GW4064

GW4064 is a synthetic, non-steroidal small molecule that acts as a highly potent and selective agonist of the farnesoid X receptor (FXR, NR1H4), a nuclear receptor involved in bile acid, lipid, and glucose metabolism. It has EC50 values in the low nanomolar range (15–90 nM) for FXR activation[3][8]. GW4064 has been primarily utilized as a tool compound in preclinical research and is not considered a drug candidate due to limited solubility, potential toxicity associated with its stilbene pharmacophore, and instability under UV light[3]. It modulates a variety of hepatoprotective and metabolic pathways, including significant effects on cholesterol and triglyceride levels, improvement in insulin resistance, and protection from liver injury in animal models[3][4][6][7]. GW4064 can regulate expression of genes such as CYP3A4, BSEP, MDR2, and SHP[1][4][7]. Beyond FXR, GW4064 has been shown to interact with multiple G protein–coupled receptors, notably activating histamine H1 and H4 receptors and inhibiting the H2 receptor, highlighting potential off-target effects[5]. It is not in clinical use and is mainly used in vitro and in vivo animal studies to study FXR biology and downstream signaling[3][8].

Other names

3-(2,6-Dichlorophenyl)-4-(3'-carboxy-2-chlorostilben-4-yl)oxymethyl-5-isopropylisoxazole