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 61,98,128
Mouse 7 380 1 A2-A3 Oprk1 opioid receptor, kappa 1 8,44,57,73,122
Rat 7 380 5q11 Oprk1 opioid receptor, kappa 1 16,55,63-64,72
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:  121
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 119
pKd 10.1 [119]
ethyketazocine Hs Full agonist 9.4 pKd 129
pKd 9.4 [129]
enadoline Hs Full agonist 8.6 – 9.2 pKd 32
pKd 8.6 – 9.2 [32]
[3H]U69593 Hs Full agonist 8.7 – 8.8 pKd 47,78,98
pKd 8.7 – 8.8 (Kd 2x10-9 – 1.6x10-9 M) [47,78,98]
(-)-bremazocine Hs Partial agonist 10.5 pKi 111
pKi 10.5 [111]
dynorphin A {Sp: Human, Mouse, Rat} Rn Full agonist 10.0 – 10.3 pKi 55,63
pKi 10.0 – 10.3 [55,63]
ethylketocyclazocine Hs Full agonist 10.0 pKi 111
pKi 10.0 [111]
(-)-cyclazocine Hs Partial agonist 10.0 pKi 111
pKi 10.0 [111]
dynorphin A-(1-13) {Sp: Human, Mouse, Rat} Hs Full agonist 9.3 – 10.7 pKi 78,111
pKi 9.3 – 10.7 [78,111]
butorphanol Hs Partial agonist 9.9 pKi 22
pKi 9.9 (Ki 1.2x10-10 M) [22]
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 63
pKi 9.9 [63]
dynorphin-(1-11) Hs Full agonist 9.7 pKi 111
pKi 9.7 [111]
etorphine Hs Full agonist 9.7 pKi 111
pKi 9.7 [111]
GR 89696 Hs Full agonist 9.7 pKi 84
pKi 9.7 [84]
enadoline Hs Full agonist 9.6 pKi 37,70
pKi 9.6 [37,70]
probe 1.1 [PMID: 24187130] Hs Agonist 9.6 pKi 127
pKi 9.6 (Ki 2.5x10-10 M) [127]
dynorphin A {Sp: Human, Mouse, Rat} Hs Full agonist 8.3 – 10.8 pKi 78,98,111,128-129
pKi 8.3 – 10.8 [78,98,111,128-129]
dynorphin B {Sp: Human, Mouse, Rat} Rn Full agonist 9.5 pKi 63
pKi 9.5 [63]
U69593 Hs Full agonist 9.5 pKi 47,111
pKi 9.5 [47,111]
naloxone benzoylhydrazone Hs Partial agonist 9.5 pKi 111
pKi 9.5 [111]
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 127
pKi 9.5 (Ki 3.5x10-10 M) [127]
α-neoendorphin {Sp: Human, Mouse, Rat} Rn Full agonist 8.9 – 10.0 pKi 55,63
pKi 8.9 – 10.0 [55,63]
HS665 Hs Full agonist 9.3 pKi 103
pKi 9.3 (Ki 4.9x10-10 M) [103]
α-neoendorphin {Sp: Human, Mouse, Rat} Hs Full agonist 8.3 – 10.2 pKi 98,128
pKi 8.3 – 10.2 [98,128]
β-neoendorphin {Sp: Human, Mouse, Rat} Rn Full agonist 9.1 pKi 63
pKi 9.1 [63]
E2078 Hs Full agonist 9.1 pKi 85
pKi 9.1 [85]
dynorphin B {Sp: Human, Mouse, Rat} Hs Partial agonist 8.1 – 9.9 pKi 78,98,111
pKi 8.1 – 9.9 [78,98,111]
spiradoline Rn Full agonist 9.0 pKi 16
pKi 9.0 [16]
asimadoline Cp Agonist 9.0 pKi 28
pKi 9.0 (Ki 1x10-9 M) [28]
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 78,98,111,123
pKi 8.0 – 9.9 [78,98,111,123]
ethyketazocine Rn Full agonist 8.8 pKi 63
pKi 8.8 [63]
E2078 Rn Full agonist 8.8 pKi 63
pKi 8.8 [63]
ICI 204448 Rn Full agonist 8.8 pKi 16
pKi 8.8 [16]
tifluadom Hs Full agonist 8.8 pKi 129
pKi 8.8 [129]
U50488 Hs Agonist 7.8 – 9.7 pKi 14,78,98,111,118,128-129
pKi 7.8 – 9.7 [14,78,98,111,118,128-129]
cebranopadol Hs Agonist 8.6 pKi 56
pKi 8.6 (Ki 2.6x10-9 M) [56]
Description: Radioligand binding assay
hydromorphone Hs Agonist 8.6 pKi 120
pKi 8.6 (Ki 2.8x10-9 M) [120]
nalorphine Hs Partial agonist 7.9 – 9.1 pKi 111,129
pKi 7.9 – 9.1 [111,129]
U50488 Rn Partial agonist 8.2 – 8.7 pKi 16,55,63
pKi 8.2 – 8.7 [16,55,63]
U69593 Rn Full agonist 8.0 – 8.7 pKi 16,63
pKi 8.0 – 8.7 [16,63]
salvinorin A Hs Full agonist 7.8 – 8.7 pKi 11,89
pKi 7.8 – 8.7 [11,89]
BU08028 Hs Agonist 8.3 pKi 41
pKi 8.3 (Ki 5.63x10-9 M) [41]
compound 3 [PMID: 23134120] Hs Partial agonist 8.2 pKi 103
pKi 8.2 (Ki 5.9x10-9 M) [103]
(-)-pentazocine Hs Partial agonist 7.8 – 8.6 pKi 111,129
pKi 7.8 – 8.6 [111,129]
β-neoendorphin {Sp: Human, Mouse, Rat} Hs Full agonist 7.9 pKi 98
pKi 7.9 [98]
tramadol Hs Agonist 7.8 pKi 120
pKi 7.8 (Ki 1.4x10-8 M) [120]
Description: Displacement of the kappa agonist U69593 from the kappa receptor expressed in CHO cells.
normorphine Hs Full agonist 7.8 pKi 111
pKi 7.8 [111]
ADL5747 Hs Agonist 7.6 pKi 52
pKi 7.6 (Ki 2.5x10-8 M) [52]
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 129
pKi 7.4 – 7.5 [129]
ADL5859 Hs Agonist 7.4 pKi 51
pKi 7.4 (Ki 3.7x10-8 M) [51]
morphine Hs Partial agonist 7.3 pKi 111
pKi 7.3 [111]
cebranopadol Rn Agonist 7.2 pKi 56
pKi 7.2 (Ki 6.4x10-8 M) [56]
Description: Radioligand binding assay
β-endorphin {Sp: Human} Hs Partial agonist 6.3 – 7.9 pKi 98,111
pKi 6.3 – 7.9 [98,111]
dihydromorphine Hs Partial agonist 7.1 pKi 111
pKi 7.1 [111]
fentanyl Hs Partial agonist 7.1 pKi 111
pKi 7.1 [111]
etonitazene Hs Partial agonist 6.9 pKi 111
pKi 6.9 [111]
BW373U86 Hs Agonist 6.9 pKi 51
pKi 6.9 (Ki 1.3x10-7 M) [51]
SCH221510 Hs Agonist 6.9 pKi 116
pKi 6.9 (Ki 1.31x10-7 M) [116]
Description: Radioligand binding assay
morphine Rn Partial agonist 6.7 – 7.0 pKi 16,63
pKi 6.7 – 7.0 [16,63]
β-endorphin {Sp: Human} Rn Full agonist 6.8 pKi 63
pKi 6.8 [63]
UFP-512 Hs Agonist 6.7 pKi 117
pKi 6.7 [117]
Description: Measuring displacement of [3H]-diprenorphine in vitro
hydrocodone Hs Agonist 6.6 pKi 71
pKi 6.6 (Ki 2.6x10-7 M) [71]
(-)-methadone Hs Partial agonist 6.5 pKi 111
pKi 6.5 [111]
DAMGO Hs Partial agonist 6.5 pKi 111
pKi 6.5 [111]
SR16835 Hs Agonist 6.2 pKi 112
pKi 6.2 (Ki 6.813x10-7 M) [112]
Description: Radioligand binding assay
[Leu]enkephalin {Sp: Human, Mouse, Rat} Rn Full agonist 6.0 pKi 63
pKi 6.0 [63]
[Met]enkephalin {Sp: Human, Mouse, Rat} Rn Full agonist 6.0 pKi 63
pKi 6.0 [63]
DAMGO Rn Partial agonist 5.9 pKi 63
pKi 5.9 [63]
difelikefalin Mm Agonist 10.3 pEC50 94
pEC50 10.3 (EC50 4.8x10-11 M) [94]
difelikefalin Hs Agonist 9.8 pEC50 94
pEC50 9.8 (EC50 1.6x10-10 M) [94]
HS665 Hs Full agonist 8.4 pEC50 103
pEC50 8.4 (EC50 3.62x10-9 M) [103]
Description: Measuring stimulation of [35S]GTPγS binding.
compound 3 [PMID: 23134120] Hs Partial agonist 7.5 pEC50 103
pEC50 7.5 (EC50 3.5x10-8 M) [103]
Description: Measuring stimulation of [35S]GTPγS binding.
probe 1.1 [PMID: 24187130] Hs Biased agonist 5.4 – 7.5 pEC50 127
pEC50 7.5 (EC50 3.1x10-8 M) [127]
Description: Measuring [35S]GTPγS binding
pEC50 5.4 (EC50 4.129x10-6 M) [127]
Description: Measuring βarrestin2 recruitment
probe 2.1 [PMID: 24187130] Hs Biased agonist <5.0 – 7.1 pEC50 127
pEC50 7.1 (EC50 8.47x10-8 M) [127]
Description: Measuring [35S]GTPγS binding
pEC50 <5.0 (EC50 >1x10-5 M) [127]
Description: Measuring βarrestin2 recruitment
α-neoendorphin {Sp: Human, Mouse, Rat} Mm Full agonist 10.0 pIC50 122
pIC50 10.0 [122]
dynorphin B {Sp: Human, Mouse, Rat} Mm Full agonist 10.0 pIC50 122
pIC50 10.0 [122]
dynorphin A-(1-8) {Sp: Human, Mouse, Rat} Mm Full agonist 9.7 pIC50 122
pIC50 9.7 [122]
[D-Ala2,F5,Phe4]dynorphin-(1-17)-NH2 Mm Full agonist 9.7 pIC50 122
pIC50 9.7 [122]
dynorphin-(1-17)-NH2 Mm Full agonist 9.7 pIC50 122
pIC50 9.7 [122]
(-)-bremazocine Mm Full agonist 9.5 pIC50 122
pIC50 9.5 [122]
dynorphin A {Sp: Human, Mouse, Rat} Mm Full agonist 9.4 pIC50 122
pIC50 9.4 [122]
[Met5]dynorphin-(1-17) Mm Full agonist 9.2 pIC50 122
pIC50 9.2 [122]
ethyketazocine Mm Full agonist 9.0 pIC50 122
pIC50 9.0 [122]
U50488 Mm Partial agonist 9.0 pIC50 122
pIC50 9.0 [122]
spiradoline Mm Full agonist 9.0 pIC50 122
pIC50 9.0 [122]
U69593 Mm Full agonist 8.6 pIC50 122
pIC50 8.6 [122]
ICI 204448 Mm Full agonist 8.2 pIC50 122
pIC50 8.2 [122]
[D-Ala2,F5,Phe4]dynorphin-(1-13)-NH2 Mm Full agonist 7.7 pIC50 122
pIC50 7.7 [122]
β-endorphin {Sp: Human} Mm Partial agonist 7.4 pIC50 122
pIC50 7.4 [122]
nalbuphine Mm Full agonist 7.4 pIC50 122
pIC50 7.4 [122]
pethidine Hs Agonist 5.6 pIC50 83
pIC50 5.6 (IC50 2.37x10-6 M) [83]
AR-M1000390 Hs Agonist 5.1 pIC50 4
pIC50 5.1 (IC50 7.47x10-6 M) [4]
[3H]enadoline Hs Full agonist - - 99
[99]
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 [111].

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 [71]. Similarly, we have tagged the μ receptor as the primary target of the drug hydromorphone [120].
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 88
pKB 9.1 (KB 8.13x10-10 M) [88]
Description: Measuring inhibition of agonist-induced [35S]GTPγS binding in vitro.
zyklophin Hs Antagonist 7.1 pKB 77
pKB 7.1 (KB 8.39x10-8 M) [77]
Description: Schild analysis of zyklophin vs. Dynorphin A-(1-13)NH2
[3H]diprenorphine Hs Antagonist 9.1 pKd 3,98
pKd 9.1 (Kd 7.94x10-10 M) [3,98]
nor-binaltorphimine Rn Antagonist 9.6 – 10.7 pKi 16,55,63
pKi 9.6 – 10.7 [16,55,63]
JDTic Hs Antagonist 9.0 – 11.2 pKi 67,109,125
pKi 11.2 (Ki 6x10-12 M) [109]
Description: Measuring antagonism of U50,488-induced [35S]GTPγS binding
pKi 9.0 – 9.4 (Ki 1x10-9 – 3.98x10-10 M) [67,109,125]
nor-binaltorphimine Hs Antagonist 8.9 – 11.0 pKi 78,82,98,111,128-129
pKi 8.9 – 11.0 [78,82,98,111,128-129]
5'-guanidinonaltrindole Hs Antagonist 9.7 – 9.9 pKi 38,78,105
pKi 9.7 – 9.9 [38,78,105]
β-FNA Hs Antagonist 9.7 pKi 111
pKi 9.7 [111]
quadazocine Hs Antagonist 9.7 pKi 111
pKi 9.7 [111]
diprenorphine Hs Antagonist 9.6 – 9.7 pKi 78,111,128-129
pKi 9.6 – 9.7 [78,111,128-129]
buprenorphine Hs Antagonist 9.1 – 10.2 pKi 111,129
pKi 9.1 – 10.2 [111,129]
nalmefene Hs Antagonist 9.5 pKi 111
pKi 9.5 [111]
LY2456302 Hs Antagonist 9.1 pKi 88
pKi 9.1 (Ki 8.07x10-10 M) [88]
AT-076 Hs Antagonist 8.9 pKi 111,125
pKi 8.9 (Ki 1.14x10-9 M) [111,125]
Description: Radioligand binding assay
naltrexone Hs Antagonist 8.4 – 9.4 pKi 78,98,111
pKi 8.4 – 9.4 [78,98,111]
BNTX Hs Antagonist 8.4 pKi 111
pKi 8.4 [111]
naltriben Hs Antagonist 8.4 pKi 111
pKi 8.4 [111]
methylnaltrexone Hs Antagonist 8.2 pKi 120
pKi 8.2 (Ki 6.3x10-9 M) [120]
naloxone Hs Antagonist 7.6 – 8.6 pKi 78,98,111,128-129
pKi 7.6 – 8.6 [78,98,111,128-129]
naltrindole Hs Antagonist 8.0 pKi 111
pKi 8.0 [111]
naltrindole Rn Antagonist 7.9 pKi 55
pKi 7.9 [55]
naloxone Rn Antagonist 7.7 – 8.0 pKi 16,55,63
pKi 7.7 – 8.0 [16,55,63]
zyklophin Hs Antagonist 7.5 pKi 77
pKi 7.5 (Ki 3.03x10-8 M) [77]
alvimopan Hs Antagonist 7.0 pKi 50
pKi 7.0 (Ki 1x10-7 M) [50]
(+)-naloxone Rn Antagonist 4.7 pKi 63
pKi 4.7 [63]
naltrexone Mm Antagonist 9.2 pIC50 122
pIC50 9.2 [122]
nor-binaltorphimine