. 2019 Oct 15;22(11):735–745. doi: 10.1093/ijnp/pyz054

Table 1.

Pharmacological Properties of KOR Antagonists

KOR antagonist	Selectivity for KOR vs MOR/DOR	Functional antagonism at KOR, Kb (nM)	t_1/2 (h)	[Brain]/[plasma]
JDTic	340/4900^a	0.098 (0.069)^b	28.4^c	6.9^e
LY-2456302	30/190^a	0.813 (0.285)^b	3.8^d	4.3^f
CYM-52220	1896^g	(0.77)^g*	1.9^h	>4^h
CYM-52288	>2222^g	(4.5)^g*	1.6^h	>4^h

Abbreviations: ***

^a Receptor binding affinities (Ki, nM) of antagonists using human embryonic kidney (HEK) or Chinese hamster ovary (CHO) cells expressing human KOR, MOR, or DOR (Rorick-Kehn et al., 2014).

^b Inhibition of agonist-stimulated [35S]GTPgS binding in membranes from HEK or CHO cells expressing human KOR, MOR, or DOR (Rorick-Kehn et al., 2014).

^c Mean plasma elimination half-life of 5 mg/kg IP in rats (Owens et al., 2016).

^d Mean plasma elimination half-life of 10 mg/kg p.o. in rats (Rorick-Kehn et al., 2014).

^e Brain/plasma exposure (ng/g to ng/mL) of 5.0 mg/kg IP in rats (Owens et al., 2016).

^f Brain/plasma exposure (ng/g to ng/mL) of 1.0 mg/kg p.o. in rats (Rorick-Kehn et al., 2014).

^g From (Guerrero et al., 2019). ^g* This assay uses Tango OPRK1-bla Human Bone Osteosarcoma Epithelial Cells (U2OS) cells, which express KOR linked to a GAL4-VP16 transcription factor via a tobacco etch virus (TEV) protease site. Stimulation of the KOR by U-50488 causes migration of the β-arrestin fusion protein to the GPCR and through proteolysis liberates GAL4-VP16 from the receptor (Guerrero et al., 2010).

^h Roberts and Rosen, unpublished.