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(2012) suggested residues visualized as possible targets located at the active-site entrance

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Targeting inflammation and fibrosis via chemokine receptors CCR2/CCR5 Macrophages have emerged as essential players in acute and chronic liver injury and in a wide range of liver diseases including NASH216 and more recently also PSC.217 Cenicriviroc (CVC) is a dual CCR2/CCR5 chemokine receptor antagonist that is able to block CCR2/5 on macrophages and HSC (figure 3) and is currently developed as anti-inflammatory/anti-fibrotic treatment in NASH and other indications.218 Despite encouraging interim data after 1 year,219 final analysis after 2 years revealed that a no significant antifibrotic effect in NASH (table 1).220 A long-term phase 3 study (AURORA, NCT03028740) was terminated early due to lack of efficacy, but CVC is still investigated in combination strategies (eg, FXR agonist tropifexor/TANDEM trial see above)

However, their adverse effects are a major limitation associated with their clinical use