of rosiglitazone reduced harmful effects induced by G3335. At higher concentration G3335 may act as a PPARα agonist, interacting with the PPARα ligand binding domain with a KD of 120 μM. G3335 is reported to reduce hepatic lipid accumulation in lipid-loaded hepatocytes by activation of PPARα.