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

κ receptor

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

   GtoImmuPdb view: OFF :     Currently no data for κ receptor in GtoImmuPdb

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 62,99,129
Mouse 7 380 1 A2-A3 Oprk1 opioid receptor, kappa 1 8,45,58,74,123
Rat 7 380 5q11 Oprk1 opioid receptor, kappa 1 16,56,64-65,73
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:  122
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 Affinity Units Reference
nalfurafine Hs Full agonist 10.1 pKd 120
pKd 10.1 [120]
ethyketazocine Hs Full agonist 9.4 pKd 130
pKd 9.4 [130]
enadoline Hs Full agonist 8.6 – 9.2 pKd 33
pKd 8.6 – 9.2 [33]
[3H]U69593 Hs Full agonist 8.7 – 8.8 pKd 48,79,99
pKd 8.7 – 8.8 (Kd 2x10-9 – 1.6x10-9 M) [48,79,99]
(-)-bremazocine Hs Partial agonist 10.5 pKi 112
pKi 10.5 [112]
dynorphin A {Sp: Human, Mouse, Rat} Rn Full agonist 10.0 – 10.3 pKi 56,64
pKi 10.0 – 10.3 [56,64]
ethylketocyclazocine Hs Full agonist 10.0 pKi 112
pKi 10.0 [112]
(-)-cyclazocine Hs Partial agonist 10.0 pKi 112
pKi 10.0 [112]
dynorphin A-(1-13) {Sp: Human, Mouse, Rat} Hs Full agonist 9.3 – 10.7 pKi 79,112
pKi 9.3 – 10.7 [79,112]
butorphanol Hs Partial agonist 9.9 pKi 23
pKi 9.9 (Ki 1.2x10-10 M) [23]
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 64
pKi 9.9 [64]
dynorphin-(1-11) Hs Full agonist 9.7 pKi 112
pKi 9.7 [112]
etorphine Hs Full agonist 9.7 pKi 112
pKi 9.7 [112]
GR 89696 Hs Full agonist 9.7 pKi 85
pKi 9.7 [85]
enadoline Hs Full agonist 9.6 pKi 38,71
pKi 9.6 [38,71]
probe 1.1 [PMID: 24187130] Hs Agonist 9.6 pKi 128
pKi 9.6 (Ki 2.5x10-10 M) [128]
dynorphin A {Sp: Human, Mouse, Rat} Hs Full agonist 8.3 – 10.8 pKi 79,99,112,129-130
pKi 8.3 – 10.8 [79,99,112,129-130]
dynorphin B {Sp: Human, Mouse, Rat} Rn Full agonist 9.5 pKi 64
pKi 9.5 [64]
U69593 Hs Full agonist 9.5 pKi 48,112
pKi 9.5 [48,112]
naloxone benzoylhydrazone Hs Partial agonist 9.5 pKi 112
pKi 9.5 [112]
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 128
pKi 9.5 (Ki 3.5x10-10 M) [128]
α-neoendorphin {Sp: Human, Mouse, Rat} Rn Full agonist 8.9 – 10.0 pKi 56,64
pKi 8.9 – 10.0 [56,64]
HS665 Hs Full agonist 9.3 pKi 104
pKi 9.3 (Ki 4.9x10-10 M) [104]
α-neoendorphin {Sp: Human, Mouse, Rat} Hs Full agonist 8.3 – 10.2 pKi 99,129
pKi 8.3 – 10.2 [99,129]
β-neoendorphin {Sp: Human, Mouse, Rat} Rn Full agonist 9.1 pKi 64
pKi 9.1 [64]
E2078 Hs Full agonist 9.1 pKi 86
pKi 9.1 [86]
dynorphin B {Sp: Human, Mouse, Rat} Hs Partial agonist 8.1 – 9.9 pKi 79,99,112
pKi 8.1 – 9.9 [79,99,112]
spiradoline Rn Full agonist 9.0 pKi 16
pKi 9.0 [16]
asimadoline Cp Agonist 9.0 pKi 29
pKi 9.0 (Ki 1x10-9 M) [29]
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 79,99,112,124
pKi 8.0 – 9.9 [79,99,112,124]
ethyketazocine Rn Full agonist 8.8 pKi 64
pKi 8.8 [64]
E2078 Rn Full agonist 8.8 pKi 64
pKi 8.8 [64]
ICI 204448 Rn Full agonist 8.8 pKi 16
pKi 8.8 [16]
tifluadom Hs Full agonist 8.8 pKi 130
pKi 8.8 [130]
U50488 Hs Agonist 7.8 – 9.7 pKi 14,79,99,112,119,129-130
pKi 7.8 – 9.7 [14,79,99,112,119,129-130]
cebranopadol Hs Agonist 8.6 pKi 57
pKi 8.6 (Ki 2.6x10-9 M) [57]
Description: Radioligand binding assay
hydromorphone Hs Agonist 8.6 pKi 121
pKi 8.6 (Ki 2.8x10-9 M) [121]
nalorphine Hs Partial agonist 7.9 – 9.1 pKi 112,130
pKi 7.9 – 9.1 [112,130]
U50488 Rn Partial agonist 8.2 – 8.7 pKi 16,56,64
pKi 8.2 – 8.7 [16,56,64]
U69593 Rn Full agonist 8.0 – 8.7 pKi 16,64
pKi 8.0 – 8.7 [16,64]
salvinorin A Hs Full agonist 7.8 – 8.7 pKi 11,90
pKi 7.8 – 8.7 [11,90]
BU08028 Hs Agonist 8.3 pKi 42
pKi 8.3 (Ki 5.63x10-9 M) [42]
compound 3 [PMID: 23134120] Hs Partial agonist 8.2 pKi 104
pKi 8.2 (Ki 5.9x10-9 M) [104]
(-)-pentazocine Hs Partial agonist 7.8 – 8.6 pKi 112,130
pKi 7.8 – 8.6 [112,130]
β-neoendorphin {Sp: Human, Mouse, Rat} Hs Full agonist 7.9 pKi 99
pKi 7.9 [99]
tramadol Hs Agonist 7.8 pKi 121
pKi 7.8 (Ki 1.4x10-8 M) [121]
Description: Displacement of the kappa agonist U69593 from the kappa receptor expressed in CHO cells.
normorphine Hs Full agonist 7.8 pKi 112
pKi 7.8 [112]
ADL5747 Hs Agonist 7.6 pKi 53
pKi 7.6 (Ki 2.5x10-8 M) [53]
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 130
pKi 7.4 – 7.5 [130]
ADL5859 Hs Agonist 7.4 pKi 52
pKi 7.4 (Ki 3.7x10-8 M) [52]
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 112
pKi 7.3 [112]
cebranopadol Rn Agonist 7.2 pKi 57
pKi 7.2 (Ki 6.4x10-8 M) [57]
Description: Radioligand binding assay
β-endorphin {Sp: Human} Hs Partial agonist 6.3 – 7.9 pKi 99,112
pKi 6.3 – 7.9 [99,112]
dihydromorphine Hs Partial agonist 7.1 pKi 112
pKi 7.1 [112]
fentanyl Hs Partial agonist 7.1 pKi 112
pKi 7.1 [112]
etonitazene Hs Partial agonist 6.9 pKi 112
pKi 6.9 [112]
BW373U86 Hs Agonist 6.9 pKi 52
pKi 6.9 (Ki 1.3x10-7 M) [52]
SCH221510 Hs Agonist 6.9 pKi 117
pKi 6.9 (Ki 1.31x10-7 M) [117]
Description: Radioligand binding assay
morphine Rn Partial agonist 6.7 – 7.0 pKi 16,64
pKi 6.7 – 7.0 [16,64]
β-endorphin {Sp: Human} Rn Full agonist 6.8 pKi 64
pKi 6.8 [64]
UFP-512 Hs Agonist 6.7 pKi 118
pKi 6.7 [118]
Description: Measuring displacement of [3H]-diprenorphine in vitro
hydrocodone Hs Agonist 6.6 pKi 72
pKi 6.6 (Ki 2.6x10-7 M) [72]
(-)-methadone Hs Partial agonist 6.5 pKi 112
pKi 6.5 [112]
DAMGO Hs Partial agonist 6.5 pKi 112
pKi 6.5 [112]
SR16835 Hs Agonist 6.2 pKi 113
pKi 6.2 (Ki 6.813x10-7 M) [113]
Description: Radioligand binding assay
[Leu]enkephalin {Sp: Human, Mouse, Rat} Rn Full agonist 6.0 pKi 64
pKi 6.0 [64]
[Met]enkephalin {Sp: Human, Mouse, Rat} Rn Full agonist 6.0 pKi 64
pKi 6.0 [64]
DAMGO Rn Partial agonist 5.9 pKi 64
pKi 5.9 [64]
difelikefalin Mm Agonist 10.3 pEC50 95
pEC50 10.3 (EC50 4.8x10-11 M) [95]
difelikefalin Hs Agonist 9.8 pEC50 95
pEC50 9.8 (EC50 1.6x10-10 M) [95]
HS665 Hs Full agonist 8.4 pEC50 104
pEC50 8.4 (EC50 3.62x10-9 M) [104]
Description: Measuring stimulation of [35S]GTPγS binding.
compound 3 [PMID: 23134120] Hs Partial agonist 7.5 pEC50 104
pEC50 7.5 (EC50 3.5x10-8 M) [104]
Description: Measuring stimulation of [35S]GTPγS binding.
probe 1.1 [PMID: 24187130] Hs Biased agonist 5.4 – 7.5 pEC50 128
pEC50 7.5 (EC50 3.1x10-8 M) [128]
Description: Measuring [35S]GTPγS binding
pEC50 5.4 (EC50 4.129x10-6 M) [128]
Description: Measuring βarrestin2 recruitment
probe 2.1 [PMID: 24187130] Hs Biased agonist <5.0 – 7.1 pEC50 128
pEC50 7.1 (EC50 8.47x10-8 M) [128]
Description: Measuring [35S]GTPγS binding
pEC50 <5.0 (EC50 >1x10-5 M) [128]
Description: Measuring βarrestin2 recruitment
α-neoendorphin {Sp: Human, Mouse, Rat} Mm Full agonist 10.0 pIC50 123
pIC50 10.0 [123]
dynorphin B {Sp: Human, Mouse, Rat} Mm Full agonist 10.0 pIC50 123
pIC50 10.0 [123]
dynorphin A-(1-8) {Sp: Human, Mouse, Rat} Mm Full agonist 9.7 pIC50 123
pIC50 9.7 [123]
[D-Ala2,F5,Phe4]dynorphin-(1-17)-NH2 Mm Full agonist 9.7 pIC50 123
pIC50 9.7 [123]
dynorphin-(1-17)-NH2 Mm Full agonist 9.7 pIC50 123
pIC50 9.7 [123]
(-)-bremazocine Mm Full agonist 9.5 pIC50 123
pIC50 9.5 [123]
dynorphin A {Sp: Human, Mouse, Rat} Mm Full agonist 9.4 pIC50 123
pIC50 9.4 [123]
[Met5]dynorphin-(1-17) Mm Full agonist 9.2 pIC50 123
pIC50 9.2 [123]
ethyketazocine Mm Full agonist 9.0 pIC50 123
pIC50 9.0 [123]
U50488 Mm Partial agonist 9.0 pIC50 123
pIC50 9.0 [123]
spiradoline Mm Full agonist 9.0 pIC50 123
pIC50 9.0 [123]
U69593 Mm Full agonist 8.6 pIC50 123
pIC50 8.6 [123]
ICI 204448 Mm Full agonist 8.2 pIC50 123
pIC50 8.2 [123]
[D-Ala2,F5,Phe4]dynorphin-(1-13)-NH2 Mm Full agonist 7.7 pIC50 123
pIC50 7.7 [123]
β-endorphin {Sp: Human} Mm Partial agonist 7.4 pIC50 123
pIC50 7.4 [123]
nalbuphine Mm Full agonist 7.4 pIC50 123
pIC50 7.4 [123]
pethidine Hs Agonist 5.6 pIC50 84
pIC50 5.6 (IC50 2.37x10-6 M) [84]
AR-M1000390 Hs Agonist 5.1 pIC50 4
pIC50 5.1 (IC50 7.47x10-6 M) [4]
[3H]enadoline Hs Full agonist - - 100
[100]
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 [112].

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 [72]. Similarly, we have tagged the μ receptor as the primary target of the drug hydromorphone [121].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
LY2456302 Hs Antagonist 9.1 pKB 89
pKB 9.1 (KB 8.13x10-10 M) [89]
Description: Measuring inhibition of agonist-induced [35S]GTPγS binding in vitro.
zyklophin Hs Antagonist 7.1 pKB 78
pKB 7.1 (KB 8.39x10-8 M) [78]
Description: Schild analysis of zyklophin vs. Dynorphin A-(1-13)NH2
[3H]diprenorphine Hs Antagonist 9.1 pKd 3,99
pKd 9.1 (Kd 7.94x10-10 M) [3,99]
nor-binaltorphimine Rn Antagonist 9.6 – 10.7 pKi 16,56,64
pKi 9.6 – 10.7 [16,56,64]
JDTic Hs Antagonist 9.0 – 11.2 pKi 68,110,126
pKi 11.2 (Ki 6x10-12 M) [110]
Description: Measuring antagonism of U50,488-induced [35S]GTPγS binding
pKi 9.0 – 9.4 (Ki 1x10-9 – 3.98x10-10 M) [68,110,126]
nor-binaltorphimine Hs Antagonist 8.9 – 11.0 pKi 79,83,99,112,129-130
pKi 8.9 – 11.0 [79,83,99,112,129-130]
5'-guanidinonaltrindole Hs Antagonist 9.7 – 9.9 pKi 39,79,106
pKi 9.7 – 9.9 [39,79,106]
β-FNA Hs Antagonist 9.7 pKi 112
pKi 9.7 [112]
quadazocine Hs Antagonist 9.7 pKi 112
pKi 9.7 [112]
diprenorphine Hs Antagonist 9.6 – 9.7 pKi 79,112,129-130
pKi 9.6 – 9.7 [79,112,129-130]
buprenorphine Hs Antagonist 9.1 – 10.2 pKi 112,130
pKi 9.1 – 10.2 [112,130]
nalmefene Hs Antagonist 9.5 pKi 112
pKi 9.5 [112]
LY2456302 Hs Antagonist 9.1 pKi 89
pKi 9.1 (Ki 8.07x10-10 M) [89]
AT-076 Hs Antagonist 8.9 pKi 112,126
pKi 8.9 (Ki 1.14x10-9 M) [112,126]
Description: Radioligand binding assay
naltrexone Hs Antagonist 8.4 – 9.4 pKi 79,99,112
pKi 8.4 – 9.4 [79,99,112]
BNTX Hs Antagonist 8.4 pKi 112
pKi 8.4 [112]
naltriben Hs Antagonist 8.4 pKi 112
pKi 8.4 [112]
methylnaltrexone Hs Antagonist 8.2 pKi 121
pKi 8.2 (Ki 6.3x10-9 M) [121]
naloxone Hs Antagonist 7.6 – 8.6 pKi 79,99,112,129-130
pKi 7.6 – 8.6 [79,99,112,129-130]
naltrindole Hs Antagonist 8.0 pKi 112
pKi 8.0 [112]
naltrindole Rn Antagonist 7.9 pKi 56
pKi 7.9 [56]
naloxone Rn Antagonist 7.7 – 8.0 pKi 16,56,64
pKi 7.7 – 8.0 [16,56,64]
zyklophin Hs Antagonist 7.5 pKi 78
pKi 7.5 (Ki 3.03x10-8 M) [78]
alvimopan Hs Antagonist 7.0 pKi 51
pKi 7.0 (Ki 1x10-7 M) [51]
(+)-naloxone Rn Antagonist 4.7 pKi 64
pKi 4.7 [64]
naltrexone