TABLE 1

Reported bias of μ-opioid agonists from a range of published studies

Reported bias along with bias factor. For clarity, with regard to G protein signaling, only data calculated from G protein-activation assays or cAMP signaling are included.

LigandBiasBias FactorBias QuantificationAssays (receptor species)Reference LigandReference
BuprenorphineG protein69∆∆log(τ/KA)cAMP (hMOPr) vs. Arrestin-3 recruitment (hMOPr)MorphineBurgueno et al., 2017
DynA 1-6G protein4.6∆∆log(τ/KA)GTPγS (hMOPr) vs. Arrestin-3 recruitment (N.R.)DAMGO(Thompson et al., 2015b)
Endomorphin-1Arrestin; G protein0.06; 35.6∆∆log(τ/KA)GTPγS (hMOPr) vs. Arrestin-3 recruitment (N.R.); cAMP (hMOPr) vs. Arrestin-2 recruitment (N.R.)DAMGO(Thompson et al., 2015b)
ArrestinN.R.Correlation of operational efficacy (τ)GTPγS (rMOPr) vs. Arrestin-3 recruitment (N.R.)N.A.McPherson et al., 2010
ArrestinN.R.∆∆log(τ/KA)Gαi3 BRET (hMOPr) vs. Arrestin-3 recruitment (N.R.)DAMGOThompson et al., 2016
Endomorphin-2ArrestinN.R.(βlig)GTPγS (rMOPr) vs. Arrestin-3 recruitment (N.R)Leu-enkephalinRivero et al., 2012
ArrestinN.R.Correlation of operational efficacy (τ)GTPγS (rMOPr) vs. Arrestin-3 recruitment (N.R.)N.A.McPherson et al., 2010
Arrestin0.23∆∆log(τ)cAMP (hMOPr) vs. Arrestin-3 recruitment (hMOPr)MorphineBurgueno et al., 2017
G proteinN.R.∆∆log(τ/KA)cAMP (hMOPr) vs. Arrestin-3 recruitment (hMOPr)Pfizer standard 1(Hothersall et al., 2017)
FentanylArrestin; G protein0.18; 2.8∆∆log(τ/KA)GTPγS (hMOPr) vs. Arrestin-3 recruitment (hMOPr); cAMP (hMOP) vs. Arrestin-3 recruitment (hMOPr)DAMGO(Schmid et al., 2017)
Arrestin0.05; 0.15∆∆log(τ/KA)GTPγS (mMoPr) v Arrestin-3 recruitment (mMoPr); GTPγS (mMOPr (brain)) v Arrestin-3 recruitment (mMOPRr)DAMGO(Schmid et al., 2017)
G protein9.1∆∆log(τ/KA)cAMP (hMOPr) vs. Arrestin-3 recruitment (hMOPr)MorphineBurgueno et al., 2017
Arrestin0.37∆∆log(τ)cAMP (hMOPr) vs. Arrestin-3 recruitment (hMOPr)MorphineBurgueno et al., 2017
LoperamideG protein10.1; 9.4∆∆log(τ/KA)GTPγS (hMOPr) vs. Arrestin-3 recruitment (N.R.); cAMP (hMOPr) vs. Arrestin-3 recruitment (N.R.)DAMGO(Thompson et al., 2015b)
G protein18.3; 17.0∆∆log(τ/KA)GTPγS (hMOPr) vs. Arrestin-2 recruitment (N.R); cAMP (hMOPr) vs. Arrestin-2 recruitment (N.R.)DAMGO(Thompson et al., 2015b)
Met-enkephalinG proteinN.R.∆∆log(τ/KA)cAMP (hMOPr) vs. Arrestin-3 recruitment (hMOPr)Pfizer standard 1(Hothersall et al., 2017)
MorphineArrestin0.1∆∆log(τ/KA)GTPγS (hMOPr) vs. Arrestin-3 recruitment (N.R.)DAMGO(Thompson et al., 2015b)
ArrestinN.R.∆∆log(τ/KA)Gαi1 BRET (hMOPr) vs. Arrestin-3 recruitment (N.R.)DAMGOThompson et al., 2016
G protein; Arrestin1.3; 0.62∆∆log(τ/KA)GTPγS (hMOPr) vs. Arrestin-3 recruitment (hMOPr); cAMP (hMOP) vs. Arrestin-3 recruitment (hMOPr)DAMGO(Schmid et al., 2017)
G protein1.9∆∆log(τ/KA)GTPγS (mMOPR (brain)) v Arrestin-3 recruitment (mMOPr)DAMGO(Schmid et al., 2017)
SufentanilArrestin0.16∆∆log(τ/KA)GTPγS (hMOPr) vs. Arrestin-3 recruitment (hMOPr)DAMGO(Schmid et al., 2017)
Arrestin0.06; 0.14∆∆log(τ/KA)GTPγS (mMOPr) v Arrestin-3 recruitment (mMOPR); GTPγS (mMOPr (brain)) v Arrestin-3 recruitment (mMOPr)DAMGO(Schmid et al., 2017)
α-NeoG protein14.6∆∆log(τ/KA)cAMP (hMOPr) vs. Arrestin-3 recruitment (N.R.)DAMGO(Thompson et al., 2015b)
G protein8∆∆log(τ/KA)cAMP (hMOPr) vs. Arrestin-2 recruitment (N.R)DAMGO(Thompson et al., 2015b)
G proteinN.R.∆∆log(τ/KA)Gαi2 BRET (hMOPr) vs. Arrestin-3 recruitment (N.R.)DAMGOThompson et al., 2016
PZM 21G proteinN.R.∆∆log(τ/KA)cAMP vs. Arrestin-3 recruitmentN.R.Manglik et al., 2016
TRV 130G protein3RAicAMP (hMOPr) vs. Arrestin-3 recruitment (hMOPr)MorphineDewire et al., 2013
G protein4.2∆∆log(τ)cAMP (hMOPr) vs. Arrestin-3 recruitment (hMOPr)MorphineBurgueno et al., 2017
SR-15098aG protein29; 19∆∆log(τ/KA)GTPγS (hMOPr) vs. Arrestin-3 recruitment (hMOPr); cAMP (hMOP) vs. Arrestin-3 recruitment (hMOPr)DAMGO(Schmid et al., 2017)
G protein11; 55∆∆log(τ/KA)GTPγS (mMOPr) vs. Arrestin-3 recruitment (mMOPr); GTPγS (mMOPr (brain)) vs. Arrestin-3 recruitment (mMOPr)DAMGO(Schmid et al., 2017)
SR-15099G protein47; 27∆∆log(τ/KA)GTPγS (hMOPr) vs. Arrestin-3 recruitment (hMOPr); cAMP (hMOP) vs. Arrestin-3 recruitment (hMOPr)DAMGO(Schmid et al., 2017)
G protein12; 55∆∆log(τ/KA)GTPγS (mMOPr) vs. Arrestin-3 recruitment (mMOPr); GTPγS (mMOPr (brain)) vs. Arrestin-3 recruitment (mMOPr)DAMGO(Schmid et al., 2017)
SR-17018G protein85; 40∆∆log(τ/KA)GTPγS (hMOPr) vs. Arrestin-3 recruitment (hMOPr); cAMP (hMOPr) vs. Arrestin-3 recruitment (hMOPr)DAMGO(Schmid et al., 2017)
G protein30; 102∆∆log(τ/KA)GTPγS (mMOPr) vs. Arrestin-3 recruitment (mMOPr); GTPγS (mMOPr (brain)) vs. Arrestin-3 recruitment (mMOPr)DAMGO(Schmid et al., 2017)
(±) SR-11501Arrestin0.41∆∆log(τ/KA)GTPγS (hMOPr) vs. Arrestin-3 recruitment (hMOPr)DAMGO(Schmid et al., 2017)
Arrestin0.12; 0.23∆∆log(τ/KA)GTPγS (mMOPr) vs. Arrestin-3 recruitment (mMOPr); GTPγS (mMOPr (brain)) vs. Arrestin-3 recruitment (mMOPr)DAMGO(Schmid et al., 2017)
(±) SR-14968G protein36; 5.1∆∆log(τ/KA)GTPγS (hMOPr) vs. Arrestin-3 recruitment (hMOPr); cAMP (hMOP) vs. Arrestin-3 recruitment (hMOPr)DAMGO(Schmid et al., 2017)
G protein6.7; 34∆∆log(τ/KA)GTPγS (mMOPr) vs. Arrestin-3 recruitment (mMOPr); GTPγS (mMOPr (brain)) vs. Arrestin-3 recruitment (mMOPr)DAMGO(Schmid et al., 2017)
(±) SR-14969aG protein11; 2.5∆∆log(τ/KA)GTPγS (hMOPr) vs. Arrestin-3 recruitment (hMOPr); cAMP (hMOP) vs. Arrestin-3 recruitment (hMOPr)DAMGO(Schmid et al., 2017)
G protein2.9; 8.6∆∆log(τ/KA)GTPγS (mMOPr) vs. Arrestin-3 recruitment (mMOPr); GTPγS (mMOPr (brain)) vs. Arrestin-3 recruitment (mMOPr)DAMGO(Schmid et al., 2017)
  • N.A. not applicable; N.R, not reported; RAi, intrinsic relative activity.