NR1H4 and atherosclerosis: The demonstrated efficacy of FXR agonists in increasing levels of circulating high density lipoprotein (HDL) and reducing serum triglycerides307 prompted researchers at Eli Lilly to develop their own FXR agonist for the treatment of dyslipidaemia and atherosclerosis.308 Building on the isoxazole template of GW4064, they replaced the central phenyl ring with a piperidine and the terminal phenyl with an indole, improving drug-likeness and resulting in LY2562175 (Fig. 31) which suffered from a loss in potency against FXR but possessed more favourable PK properties.