TABLE 4.

Some of the key antagonists at the apelin receptor and their binding affinities

MM54, an antagonist at the β-arrestin and internalization pathway, consists of a cyclized peptide based around the RPRL motif. MM54 has been tested for selectivity (Bowes et al., 2012) against over 50 GPCRs (including the most closely related angiotensin II receptor AT₁) and ion channels. ALX40-4C and protamine both consist of a series of positively charged amino acids and display low binding affinities and likely low selectivity for the apelin receptor.

Ligand	Action	Binding Affinity	Units	References
MM54	Antagonist	8.2	pKi	Macaluso et al., 2011
ALX40-4C	Antagonist	5.5	pIC50	Zhou et al., 2003b
ML221	Antagonist	—	—	Maloney et al., 2012
Protamine	Antagonist	6.4	pKi	Le Gonidec et al., 2017