κ receptor | Opioid receptors | IUPHAR/BPS Guide to PHARMACOLOGY

Top ▲

κ receptor

Target not currently curated in GtoImmuPdb

Target id: 318

Nomenclature: κ receptor

Family: Opioid receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 380 8q11.2 OPRK1 opioid receptor kappa 1 64,102,133
Mouse 7 380 1 A2-A3 Oprk1 opioid receptor, kappa 1 8,47,60,76,126
Rat 7 380 5q11 Oprk1 opioid receptor, kappa 1 16,58,66-67,75
Previous and Unofficial Names
KOR-1 | Kappa receptor | OP2 | KOP | KOPr
Database Links
Specialist databases
GPCRDB oprk_human (Hs), oprk_mouse (Mm), oprk_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the human kappa opioid receptor in complex with JDTic
PDB Id:  4DJH
Ligand:  JDTic
Resolution:  2.9Å
Species:  Human
References:  125
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the Nanobody-Stabilized Active State of the Kappa Opioid Receptor
PDB Id:  6B73
Ligand:  MP1104
Resolution:  3.1Å
Species:  Human
References:  15
Natural/Endogenous Ligands
big dynorphin {Sp: Human, Mouse, Rat}
dynorphin A-(1-13) {Sp: Human, Mouse, Rat}
dynorphin A {Sp: Human, Mouse, Rat}
dynorphin A-(1-8) {Sp: Human, Mouse, Rat}
dynorphin B {Sp: Human, Mouse, Rat}
β-endorphin {Sp: Human} , β-endorphin {Sp: Mouse} , β-endorphin {Sp: Rat}
[Leu]enkephalin {Sp: Human, Mouse, Rat}
[Met]enkephalin {Sp: Human, Mouse, Rat}
α-neoendorphin {Sp: Human, Mouse, Rat}
β-neoendorphin {Sp: Human, Mouse, Rat}
Comments: Dynorphin A and big dynorphin are the highest potency endogenous ligands
Principal endogenous agonists (Human)
big dynorphin (PDYN, P01213), dynorphin A (PDYN, P01213)

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
nalfurafine Hs Full agonist 10.1 pKd 123
pKd 10.1 [123]
ethyketazocine Hs Full agonist 9.4 pKd 134
pKd 9.4 [134]
enadoline Hs Full agonist 8.6 – 9.2 pKd 35
pKd 8.6 – 9.2 [35]
[3H]U69593 Hs Full agonist 8.7 – 8.8 pKd 50,81,102
pKd 8.7 – 8.8 (Kd 2x10-9 – 1.6x10-9 M) [50,81,102]
(-)-bremazocine Hs Partial agonist 10.5 pKi 115
pKi 10.5 [115]
dynorphin A {Sp: Human, Mouse, Rat} Rn Full agonist 10.0 – 10.3 pKi 58,66
pKi 10.0 – 10.3 [58,66]
ethylketocyclazocine Hs Full agonist 10.0 pKi 115
pKi 10.0 [115]
(-)-cyclazocine Hs Partial agonist 10.0 pKi 115
pKi 10.0 [115]
dynorphin A-(1-13) {Sp: Human, Mouse, Rat} Hs Full agonist 9.3 – 10.7 pKi 81,115
pKi 9.3 – 10.7 [81,115]
butorphanol Hs Partial agonist 9.9 pKi 24
pKi 9.9 (Ki 1.2x10-10 M) [24]
Description: Displacement of [3H]U69593 from human κ opioid receptor expressed in CHO cells.
dynorphin A-(1-13) {Sp: Human, Mouse, Rat} Rn Full agonist 9.9 pKi 66
pKi 9.9 [66]
dynorphin-(1-11) Hs Full agonist 9.7 pKi 115
pKi 9.7 [115]
etorphine Hs Full agonist 9.7 pKi 115
pKi 9.7 [115]
GR 89696 Hs Full agonist 9.7 pKi 88
pKi 9.7 [88]
enadoline Hs Full agonist 9.6 pKi 40,73
pKi 9.6 [40,73]
probe 1.1 [PMID: 24187130] Hs Agonist 9.6 pKi 132
pKi 9.6 (Ki 2.5x10-10 M) [132]
dynorphin A {Sp: Human, Mouse, Rat} Hs Full agonist 8.3 – 10.8 pKi 81,102,115,133-134
pKi 8.3 – 10.8 [81,102,115,133-134]
dynorphin B {Sp: Human, Mouse, Rat} Rn Full agonist 9.5 pKi 66
pKi 9.5 [66]
U69593 Hs Full agonist 9.5 pKi 50,115
pKi 9.5 [50,115]
naloxone benzoylhydrazone Hs Partial agonist 9.5 pKi 115
pKi 9.5 [115]
MP1104 Hs Agonist 9.5 pKi 15
pKi 9.5 (Ki 3.3x10-10 M) [15]
probe 2.1 [PMID: 24187130] Hs Agonist 9.5 pKi 132
pKi 9.5 (Ki 3.5x10-10 M) [132]
α-neoendorphin {Sp: Human, Mouse, Rat} Rn Full agonist 8.9 – 10.0 pKi 58,66
pKi 8.9 – 10.0 [58,66]
HS665 Hs Full agonist 9.3 pKi 107
pKi 9.3 (Ki 4.9x10-10 M) [107]
α-neoendorphin {Sp: Human, Mouse, Rat} Hs Full agonist 8.3 – 10.2 pKi 102,133
pKi 8.3 – 10.2 [102,133]
β-neoendorphin {Sp: Human, Mouse, Rat} Rn Full agonist 9.1 pKi 66
pKi 9.1 [66]
E2078 Hs Full agonist 9.1 pKi 89
pKi 9.1 [89]
dynorphin B {Sp: Human, Mouse, Rat} Hs Partial agonist 8.1 – 9.9 pKi 81,102,115
pKi 8.1 – 9.9 [81,102,115]
spiradoline Rn Full agonist 9.0 pKi 16
pKi 9.0 [16]
asimadoline Cp Agonist 9.0 pKi 30
pKi 9.0 (Ki 1x10-9 M) [30]
Description: Displacement of [3H]- 69593 from K opioid receptors from guinea pig cerebellum.
dynorphin A-(1-8) {Sp: Human, Mouse, Rat} Hs Full agonist 8.0 – 9.9 pKi 81,102,115,127
pKi 8.0 – 9.9 [81,102,115,127]
ethyketazocine Rn Full agonist 8.8 pKi 66
pKi 8.8 [66]
E2078 Rn Full agonist 8.8 pKi 66
pKi 8.8 [66]
ICI 204448 Rn Full agonist 8.8 pKi 16
pKi 8.8 [16]
tifluadom Hs Full agonist 8.8 pKi 134
pKi 8.8 [134]
U50488 Hs Agonist 7.8 – 9.7 pKi 14,81,102,115,122,133-134
pKi 7.8 – 9.7 [14,81,102,115,122,133-134]
cebranopadol Hs Agonist 8.6 pKi 59
pKi 8.6 (Ki 2.6x10-9 M) [59]
Description: Radioligand binding assay
hydromorphone Hs Agonist 8.6 pKi 124
pKi 8.6 (Ki 2.8x10-9 M) [124]
nalorphine Hs Partial agonist 7.9 – 9.1 pKi 115,134
pKi 7.9 – 9.1 [115,134]
U50488 Rn Partial agonist 8.2 – 8.7 pKi 16,58,66
pKi 8.2 – 8.7 [16,58,66]
U69593 Rn Full agonist 8.0 – 8.7 pKi 16,66
pKi 8.0 – 8.7 [16,66]
salvinorin A Hs Full agonist 7.8 – 8.7 pKi 11,93
pKi 7.8 – 8.7 [11,93]
BU08028 Hs Agonist 8.3 pKi 44
pKi 8.3 (Ki 5.63x10-9 M) [44]
compound 3 [PMID: 23134120] Hs Partial agonist 8.2 pKi 107
pKi 8.2 (Ki 5.9x10-9 M) [107]
(-)-pentazocine Hs Partial agonist 7.8 – 8.6 pKi 115,134
pKi 7.8 – 8.6 [115,134]
β-neoendorphin {Sp: Human, Mouse, Rat} Hs Full agonist 7.9 pKi 102
pKi 7.9 [102]
tramadol Hs Agonist 7.8 pKi 124
pKi 7.8 (Ki 1.4x10-8 M) [124]
Description: Displacement of the kappa agonist U69593 from the kappa receptor expressed in CHO cells.
normorphine Hs Full agonist 7.8 pKi 115
pKi 7.8 [115]
ADL5747 Hs Agonist 7.6 pKi 55
pKi 7.6 (Ki 2.5x10-8 M) [55]
BW373U86 Rn Agonist 7.5 pKi 12
pKi 7.5 (Ki 3.4x10-8 M) [12]
nalbuphine Hs Full agonist 7.4 – 7.5 pKi 134
pKi 7.4 – 7.5 [134]
ADL5859 Hs Agonist 7.4 pKi 54
pKi 7.4 (Ki 3.7x10-8 M) [54]
carfentanil Cp Agonist 7.4 pKi 17
pKi 7.4 (Ki 4.31x10-8 M) [17]
Description: Binding affinity- displacement of [3H]U69593 in guinea pig whole brain
morphine Hs Partial agonist 7.3 pKi 115
pKi 7.3 [115]
cebranopadol Rn Agonist 7.2 pKi 59
pKi 7.2 (Ki 6.4x10-8 M) [59]
Description: Radioligand binding assay
β-endorphin {Sp: Human} Hs Partial agonist 6.3 – 7.9 pKi 102,115
pKi 6.3 – 7.9 [102,115]
dihydromorphine Hs Partial agonist 7.1 pKi 115
pKi 7.1 [115]
fentanyl Hs Partial agonist 7.1 pKi 115
pKi 7.1 [115]
etonitazene Hs Partial agonist 6.9 pKi 115
pKi 6.9 [115]
BW373U86 Hs Agonist 6.9 pKi 54
pKi 6.9 (Ki 1.3x10-7 M) [54]
SCH221510 Hs Agonist 6.9 pKi 120
pKi 6.9 (Ki 1.31x10-7 M) [120]
Description: Radioligand binding assay
morphine Rn Partial agonist 6.7 – 7.0 pKi 16,66
pKi 6.7 – 7.0 [16,66]
β-endorphin {Sp: Human} Rn Full agonist 6.8 pKi 66
pKi 6.8 [66]
UFP-512 Hs Agonist 6.7 pKi 121
pKi 6.7 [121]
Description: Measuring displacement of [3H]-diprenorphine in vitro
hydrocodone Hs Agonist 6.6 pKi 74
pKi 6.6 (Ki 2.6x10-7 M) [74]
(-)-methadone Hs Partial agonist 6.5 pKi 115
pKi 6.5 [115]
DAMGO Hs Partial agonist 6.5 pKi 115
pKi 6.5 [115]
SR16835 Hs Agonist 6.2 pKi 116
pKi 6.2 (Ki 6.813x10-7 M) [116]
Description: Radioligand binding assay
bilorphin Hs Agonist 6.1 pKi 21
pKi 6.1 (Ki 7.7x10-7 M) [21]
[Leu]enkephalin {Sp: Human, Mouse, Rat} Rn Full agonist 6.0 pKi 66
pKi 6.0 [66]
[Met]enkephalin {Sp: Human, Mouse, Rat} Rn Full agonist 6.0 pKi 66
pKi 6.0 [66]
DAMGO Rn Partial agonist 5.9 pKi 66
pKi 5.9 [66]
difelikefalin Mm Agonist 10.3 pEC50 98
pEC50 10.3 (EC50 4.8x10-11 M) [98]
difelikefalin Hs Agonist 9.8 pEC50 98
pEC50 9.8 (EC50 1.6x10-10 M) [98]
HS665 Hs Full agonist 8.4 pEC50 107
pEC50 8.4 (EC50 3.62x10-9 M) [107]
Description: Measuring stimulation of [35S]GTPγS binding.
compound 3 [PMID: 23134120] Hs Partial agonist 7.5 pEC50 107
pEC50 7.5 (EC50 3.5x10-8 M) [107]
Description: Measuring stimulation of [35S]GTPγS binding.
probe 1.1 [PMID: 24187130] Hs Biased agonist 5.4 – 7.5 pEC50 132
pEC50 7.5 (EC50 3.1x10-8 M) [132]
Description: Measuring [35S]GTPγS binding
pEC50 5.4 (EC50 4.129x10-6 M) [132]
Description: Measuring βarrestin2 recruitment
probe 2.1 [PMID: 24187130] Hs Biased agonist 5.0 – 7.1 pEC50 132
pEC50 7.1 (EC50 8.47x10-8 M) [132]
Description: Measuring [35S]GTPγS binding
pEC50 <5.0 (EC50 >1x10-5 M) [132]
Description: Measuring βarrestin2 recruitment
α-neoendorphin {Sp: Human, Mouse, Rat} Mm Full agonist 10.0 pIC50 126
pIC50 10.0 [126]
dynorphin B {Sp: Human, Mouse, Rat} Mm Full agonist 10.0 pIC50 126
pIC50 10.0 [126]
dynorphin A-(1-8) {Sp: Human, Mouse, Rat} Mm Full agonist 9.7 pIC50 126
pIC50 9.7 [126]
[D-Ala2,F5,Phe4]dynorphin-(1-17)-NH2 Mm Full agonist 9.7 pIC50 126
pIC50 9.7 [126]
dynorphin-(1-17)-NH2 Mm Full agonist 9.7 pIC50 126
pIC50 9.7 [126]
(-)-bremazocine Mm Full agonist 9.5 pIC50 126
pIC50 9.5 [126]
dynorphin A {Sp: Human, Mouse, Rat} Mm Full agonist 9.4 pIC50 126
pIC50 9.4 [126]
[Met5]dynorphin-(1-17) Mm Full agonist 9.2 pIC50 126
pIC50 9.2 [126]
ethyketazocine Mm Full agonist 9.0 pIC50 126
pIC50 9.0 [126]
U50488 Mm Partial agonist 9.0 pIC50 126
pIC50 9.0 [126]
spiradoline Mm Full agonist 9.0 pIC50 126
pIC50 9.0 [126]
U69593 Mm Full agonist 8.6 pIC50 126
pIC50 8.6 [126]
ICI 204448 Mm Full agonist 8.2 pIC50 126
pIC50 8.2 [126]
[D-Ala2,F5,Phe4]dynorphin-(1-13)-NH2 Mm Full agonist 7.7 pIC50 126
pIC50 7.7 [126]
β-endorphin {Sp: Human} Mm Partial agonist 7.4 pIC50 126
pIC50 7.4 [126]
nalbuphine Mm Full agonist 7.4 pIC50 126
pIC50 7.4 [126]
pethidine Hs Agonist 5.6 pIC50 86
pIC50 5.6 (IC50 2.37x10-6 M) [86]
AR-M1000390 Hs Agonist 5.1 pIC50 4
pIC50 5.1 (IC50 7.47x10-6 M) [4]
[3H]enadoline Hs Full agonist - - 103
[103]
View species-specific agonist tables
Agonist Comments
Ki values were determined in the absence of Na+ and GDP, except TRK820.

Discrimination of full or partial agonism is very dependent on the level of receptor expression and on the assay used to monitor agonist effects. Many agents may behave as full agonists or potent partial agonists in cell lines expressing cloned receptors in high concentration, but in other environments they may show only weak agonist activity. The identification of agonist activity in the table is largely based on the ability to stimulate GTPγS binding in cell lines expressing cloned human kappa receptors. Agents giving 85% or greater stimulation than that given by U69593 have been characterized as Full Agonists [115].

κ opioid receptors have been divided into several different subtypes, mainly on the basis of [3H]agonist binding assays. Generally 2 subtypes are recognised: κ1 and κ2. The benzeneacetamides and peptides are considered κ1 agonists and the benzomorphans bind to κ1 and κ2. However, there is only one gene product and the subtypes are considered putative.

Selective κ agonists are of several structural types. All have high affinity for the κ receptor and are full agonists.

We have tagged the μ receptor as the primary drug target for hydrocodone based on this drug having the highest affinity at this receptor compared to the κ and δ receptors [74]. Similarly, we have tagged the μ receptor as the primary target of the drug hydromorphone [124].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
LY2456302 Hs Antagonist 9.1 pKB 92
pKB 9.1 (KB 8.13x10-10 M) [92]
Description: Measuring inhibition of agonist-induced [35S]GTPγS binding in vitro.
zyklophin Hs Antagonist 7.1 pKB 80
pKB 7.1 (KB 8.39x10-8 M) [80]
Description: Schild analysis of zyklophin vs. Dynorphin A-(1-13)NH2
[3H]diprenorphine Hs Antagonist 9.1 pKd 3,102
pKd 9.1 (Kd 7.94x10-10 M) [3,102]
nor-binaltorphimine Rn Antagonist 9.6 – 10.7 pKi 16,58,66
pKi 9.6 – 10.7 [16,58,66]
JDTic Hs Antagonist 9.0 – 11.2 pKi 70,113,129
pKi 11.2 (Ki 6x10-12 M) [113]
Description: Measuring antagonism of U50,488-induced [35S]GTPγS binding
pKi 9.0 – 9.4 (Ki 1x10-9 – 3.98x10-10 M) [70,113,129]
nor-binaltorphimine Hs Antagonist 8.9 – 11.0 pKi 81,85,102,115,133-134
pKi 8.9 – 11.0 [81,85,102,115,133-134]
5'-guanidinonaltrindole Hs Antagonist 9.7 – 9.9 pKi 41,81,109
pKi 9.7 – 9.9 [41,81,109]
β-FNA Hs Antagonist 9.7 pKi 115
pKi 9.7 [115]
quadazocine Hs Antagonist 9.7 pKi 115
pKi 9.7 [115]
diprenorphine Hs Antagonist 9.6 – 9.7 pKi 81,115,133-134
pKi 9.6 – 9.7 [81,115,133-134]
buprenorphine Hs Antagonist 9.1 – 10.2 pKi 115,134
pKi 9.1 – 10.2 [115,134]
nalmefene Hs Antagonist 9.5 pKi 115
pKi 9.5 [115]
LY2456302 Hs Antagonist 9.1 pKi 92
pKi 9.1 (Ki 8.07x10-10 M) [92]
AT-076 Hs Antagonist 8.9 pKi 115,129
pKi 8.9 (Ki 1.14x10-9 M) [115,129]
Description: Radioligand binding assay
naltrexone Hs Antagonist 8.4 – 9.4 pKi 81,102,115
pKi 8.4 – 9.4 [81,102,115]
BNTX Hs Antagonist 8.4 pKi 115
pKi 8.4 [115]
naltriben Hs Antagonist 8.4 pKi 115
pKi 8.4 [115]
NFP Hs Antagonist 8.3 pKi 131
pKi 8.3 (Ki 4.8x10-9 M) [131]
Description: In a competitive radioligand membrane binding assay measuring displacement of [3H]diprenorphine by NFP from κ receptor expressed in CHO cells.
methylnaltrexone Hs Antagonist 8.2 pKi 124
pKi 8.2 (Ki 6.3x10-9 M) [124]
naloxone Hs Antagonist 7.6 – 8.6 pKi 81,102,115,133-134
pKi 7.6 – 8.6 [81,102,115,133-134]
naltrindole Hs Antagonist 8.0