TABLE 3.

Potential therapeutic ligands targeting to GPCRs in epididymis

Receptor	Ligand	Structure (or sequence)	Mode of action	Highest status	References
ADGRG2	Tethered peptide agonist	TSFGILLDLSRTSLP	Agonist		Demberg et al. (2015) and Balenga et al. (2017)
AT2 receptor	Angiotensin II (Ang II)	Asp1‐Arg2‐Val3‐Tyr4‐Ile5‐His6‐Pro7‐Phe8	Agonist	Clinic	Guimond, Hallberg, Gallo‐Payet, and Wallinder (2014) and Hallberg, Sumners, Steckelings, and Hallberg (2018)
	Saralasin	[Sar1,Val5,Ala8]Ang II	Agonist	Clinic	Guimond et al. (2014) and Hallberg et al. (2018)
	Sarile	[Sar1,Ile8]Ang II	Agonist	Clinic	Guimond et al. (2014) and Hallberg et al. (2018)
	MP‐157	No structural formula is disclosed	Agonist	Phase 1	Hallberg et al. (2018)
	C21/M24		Agonist	Phase 2	Hallberg et al. (2018)
	C38/M132		Antagonist		Hallberg et al. (2018)
LGR4	R‐spondins	R‐spondin1‐4(RSPO1‐4)	Agonist		Carmon et al. (2011), de Lau et al. (2011), and Glinka et al. (2011)
	Norrin	MRKHVLAASFSMLSLLVIMGDTDSKTDSSFIMDSDPRRCMRHHYVDSISHPLYKCSSKMVLLARCEGHCSQASRSEPLVSFSTVLKQPFRSSCHCCRPQTSKLKALRLRCSGGMRLTATYRYILSCHCEECNS	Agonist		Deng et al. (2013)
	TNFSF11(RANKL)	Tumor necrosis factor (TNF) superfamily member 11	Agonist		Luo et al. (2016)
GPER	G‐1		Agonist		Bologa et al. (2006)
	G15		Antagonist		Dennis et al. (2009) and Dennis et al. (2011)
	G36		Antagonist		Dennis et al. (2011)
A1AR	Trabodenoson (INO‐8875)		Partial agonist	Phase 3	Jacobson, Tosh, Jain, and Gao (2019)
A2AAR	Regadenoson		Agonist		Jacobson et al. (2019)
A3AR	IB‐MECA		Agonist	Phase 3	Jacobson et al. (2019)