Target Information

Target General Infomation
Target ID
T60693
Former ID
TTDS00127
Target Name
Kappa-type opioid receptor
Gene Name
OPRK1
Synonyms
KOR; KOR-1; Kappa opioid receptor; Opioid receptor Kappa; OPRK1
Target Type
Successful
Disease Alcohol use disorders [ICD9: 303; ICD10: F10.2]
Bipolar disorder [ICD9: 296.0, 296.1, 296.4, 296.5, 296.6, 296.7, 296.8, 300; ICD10: F31, F40-F42]
Coronary artery restenosis; Multiple myeloma [ICD9:203; ICD10: I51.89, C90]
Diarrhea-predominant IBS [ICD9: 564.1; ICD10: K58.0]
Erythema [ICD9: 695; ICD10: L51-L54]
Inflammatory bowel disease [ICD9: 555, 556; ICD10: K50, K51]
Neurodegenerative disease [ICD9: 330-337; ICD10: G30-G32]
Opiate dependence [ICD9: 304; ICD10: F11]
Obesity [ICD9: 278; ICD10: E66]
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89]
Substance dependence [ICD10: F10-F19]
Unspecified [ICD code not available]
Function
G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids.May play a role in arousal and regulation of autonomic and neuroendocrine functions.
BioChemical Class
GPCR rhodopsin
Target Validation
T60693
UniProt ID
P41145
Sequence
MDSPIQIFRGEPGPTCAPSACLPPNSSAWFPGWAEPDSNGSAGSEDAQLEPAHISPAIPV
IITAVYSVVFVVGLVGNSLVMFVIIRYTKMKTATNIYIFNLALADALVTTTMPFQSTVYL
MNSWPFGDVLCKIVISIDYYNMFTSIFTLTMMSVDRYIAVCHPVKALDFRTPLKAKIINI
CIWLLSSSVGISAIVLGGTKVREDVDVIECSLQFPDDDYSWWDLFMKICVFIFAFVIPVL
IIIVCYTLMILRLKSVRLLSGSREKDRNLRRITRLVLVVVAVFVVCWTPIHIFILVEALG
STSHSTAALSSYYFCIALGYTNSSLNPILYAFLDENFKRCFRDFCFPLKMRMERQSTSRV
RNTVQDPAYLRDIDGMNKPV
Drugs and Mode of Action
Drug(s) CHLOROXINE Drug Info Approved Erythema [1]
Dezocine Drug Info Approved Pain [2]
Nalbuphine Drug Info Approved Pain [3], [4]
Rapamycin Drug Info Approved Coronary artery restenosis; Multiple myeloma [5], [1]
Asimadoline Drug Info Phase 3 Diarrhea-predominant IBS [6]
Nalbuphine hydrochloride ER Drug Info Phase 3 Pain [7]
TRK-820 Drug Info Phase 3 Discovery agent [8]
CR-845 iv infusion Drug Info Phase 2/3 Pain [9]
PHN-131 Drug Info Phase 2/3 Pain [10]
Apadoline Drug Info Phase 2 Pain [11]
Carfentanil Drug Info Phase 2 Discovery agent [12]
CR-665 Drug Info Phase 2 Pain [13]
Enadoline Drug Info Phase 2 Pain [14], [15]
MAL formulation Drug Info Phase 2 Opiate dependence [16]
Niravoline Drug Info Phase 2 Pain [17]
TPM-1/Morphine Drug Info Phase 2 Pain [18]
BRL-52656 Drug Info Phase 1 Pain [19]
LY-2456302 Drug Info Phase 1 Alcohol use disorders [20]
MCP-201 Drug Info Phase 1 Pain [21]
PF-4455242 Drug Info Phase 1 Bipolar disorder [22]
GNTI Drug Info Preclinical Obesity [23]
CLIOQUINOL Drug Info Withdrawn from market Discovery agent [24]
ADL 10-0101 Drug Info Discontinued in Phase 2 Pain [25]
DYNORPHIN A Drug Info Discontinued in Phase 2 Discovery agent [26], [27]
E-2078 Drug Info Discontinued in Phase 2 Pain [28], [29]
R-84760 Drug Info Discontinued in Phase 2 Pain [30]
VP004 Drug Info Discontinued in Phase 1 Substance dependence [31]
Fedotozine Drug Info Terminated Discovery agent [32]
GR-89696 Drug Info Terminated Neurodegenerative disease [33], [34]
GR-94839 Drug Info Terminated Pain [35]
KT-95 Drug Info Terminated Inflammatory bowel disease [36]
LY-255582 Drug Info Terminated Discovery agent [37]
SB-213698 Drug Info Terminated Discovery agent [38]
Inhibitor (-)-cyclorphan Drug Info [39]
1-(1,2-diphenylethyl)-4-phenylpiperidin-4-ol Drug Info [40]
1-(2-ethoxy-1-phenylethyl)-4-phenylpiperidin-4-ol Drug Info [40]
1-(dio-tolylmethyl)-4-phenylpiperidin-4-ol Drug Info [40]
1-benzhydryl-4-(2-fluorophenyl)piperidin-4-ol Drug Info [41]
1-benzhydryl-4-(2-methoxyphenyl)piperidin-4-ol Drug Info [41]
1-benzhydryl-4-(3-fluorophenyl)piperidin-4-ol Drug Info [41]
1-benzhydryl-4-(3-methoxyphenyl)piperidin-4-ol Drug Info [41]
1-benzhydryl-4-(3-phenylpropyl)piperidin-4-ol Drug Info [41]
1-benzhydryl-4-(4-bromophenyl)piperidin-4-ol Drug Info [41]
1-benzhydryl-4-(4-chlorophenyl)piperidin-4-ol Drug Info [41]
1-benzhydryl-4-(4-ethylphenyl)piperidin-4-ol Drug Info [41]
1-benzhydryl-4-(4-fluorophenyl)piperidin-4-ol Drug Info [41]
1-benzhydryl-4-(4-methoxyphenyl)piperidin-4-ol Drug Info [41]
1-benzhydryl-4-(4-propylphenyl)piperidin-4-ol Drug Info [41]
1-benzhydryl-4-(benzyloxy)-4-phenylpiperidine Drug Info [40]
1-benzhydryl-4-(furan-2-yl)piperidin-4-ol Drug Info [41]
1-benzhydryl-4-(pyridin-2-yl)piperidin-4-ol Drug Info [41]
1-benzhydryl-4-(thiophen-2-yl)piperidin-4-ol Drug Info [41]
1-benzhydryl-4-benzylpiperidin-4-ol Drug Info [41]
1-benzhydryl-4-butylpiperidin-4-ol Drug Info [41]
1-benzhydryl-4-cyclohexylpiperidin-4-ol Drug Info [41]
1-benzhydryl-4-ethoxy-4-phenylpiperidine Drug Info [40]
1-benzhydryl-4-hexylpiperidin-4-ol Drug Info [41]
1-benzhydryl-4-isopropylpiperidin-4-ol Drug Info [41]
1-benzhydryl-4-m-tolylpiperidin-4-ol Drug Info [41]
1-benzhydryl-4-methoxy-4-phenylpiperidine Drug Info [40]
1-benzhydryl-4-o-tolylpiperidin-4-ol Drug Info [41]
1-benzhydryl-4-p-tolylpiperidin-4-ol Drug Info [41]
1-benzhydryl-4-phenyl-4-propoxypiperidine Drug Info [40]
1-benzhydryl-4-phenylpiperidin-4-ol Drug Info [42]
1-benzhydryl-4-tert-butylpiperidin-4-ol Drug Info [41]
12-EPI-SALVINORIN A Drug Info [43]
14-O-phenylpropylnaltrexone Drug Info [44]
17-(Cyclobutylmethyl)-N-phenylmorphinan-3-amine Drug Info [45]
17-(Cyclopropylmethyl)-N-phenylmorphinan-3-amine Drug Info [45]
17-methyl-4'-methyldihydromorphinone Drug Info [46]
17-Methylmorphinan-3-yl 4-Iodophenyl Carbamate Drug Info [45]
2-(2-methylquinolin-4-ylamino)-N-phenylacetamide Drug Info [47]
2-Benzylaminomethyl-3-hydroxymorphinan Drug Info [45]
2-EPI-2-THIOSALVINORIN A Drug Info [48]
2-EPI-2-THIOSALVINORIN B Drug Info [48]
2-Hydroxymethyl-3-hydroxymorphinan Drug Info [45]
2-THIOSALVINORIN B Drug Info [48]
3-(1-benzylpiperidin-4-yl)-5-chloro-1H-indole Drug Info [49]
3-(1-benzylpiperidin-4-yloxy)benzamide Drug Info [50]
3-desoxy-3-carboxamidonaltrexone Drug Info [51]
4-(4-((phenethylamino)methyl)phenoxy)benzamide Drug Info [52]
4-(p-Tolyl)spiro[chromene-2,4'-piperidine] Drug Info [53]
4-(Spiro[chromene-2,4'-piperidine]-4-yl)benzamide Drug Info [54]
4-(Spiro[chromene-2,4'-piperidine]-4-yl)phenol Drug Info [53]
4-phenyl-1-(1-phenylbutyl)piperidin-4-ol Drug Info [40]
4-phenyl-1-(1-phenylethyl)piperidin-4-ol Drug Info [40]
4-phenyl-1-(1-phenylheptyl)piperidin-4-ol Drug Info [40]
4-phenyl-1-(1-phenylhexyl)piperidin-4-ol Drug Info [40]
4-phenyl-1-(1-phenylpentyl)piperidin-4-ol Drug Info [40]
4-phenyl-1-(1-phenylpropyl)piperidin-4-ol Drug Info [40]
4-phenyl-1-(phenyl(m-tolyl)methyl)piperidin-4-ol Drug Info [40]
4-phenyl-1-(phenyl(o-tolyl)methyl)piperidin-4-ol Drug Info [40]
4-phenyl-1-(phenyl(p-tolyl)methyl)piperidin-4-ol Drug Info [40]
4-phenyl-4-[1H-imidazol-2-yl]-piperidine Drug Info [55]
4-Phenylspiro[chromene-2,4'-piperidine] Drug Info [53]
5-(4-((phenethylamino)methyl)phenoxy)picolinamide Drug Info [52]
6-(4-((benzylamino)methyl)phenoxy)nicotinamide Drug Info [52]
6-(4-((phenethylamino)methyl)phenoxy)nicotinamide Drug Info [56]
6-(4-(2-(benzylamino)ethyl)phenoxy)nicotinamide Drug Info [56]
6-(4-(3-(benzylamino)propyl)phenoxy)nicotinamide Drug Info [52]
6-(Allyl-methyl-amino)-4,4-diphenyl-heptan-3-ol Drug Info [57]
6-desoxonaltrexone Drug Info [51]
6beta-naltrexol HCl Drug Info [58]
8-azabicyclo[3.2.1]octan-3-yloxy-benzamide Drug Info [59]
8-carboxamidocyclazocine Drug Info [60]
ANISOCOUMARIN H Drug Info [61]
Benzyl derivative of M6G Drug Info [62]
Bis-((-)-N-propargylmorphinan-3-yl) sebacoylate Drug Info [39]
BUTORPHAN Drug Info [63]
CCDC 710249, HCl salt Drug Info [51]
CHLOROXINE Drug Info [64]
Cis-H-Tyr-c[D-AllylGly-Gly-Phe-D-Allylgly]-OH Drug Info [65]
CLIOQUINOL Drug Info [64]
Clocinnamox Drug Info [44]
CYCLAZOCINE Drug Info [63]
CYCLORPHAN Drug Info [63]
C[L-Ala-D-pro-L-Phe-D-trp] Drug Info [66]
C[L-mTyr-D-pro-L-Phe-D-trp] Drug Info [66]
C[L-Phe-D-pro-L-mTyr-D-trp] Drug Info [66]
C[L-Phe-D-pro-L-Phe-D-trp] Drug Info [66]
C[L-Phe-D-pro-L-Phe-L-trp] Drug Info [66]
C[L-Phe-D-pro-L-Tyr(OMe)-D-trp] Drug Info [66]
C[L-Phe-D-pro-L-Tyr-D-trp] Drug Info [66]
C[L-Tyr(OMe)-D-pro-L-Phe-D-trp] Drug Info [66]
C[L-Tyr-D-pro-L-Phe-D-trp] Drug Info [66]
DAMGO Drug Info [67]
Dcp-c[D-Cys-Gly-Phe(pNO2)-D-Cys]NH2 Drug Info [68]
Delta-kappa opioid heterodimer Drug Info [69]
DEOXY SALVINORIN A Drug Info [70]
Deprotected cogener of M6G Drug Info [62]
Dhp-c[D-Cys-Gly-Phe(pNO2)-D-Cys]NH2 Drug Info [68]
Dimepheptanol Drug Info [57]
DM6S Drug Info [67]
Dmt-Pro-3,5Dmp-Phe-NH2 Drug Info [71]
Dmt-Pro-Dmp-Phe-NH2 Drug Info [71]
Dmt-Pro-Dmt-Phe-NH2 Drug Info [71]
Dmt-Pro-Emp-Phe-NH2 Drug Info [71]
Dmt-Pro-Imp-Phe-NH2 Drug Info [71]
Dmt-Pro-Mmp-Phe-NH2 Drug Info [71]
Dmt-Pro-Phe-Phe-NH2 Drug Info [71]
Dmt-Pro-Tmp-Phe-NH2 Drug Info [71]
DPDPE Drug Info [72]
DYNORPHIN A Drug Info [73]
Dynorphin(1-8) Drug Info [74]
ELAEOCARPENINE Drug Info [75]
ENDOMORPHIN 2 Drug Info [76]
ENDOMORPHIN-1 Drug Info [76]
ETONITAZENE Drug Info [77]
FALCARINDIOL Drug Info [61]
H-Cdp-ala-Gly-Phe-leu-OH Drug Info [78]
H-Cdp-Gly-Gly-Phe-Leu-OH Drug Info [78]
H-Cpa-Gly-Gly-Phe-Met-NH2 Drug Info [78]
H-Cpa-Gly-Gly-Phe-Met-OH Drug Info [78]
H-Tyr-c[D-Allylgly-Gly-Phe-D-Allylgly]-OH Drug Info [65]
H-Tyr-c[D-Allylgly-Gly-Phe-D-Allylgly]NH2 Drug Info [79]
H-Tyr-c[D-Allylgly-Gly-Phe-L-Allylgly]NH2 Drug Info [79]
H-Tyr-c[D-Cys-Gly-Phe-D-Cys]NH2 Drug Info [79]
H-Tyr-c[D-Cys-Gly-Phe-L-Cys]NH2 Drug Info [79]
H-Tyr-Gly-Gly-Phe-Met-NH2 Drug Info [78]
HERKINORIN Drug Info [80]
HTyr-Gly-Gly-Phe-Leu-Arg-Arg-lle-Arg-Pro-LysNH2 Drug Info [81]
ICI-199441 Drug Info [82]
KETOCYCLAZOCINE Drug Info [83]
KNT-62 Drug Info [84]
KNT-63 Drug Info [84]
LOFENTANIL Drug Info [85]
LY-255582 Drug Info [86]
M3A6S Drug Info [67]
M3IBu6S Drug Info [67]
M3P6S Drug Info [67]
M3Pr6S Drug Info [67]
M6G thiosaccharide analogue Drug Info [62]
M6S Drug Info [67]
MC-CAM Drug Info [87]
MCL-117 Drug Info [39]
MCL-139 Drug Info [39]
MCL-144 Drug Info [88]
MCL-145 Drug Info [39]
MCL-147 Drug Info [89]
MCL-149 Drug Info [89]
MCL-153 Drug Info [90]
MCL-154 Drug Info [90]
MCL-182 Drug Info [89]
MCL-183 Drug Info [89]
MCL-428 Drug Info [91]
MCL-429 Drug Info [91]
MCL-431 Drug Info [91]
MCL-432 Drug Info [91]
MCL-433 Drug Info [91]
MCL-434 Drug Info [91]
MCL-435 Drug Info [91]
MCL-443 Drug Info [91]
MCL-444 Drug Info [91]
MCL-445 Drug Info [89]
MCL-446 Drug Info [89]
MCL-447 Drug Info [89]
MCL-448 Drug Info [89]
MCL-449 Drug Info [91]
MCL-450 Drug Info [92]
MCL-451 Drug Info [92]
MCL-457 Drug Info [89]
MCL-458 Drug Info [89]
METAZOCINE Drug Info [83]
MK-1925 Drug Info [93]
Morphinan Cyclic Imine analogue Drug Info [94]
MR-1029 Drug Info [95]
MR-1526 Drug Info [95]
MR-2034 Drug Info [83]
MR-2266 Drug Info [95]
N,N-diallyl[D-Pro-10]Dyn A-(1-11) Drug Info [96]
N,N-dibenzyl[D-Pro-10]Dyn A-(1-11) Drug Info [96]
N,N-diCPM[D-Pro-10]Dyn A-(1-11) Drug Info [96]
N-(17-Methylmorphinan-3-yl)-N'-phenylurea Drug Info [45]
N-(4-Iodophenyl)-N'-(17-methylmorphinan-3-yl)urea Drug Info [45]
N-allyl[D-Pro-10]Dyn A-(1-11) Drug Info [96]
N-Benzyl-17-(cyclobutylmethyl)morphinan-3-amine Drug Info [45]
N-Benzyl-17-(cyclopropylmethyl)morphinan-3-amine Drug Info [45]
N-benzyl[D-Pro-10]Dyn A-(1-11) Drug Info [96]
N-CPM[D-Pro-10]Dyn A-(1-11) Drug Info [96]
N-isobutylnoroxymorphone Drug Info [97]
NalBzOH Drug Info [67]
Naltrexone-6-alpha-ol Drug Info [83]
Naltrexone-6-beta-ol Drug Info [83]
NORBINALTORPHIMINE Drug Info [98]
Norbinaltorphimine derivative Drug Info [99]
O-DESMETHYL TRAMADOL Drug Info [83]
OXYMORPHINDOLE Drug Info [100]
Oxymorphone semicarbazone hydrochloride Drug Info [74]
PHENAZOCINE Drug Info [83]
RTI-5989-23 Drug Info [86]
RTI-5989-25 Drug Info [86]
RTI-5989-31 Drug Info [101]
Salvinicin A Drug Info [102]
SALVINICIN B Drug Info [102]
SALVINORIN A Drug Info [103]
Salvinorin A (ester) Drug Info [70]
SALVINORIN B Drug Info [80]
Salvinorin B 1-ethoxyethyl ether Drug Info [104]
Salvinorin B 2,2,2-trifluoroethoxymethyl ether Drug Info [104]
Salvinorin B 2-fluoroethoxymethyl ether Drug Info [104]
Salvinorin B 2-methoxy-2-propyl ether Drug Info [104]
Salvinorin B 2-methoxyethoxymethyl ether Drug Info [104]
Salvinorin B benzyloxymethyl ether Drug Info [104]
Salvinorin B butoxymethyl ether Drug Info [104]
Salvinorin B ethoxymethyl ether Drug Info [104]
Salvinorin B fluoromethyl ether Drug Info [104]
Salvinorin B isopropoxymethyl ether Drug Info [104]
Salvinorin B methoxymethyl ether Drug Info [104]
Salvinorin B methylthiomethyl ether Drug Info [104]
Salvinorin B propoxymethyl ether Drug Info [104]
Salvinorin B tert-butoxymethyl ether Drug Info [104]
Salvinorin B tetrahydropyran-2-yl ether Drug Info [104]
SB-213698 Drug Info [105]
SN-11 Drug Info [105]
SN-23 Drug Info [105]
SN-28 Drug Info [106]
SPIROINDANYLOXYMORPHONE Drug Info [107]
TPM-1/Morphine Drug Info [108]
Trans-H-Tyr-c[D-AllylGly-Gly-Phe-D-Allylgly]-OH Drug Info [65]
TRK-820 Drug Info [84]
U-69593 Drug Info [109]
ZYKLOPHIN Drug Info [81]
[Dcp1]Dyn A(1-11)-NH2 Drug Info [68]
[Leu5]enkephalin Drug Info [110]
Agonist 3-Methylfentanyl Drug Info [111]
3-Methylthiofentanyl Drug Info [112]
ADL 10-0101 Drug Info [113]
Apadoline Drug Info [11]
Asimadoline Drug Info [6]
BRL 52537 hydrochloride Drug Info [114]
BRL 52974 Drug Info [115]
BRL-52656 Drug Info [116]
Carfentanil Drug Info [117]
CR-665 Drug Info [118]
CR-845 iv infusion Drug Info [119]
Dihydromorphine Drug Info [120]
dynorphin B Drug Info [121]
Enadoline Drug Info [14]
ethyketazocine Drug Info [122]
ethylketocyclazocine Drug Info [123]
Fedotozine Drug Info [124]
MAL formulation Drug Info [125]
MCP-201 Drug Info [126]
Nalorphine Drug Info [127]
normorphine Drug Info [123]
NRP290 Drug Info [123]
PHN-131 Drug Info [128]
R-84760 Drug Info [129]
spiradoline Drug Info [121]
tifluadom Drug Info [122]
U50,488H Drug Info [130], [131]
[3H]enadoline Drug Info [132]
[3H]U69593 Drug Info [133]
Antagonist 5'-guanidinonaltrindole Drug Info [134]
Beta-endorphin Drug Info [135]
Dezocine Drug Info [136]
Diprenorphine Drug Info [137]
Drug 7684380 Drug Info [138]
GNTI Drug Info [23]
L-685,818 Drug Info [138]
LY-2456302 Drug Info [139]
naltriben Drug Info [123]
Nor-binaltorphimine dihydrochloride Drug Info [114]
quadazocine Drug Info [123]
Rapamycin Drug Info [140]
[3H]diprenorphine Drug Info [141]
[U-13C]ascomycin Drug Info [142]
Modulator E-2078 Drug Info [143]
GR-38414 Drug Info
GR-45809 Drug Info
GR-86014 Drug Info
GR-89696 Drug Info [144]
GR-91272 Drug Info
GR-94839 Drug Info [145]
ICI-204448 Drug Info
KT-95 Drug Info [123]
Nalbuphine Drug Info [146]
Nalbuphine hydrochloride ER Drug Info
Niravoline Drug Info
PF-4455242 Drug Info [147]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Neuroactive ligand-receptor interaction
PANTHER Pathway Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway
Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway
Opioid prodynorphin pathway
Reactome Peptide ligand-binding receptors
G alpha (i) signalling events
WikiPathways GPCRs, Class A Rhodopsin-like
Peptide GPCRs
GPCR ligand binding
GPCR downstream signaling
References
REF 1Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 2Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
REF 3FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 070692.
REF 4(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1663).
REF 5Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002452)
REF 6Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.
REF 7ClinicalTrials.gov (NCT00323154) Nalbuphine for the Treatment of Opioid Induced Pruritus in Children. U.S. National Institutes of Health.
REF 8ClinicalTrials.gov (NCT01513161) Efficacy and Safety Study of TRK-820 to Treat Conventional-treatment-resistant Pruritus in Patients Receiving Hemodialysis. U.S. National Institutes of Health.
REF 9ClinicalTrials.gov (NCT02542384) A Study Evaluating the Overall Pain Relief and Safety of Intravenous (IV) CR845 in Patients Undergoing Abdominal Surgery.
REF 10Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029095)
REF 11Novel developments with selective, non-peptidic kappa-opioid receptor agonists. Expert Opin Investig Drugs. 1997 Oct;6(10):1351-68.
REF 12ClinicalTrials.gov (NCT01899170) Towards Individualized Deep Brain Stimulation Treatment of Chronic Neuropathic Pain. U.S. National Institutes of Health.
REF 13Effect of a kappa-opioid agonist, i.v. JNJ-38488502, on sensation of colonic distensions in healthy male volunteers. Neurogastroenterol Motil. 2009 Mar;21(3):281-90.
REF 14Enadoline, a selective kappa-opioid receptor agonist shows potent antihyperalgesic and antiallodynic actions in a rat model of surgical pain. Pain. 1999 Mar;80(1-2):383-9.
REF 15(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1646).
REF 16Clinical pipeline report, company report or official report of D&A Pharma.
REF 17Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003260)
REF 18Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023017)
REF 19Opiate receptors within the blood-brain barrier mediate kappa agonist-induced water diuresis. J Pharmacol Exp Ther. 1993 Jul;266(1):164-71.
REF 20ClinicalTrials.gov (NCT02218775) FASTMAS (New Experimental Medicine Studies: Fast-Fail Trials in Mood and Anxiety Spectrum Disorders) Kappa Opioid Receptor (KOR) Phase 1 Study. U.S. National Institutes of Health.
REF 21Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018011)
REF 22ClinicalTrials.gov (NCT00988949) Proof Of Mechanism Study To Determine Efficacy Of PF-04455242 In Blocking Spiradoline (PF-00345768) Stimulated Prolactin Release. U.S. National Institutes of Health.
REF 23Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
REF 24ClinicalTrials.gov (NCT00963495) Study Evaluating the Tolerance and Biological Activity of Oral Clioquinol in Patients With Relapsed or Refractory Hematological Malignancy. U.S. National Institutes of Health.
REF 25Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011770)
REF 26(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1620).
REF 27Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005877)
REF 28(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1648).
REF 29Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003061)
REF 30Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005881)
REF 31Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025668)
REF 32Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001140)
REF 33(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1649).
REF 34Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003263)
REF 35Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003733)
REF 36Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007966)
REF 37Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005187)
REF 38Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006271)
REF 39J Med Chem. 2006 Jan 12;49(1):256-62.Synthesis and preliminary in vitro investigation of bivalent ligands containing homo- and heterodimeric pharmacophores at mu, delta, and kappa opioid receptors.
REF 40Bioorg Med Chem Lett. 2007 Jun 1;17(11):3023-7. Epub 2007 Mar 23.Synthesis and structure-activity relationships of 4-hydroxy-4-phenylpiperidines as nociceptin receptor ligands: Part 1.
REF 41Bioorg Med Chem Lett. 2007 Jun 1;17(11):3028-33. Epub 2007 Mar 21.Synthesis and structure-activity relationships of 4-hydroxy-4-phenylpiperidines as nociceptin receptor ligands: Part 2.
REF 42Bioorg Med Chem Lett. 2009 May 1;19(9):2519-23. Epub 2009 Mar 14.The discovery of tropane derivatives as nociceptin receptor ligands for the management of cough and anxiety.
REF 43Bioorg Med Chem. 2009 Feb 1;17(3):1370-80. Epub 2008 Dec 14.Modification of the furan ring of salvinorin A: identification of a selective partial agonist at the kappa opioid receptor.
REF 44J Med Chem. 2009 Mar 26;52(6):1553-7.14 beta-O-cinnamoylnaltrexone and related dihydrocodeinones are mu opioid receptor partial agonists with predominant antagonist activity.
REF 45J Med Chem. 2010 Jan 14;53(1):402-18.Synthesis and opioid receptor binding affinities of 2-substituted and 3-aminomorphinans: ligands for mu, kappa, and delta opioid receptors.
REF 46J Med Chem. 2006 Aug 24;49(17):5333-8.Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effect of substitution in the aromatic ring of cinnamoylaminomorphinones and codeinones.
REF 47Bioorg Med Chem. 2009 Aug 15;17(16):5782-90. Epub 2009 Jul 18.Synthesis and characterizations of novel quinoline derivatives having mixed ligand activities at the kappa and mu receptors: Potential therapeutic efficacy against morphine dependence.
REF 48Bioorg Med Chem Lett. 2007 Apr 15;17(8):2229-32. Epub 2007 Feb 2.Convenient synthesis and in vitro pharmacological activity of 2-thioanalogs of salvinorins A and B.
REF 49Bioorg Med Chem Lett. 2006 Jul 1;16(13):3524-8. Epub 2006 Apr 24.3-(4-Piperidinyl)indoles and 3-(4-piperidinyl)pyrrolo-[2,3-b]pyridines as ligands for the ORL-1 receptor.
REF 50Bioorg Med Chem Lett. 2010 Oct 1;20(19):5847-52. Epub 2010 Jul 30.Discovery of 8-azabicyclo[3.2.1]octan-3-yloxy-benzamides as selective antagonists of the kappa opioid receptor. Part 1.
REF 51Bioorg Med Chem Lett. 2009 Apr 15;19(8):2289-94. Epub 2009 Feb 25.Syntheses of novel high affinity ligands for opioid receptors.
REF 52Bioorg Med Chem Lett. 2007 Oct 1;17(19):5349-52. Epub 2007 Aug 11.Structure-activity relationship studies of carboxamido-biaryl ethers as opioid receptor antagonists (OpRAs). Part 1.
REF 53J Med Chem. 2008 Oct 9;51(19):5893-6. Epub 2008 Sep 13.Potent, orally bioavailable delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-4-(5-hydroxyspiro[chromene-2,4'-piperidine]-4-yl)benzamide (ADL5859).
REF 54J Med Chem. 2009 Sep 24;52(18):5685-702.Spirocyclic delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-3-hydroxy-4-(spiro[chromene-2,4'-piperidine]-4-yl) benzamide (ADL5747).
REF 55Bioorg Med Chem Lett. 2006 Jan 1;16(1):146-9. Epub 2005 Oct 19.4-Phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives, a novel class of selective delta-opioid agonists.
REF 56Bioorg Med Chem Lett. 2007 Dec 15;17(24):6841-6. Epub 2007 Oct 17.Structure activity relationship studies of carboxamido-biaryl ethers as opioid receptor antagonists (OpRAs). Part 2.
REF 57J Med Chem. 1981 Jul;24(7):903-6.Synthesis of analogues of acetylmethadol and methadol as potential narcotic antagonists.
REF 58Bioorg Med Chem Lett. 2009 May 15;19(10):2811-4. Epub 2009 Mar 26.Design, synthesis, and characterization of 6beta-naltrexol analogs, and their selectivity for in vitro opioid receptor subtypes.
REF 59Bioorg Med Chem Lett. 2010 Sep 15;20(18):5405-10. Epub 2010 Aug 3.SAR development of a series of 8-azabicyclo[3.2.1]octan-3-yloxy-benzamides as kappa opioid receptor antagonists. Part 2.
REF 60Bioorg Med Chem. 2008 May 15;16(10):5653-64. Epub 2008 Mar 30.Redefining the structure-activity relationships of 2,6-methano-3-benzazocines. Part 6: Opioid receptor binding properties of cyclic variants of 8-carboxamidocyclazocine.
REF 61Bioorg Med Chem. 2008 Mar 15;16(6):3218-23. Epub 2007 Dec 31.Novel coumarin glycoside and phenethyl vanillate from Notopterygium forbesii and their binding affinities for opioid and dopamine receptors.
REF 62Bioorg Med Chem Lett. 2005 Mar 15;15(6):1583-6.Synthesis and in vitro biological evaluation of a carbon glycoside analogue of morphine-6-glucuronide.
REF 63J Med Chem. 2000 Jan 13;43(1):114-22.Synthesis and opioid receptor affinity of morphinan and benzomorphan derivatives: mixed kappa agonists and mu agonists/antagonists as potential pharmacotherapeutics for cocaine dependence.
REF 64Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6. Epub 2010 Oct 21.In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2).
REF 65J Med Chem. 2007 Jun 28;50(13):3138-42. Epub 2007 Jun 1.Synthesis of stable and potent delta/mu opioid peptides: analogues of H-Tyr-c[D-Cys-Gly-Phe-D-Cys]-OH by ring-closing metathesis.
REF 66Bioorg Med Chem Lett. 2009 Jul 1;19(13):3647-50. Epub 2009 May 3.Nascent structure-activity relationship study of a diastereomeric series of kappa opioid receptor antagonists derived from CJ-15,208.
REF 67Bioorg Med Chem Lett. 2006 Aug 15;16(16):4291-5. Epub 2006 Jun 13.Opiate receptor binding properties of morphine-, dihydromorphine-, and codeine 6-O-sulfate ester congeners.
REF 68J Med Chem. 2006 Aug 24;49(17):5382-5.Replacement of the N-terminal tyrosine residue in opioid peptides with 3-(2,6-dimethyl-4-carbamoylphenyl)propanoic acid (Dcp) results in novel opioid antagonists.
REF 69J Med Chem. 2004 Jun 3;47(12):2969-72.A bivalent ligand (KDN-21) reveals spinal delta and kappa opioid receptors are organized as heterodimers that give rise to delta(1) and kappa(2) phenotypes. Selective targeting of delta-kappa heterodimers.
REF 70Bioorg Med Chem Lett. 2006 Sep 1;16(17):4679-85. Epub 2006 Jun 13.Synthesis and in vitro evaluation of salvinorin A analogues: effect of configuration at C(2) and substitution at C(18).
REF 71J Med Chem. 2007 Jun 14;50(12):2753-66. Epub 2007 May 12.Bifunctional [2',6'-dimethyl-L-tyrosine1]endomorphin-2 analogues substituted at position 3 with alkylated phenylalanine derivatives yield potent mixed mu-agonist/delta-antagonist and dual mu-agonist/delta-agonist opioid ligands.
REF 72J Med Chem. 1992 Nov 13;35(23):4325-9.Opioid agonist and antagonist activities of morphindoles related to naltrindole.
REF 73Bioorg Med Chem Lett. 2008 Jun 15;18(12):3667-71. Epub 2007 Dec 4.Use of receptor chimeras to identify small molecules with high affinity for the dynorphin A binding domain of the kappa opioid receptor.
REF 74J Med Chem. 1986 Jul;29(7):1222-5.Peptides as receptor selectivity modulators of opiate pharmacophores.
REF 75Bioorg Med Chem Lett. 2010 Mar 1;20(5):1601-3. Epub 2010 Jan 22.Synthesis and evaluation of opioid receptor-binding affinity of elaeocarpenine and its analogs.
REF 76J Med Chem. 2004 Jan 29;47(3):735-43.Structure-activity study on the Phe side chain arrangement of endomorphins using conformationally constrained analogues.
REF 77J Med Chem. 1990 Sep;33(9):2456-64.Photoactivatable opiate derivatives as irreversible probes of the mu-opioid receptor.
REF 78Bioorg Med Chem Lett. 2007 May 1;17(9):2656-60. Epub 2007 Feb 2.Further studies of tyrosine surrogates in opioid receptor peptide ligands.
REF 79J Med Chem. 2007 Mar 22;50(6):1414-7. Epub 2007 Feb 22.Dicarba analogues of the cyclic enkephalin peptides H-Tyr-c[D-Cys-Gly-Phe-D(or L)-Cys]NH(2) retain high opioid activity.
REF 80J Med Chem. 2008 Apr 24;51(8):2421-31. Epub 2008 Apr 2.Herkinorin analogues with differential beta-arrestin-2 interactions.
REF 81J Med Chem. 2009 Nov 12;52(21):6814-21.The effects of C-terminal modifications on the opioid activity of [N-benzylTyr(1)]dynorphin A-(1-11) analogues.
REF 82J Med Chem. 1996 Apr 12;39(8):1729-35.Arylacetamide-derived fluorescent probes: synthesis, biological evaluation, and direct fluorescent labeling of kappa opioid receptors in mouse microglial cells.
REF 83Bioorg Med Chem Lett. 2009 Jan 1;19(1):203-8. Epub 2008 Nov 7.Syntheses and opioid receptor binding properties of carboxamido-substituted opioids.
REF 84Bioorg Med Chem Lett. 2010 Jan 1;20(1):121-4. Epub 2009 Nov 13.Drug design and synthesis of a novel kappa opioid receptor agonist with an oxabicyclo[2.2.2]octane skeleton and its pharmacology.
REF 85J Med Chem. 1982 Aug;25(8):913-9.Potential affinity labels for the opiate receptor based on fentanyl and related compounds.
REF 86J Med Chem. 1998 May 21;41(11):1980-90.Investigation of the N-substituent conformation governing potency and mu receptor subtype-selectivity in (+)-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine opioid antagonists.
REF 87J Med Chem. 2009 Nov 12;52(21):6926-30.14beta-Arylpropiolylamino-17-cyclopropylmethyl-7,8-dihydronormorphinones and related opioids. Further examples of pseudoirreversible mu opioid receptor antagonists.
REF 88J Med Chem. 2009 Dec 10;52(23):7389-96.Univalent and bivalent ligands of butorphan: characteristics of the linking chain determine the affinity and potency of such opioid ligands.
REF 89Bioorg Med Chem. 2007 Jun 15;15(12):4106-12. Epub 2007 Mar 30.In-vitro investigation of oxazol and urea analogues of morphinan at opioid receptors.
REF 90Bioorg Med Chem Lett. 2010 Mar 1;20(5):1507-9. Epub 2010 Jan 25.Effect of linker substitution on the binding of butorphan univalent and bivalent ligands to opioid receptors.
REF 91Bioorg Med Chem Lett. 2007 Mar 15;17(6):1508-11. Epub 2007 Jan 17.High-affinity carbamate analogues of morphinan at opioid receptors.
REF 92J Med Chem. 2006 Sep 7;49(18):5640-3.New opioid designed multiple ligand from Dmt-Tic and morphinan pharmacophores.
REF 93Bioorg Med Chem Lett. 2009 Aug 15;19(16):4729-32. Epub 2009 Jun 17.Identification of MK-1925: a selective, orally active and brain-penetrable opioid receptor-like 1 (ORL1) antagonist.
REF 94Morphinan cyclic imines and pyrrolidines containing a constrained phenyl group: High affinity opioid agonists, Bioorg. Med. Chem. Lett. 5(24):2969-2974 (1995).
REF 95J Med Chem. 1991 Aug;34(8):2438-44.Electrophilic gamma-lactone kappa-opioid receptor probes. Analogues of 2'-hydroxy-2-tetrahydrofurfuryl-5,9-dimethyl-6,7-benzomorphan diastereomers.
REF 96J Med Chem. 1997 Aug 15;40(17):2733-9.Synthesis and opioid activity of [D-Pro10]dynorphin A-(1-11) analogues with N-terminal alkyl substitution.
REF 97Bioorg Med Chem Lett. 2008 Sep 15;18(18):4978-81. Epub 2008 Aug 12.Synthesis of N-isobutylnoroxymorphone from naltrexone by a selective cyclopropane ring opening reaction.
REF 98Bioorg Med Chem Lett. 2010 Sep 1;20(17):5035-8. Epub 2010 Jul 13.Synthesis of pyrrolomorphinan derivatives as kappa opioid agonists.
REF 99J Med Chem. 2005 Mar 10;48(5):1676-9.Major effect of pyrrolic N-benzylation in norbinaltorphimine, the selective kappa-opioid receptor antagonist.
REF 100Eur J Med Chem. 2008 Nov;43(11):2307-15. Epub 2008 Feb 29.Ligand binding to nucleic acids and proteins: Does selectivity increase with strength?.
REF 101J Med Chem. 2007 Aug 9;50(16):3765-76. Epub 2007 Jul 11.Probes for narcotic receptor mediated phenomena. 34. Synthesis and structure-activity relationships of a potent mu-agonist delta-antagonist and an exceedingly potent antinociceptive in the enantiomeric C9-substituted 5-(3-hydroxyphenyl)-N-phenylethylmorphan series.
REF 102J Med Chem. 2007 Jul 26;50(15):3596-603. Epub 2007 Jun 20.Synthetic studies of neoclerodane diterpenes from Salvia divinorum: preparation and opioid receptor activity of salvinicin analogues.
REF 103J Med Chem. 2008 Mar 27;51(6):1824-30. Epub 2008 Feb 23.Toward a structure-based model of salvinorin A recognition of the kappa-opioid receptor.
REF 104Bioorg Med Chem. 2008 Feb 1;16(3):1279-86. Epub 2007 Oct 24.Standard protecting groups create potent and selective kappa opioids: salvinorin B alkoxymethyl ethers.
REF 105Bioorg Med Chem Lett. 2009 May 15;19(10):2792-5. Epub 2009 Mar 26.Design and synthesis of novel delta opioid receptor agonists and their pharmacologies.
REF 106Bioorg Med Chem Lett. 2010 Nov 1;20(21):6302-5. Epub 2010 Aug 21.Design and synthesis of KNT-127, a |A-opioid receptor agonist effective by systemic administration.
REF 107Bioorg Med Chem. 2009 Aug 15;17(16):5983-8. Epub 2009 Jul 3.Aerobic oxidation of indolomorphinan without the 4,5-epoxy bridge and subsequent rearrangement of the oxidation product to spiroindolinonyl-C-normorphinan derivative.
REF 108Molecular Mechanisms of Opioid Receptor-Dependent Signaling and Behavior. Anesthesiology. 2011 December; 115(6): 1363-1381.
REF 109J Med Chem. 2010 May 27;53(10):4212-22.Conformationally constrained kappa receptor agonists: stereoselective synthesis and pharmacological evaluation of 6,8-diazabicyclo[3.2.2]nonane derivatives.
REF 110J Med Chem. 2010 Apr 8;53(7):2875-81."Carba"-analogues of fentanyl are opioid receptor agonists.
REF 111Subramanian G, Paterlini MG, Portoghese PS, Ferguson DM: Molecular docking reveals a novel binding site model for fentanyl at the mu-opioid receptor. J Med Chem. 2000 Feb 10;43(3):381-91.
REF 112You HJ, Colpaert FC, Arendt-Nielsen L: The novel analgesic and high-efficacy 5-HT1A receptor agonist F 13640 inhibits nociceptive responses, wind-up, and after-discharges in spinal neurons and withdrawal reflexes. Exp Neurol. 2005 Jan;191(1):174-83.
REF 113Analgesia from a peripherally active kappa-opioid receptor agonist in patients with chronic pancreatitis. Pain. 2003 Jan;101(1-2):89-95.
REF 114Kappa-opioid receptor selectivity for ischemic neuroprotection with BRL 52537 in rats. Anesth Analg. 2003 Dec;97(6):1776-83.
REF 115The antitussive activity of delta-opioid receptor stimulation in guinea pigs. J Pharmacol Exp Ther. 2000 Feb;292(2):803-9.
REF 116Kappa-opioid receptors behind the blood-brain barrier are involved in the anti-hypertensive effects of systemically administered kappa-agonists in the conscious spontaneously hypertensive rat. J Pharm Pharmacol. 1999 Nov;51(11):1251-6.
REF 117Wax PM, Becker CE, Curry SC: Unexpected “gas” casualties in Moscow: a medical toxicology perspective. Ann Emerg Med. 2003 May;41(5):700-5.
REF 118Analgesic efficacy of peripheral kappa-opioid receptor agonist CR665 compared to oxycodone in a multi-modal, multi-tissue experimental human pain model: selective effect on visceral pain. Anesthesiology. 2009 Sep;111(3):616-24.
REF 119Peptide Kappa Opioid Receptor Ligands: Potential for Drug Development. AAPS J. 2009 June; 11(2): 312-322.
REF 120Opiate receptor binding properties of morphine-, dihydromorphine-, and codeine 6-O-sulfate ester congeners. Bioorg Med Chem Lett. 2006 Aug 15;16(16):4291-5. Epub 2006 Jun 13.
REF 121Cloning and functional comparison of kappa and delta opioid receptors from mouse brain. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6736-40.
REF 122Activation of the cloned human kappa opioid receptor by agonists enhances [35S]GTPgammaS binding to membranes: determination of potencies and efficacies of ligands. J Pharmacol Exp Ther. 1997 Aug;282(2):676-84.
REF 123(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 318).
REF 124Irritable bowel syndrome neuropharmacology. A review of approved and investigational compounds. J Clin Gastroenterol. 2002 Jul;35(1 Suppl):S58-67.
REF 125Clinical pipeline report, company report or official report of D&A Pharma.
REF 126US patent application no. 6,924,288, Enantiomerically pure opioid diarylmethylpiperzine and methods of using same.
REF 127Apparent efficacy of kappa-opioid receptor ligands on serum prolactin levels in rhesus monkeys. Eur J Pharmacol. 1999 Nov 3;383(3):305-9.
REF 128Nalbuphine: an autoradiographic opioid receptor binding profile in the central nervous system of an agonist/antagonist analgesic. J Pharmacol Exp Ther. 1988 Jan;244(1):391-402.
REF 129Effects of R-84760, a selective kappa-opioid receptor agonist, on nociceptive reflex in isolated neonatal rat spinal cord. Eur J Pharmacol. 1998 Feb 19;343(2-3):171-7.
REF 130Effects of kappa- and mu-opioid receptor agonists on Ca2+ channels in neuroblastoma cells: involvement of the orphan opioid receptor. Eur J Pharmacol. 1999 Aug 27;379(2-3):191-8.
REF 131The selective kappa-opioid receptor agonist U50,488H attenuates voluntary ethanol intake in the rat. Behav Brain Res. 2001 May;120(2):137-46.
REF 132Analysis of [3H]bremazocine binding in single and combinatorial opioid receptor knockout mice. Eur J Pharmacol. 2001 Mar 2;414(2-3):189-95.
REF 133[3H]U-69593 a highly selective ligand for the opioid kappa receptor. Eur J Pharmacol. 1985 Feb 26;109(2):281-4.
REF 134Potent and selective indolomorphinan antagonists of the kappa-opioid receptor. J Med Chem. 2000 Jul 13;43(14):2759-69.
REF 135Beta-endorphin is a potent inhibitor of thymidine incorporation into DNA via mu- and kappa-opioid receptors in fetal rat brain cell aggregates in culture. J Neurochem. 1993 Feb;60(2):765-7.
REF 136Pharmacological profiles of opioid ligands at kappa opioid receptors. BMC Pharmacol. 2006 Jan 25;6:3.
REF 137[6-O-methyl-11C]Diprenorphine, Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013. 2006 May 24 [updated 2007 May 12].
REF 138FK-506-binding protein: three-dimensional structure of the complex with the antagonist L-685,818. J Biol Chem. 1993 May 25;268(15):11335-9.
REF 139LY2456302 is a novel, potent, orally-bioavailable small molecule kappa-selective antagonist with activity in animal models predictive of efficacy in mood and addictive disorders. Neuropharmacology. 2014 Feb;77:131-44.
REF 140The 12 kD FK 506 binding protein FKBP12 is released in the male reproductive tract and stimulates sperm motility. Mol Med. 1998 Aug;4(8):502-14.
REF 141kappa-Opioid receptor in humans: cDNA and genomic cloning, chromosomal assignment, functional expression, pharmacology, and expression pattern in the central nervous system. Proc Natl Acad Sci U S A.1995 Jul 18;92(15):7006-10.
REF 142NMR studies of an FK-506 analog, [U-13C]ascomycin, bound to FK-506-binding protein. J Med Chem. 1992 Jun 26;35(13):2467-73.
REF 143Systemic effects of E-2078, a stabilized dynorphin A(1-8) analog, in rhesus monkeys. Psychopharmacology (Berl). 1999 Apr;143(2):190-6.
REF 144[(11)C]-GR89696, a potent kappa opiate receptor radioligand; in vivo binding of the R and S enantiomers. Nucl Med Biol. 2002 Jan;29(1):47-53.
REF 145GR94839, a kappa-opioid agonist with limited access to the central nervous system, has antinociceptive activity. Br J Pharmacol. 1992 Aug;106(4):783-9.
REF 146Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
REF 147Design and discovery of a selective small molecule ? opioid antagonist (2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242). J Med Chem. 2011 Aug 25;54(16):5868-77.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.