C5AR1 and granulomatosis with polyangiitis: Avacopan (Fig. 20b) is an orally administered allosteric antagonist of C5aR1 approved by the FDA in 2021 to treat severe autoantibody (ANCA)-ANCA-associated vasculitis (granulomatosis with polyangiitis and microscopic polyangiitis).287,288 Pharmacological studies have indicated the ability of avacopan for biased inhibition of β-arrestin coupling.289–291 The co-crystal structure of C5aR1 was reported with avacopan, highlighting the binding site outside 7TMD between helices III and V (Fig. 24a).