U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C40H50N8O10
Molecular Weight 802.8726
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DERMORPHIN

SMILES

C[C@@H](NC(=O)[C@@H](N)CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)NCC(=O)N[C@@H](CC3=CC=C(O)C=C3)C(=O)N4CCC[C@H]4C(=O)N[C@@H](CO)C(N)=O

InChI

InChIKey=FHZPGIUBXYVUOY-VWGYHWLBSA-N
InChI=1S/C40H50N8O10/c1-23(44-37(55)29(41)18-25-9-13-27(50)14-10-25)36(54)46-30(19-24-6-3-2-4-7-24)38(56)43-21-34(52)45-31(20-26-11-15-28(51)16-12-26)40(58)48-17-5-8-33(48)39(57)47-32(22-49)35(42)53/h2-4,6-7,9-16,23,29-33,49-51H,5,8,17-22,41H2,1H3,(H2,42,53)(H,43,56)(H,44,55)(H,45,52)(H,46,54)(H,47,57)/t23-,29+,30+,31+,32+,33+/m1/s1

HIDE SMILES / InChI

Molecular Formula C40H50N8O10
Molecular Weight 802.8726
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 6 / 6
E/Z Centers 0
Optical Activity UNSPECIFIED

Dermorphin is a selective mu-opioid receptor agonist. It was isolated from isolated from skin extracts of frogs belonging to the genus Phyllomedusa and was shown to relife pain in patients with postoperative pain syndrome.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P35372|||G8XRH8|||Q5TDA1|||Q9UN57
Gene ID: 4988.0
Gene Symbol: OPRM1
Target Organism: Homo sapiens (Human)
8.8 null [pKi]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
20 ug single, intrathecal (unknown)
Studied dose
Dose: 20 ug
Route: intrathecal
Route: single
Dose: 20 ug
Sources:
unhealthy
n = 50
Health Status: unhealthy
Condition: pain
Sex: M+F
Food Status: UNKNOWN
Population Size: 50
Sources:
Other AEs: Headache, Nausea...
Other AEs:
Headache (6%)
Nausea (22%)
vomiting (22%)
Urinary retention (26%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Nausea 22%
20 ug single, intrathecal (unknown)
Studied dose
Dose: 20 ug
Route: intrathecal
Route: single
Dose: 20 ug
Sources:
unhealthy
n = 50
Health Status: unhealthy
Condition: pain
Sex: M+F
Food Status: UNKNOWN
Population Size: 50
Sources:
vomiting 22%
20 ug single, intrathecal (unknown)
Studied dose
Dose: 20 ug
Route: intrathecal
Route: single
Dose: 20 ug
Sources:
unhealthy
n = 50
Health Status: unhealthy
Condition: pain
Sex: M+F
Food Status: UNKNOWN
Population Size: 50
Sources:
Urinary retention 26%
20 ug single, intrathecal (unknown)
Studied dose
Dose: 20 ug
Route: intrathecal
Route: single
Dose: 20 ug
Sources:
unhealthy
n = 50
Health Status: unhealthy
Condition: pain
Sex: M+F
Food Status: UNKNOWN
Population Size: 50
Sources:
Headache 6%
20 ug single, intrathecal (unknown)
Studied dose
Dose: 20 ug
Route: intrathecal
Route: single
Dose: 20 ug
Sources:
unhealthy
n = 50
Health Status: unhealthy
Condition: pain
Sex: M+F
Food Status: UNKNOWN
Population Size: 50
Sources:
PubMed

PubMed

TitleDatePubMed
Human brain cathepsin H as a neuropeptide and bradykinin metabolizing enzyme.
2003 Dec
Enhanced spontaneous activity of the mu opioid receptor by cysteine mutations: characterization of a tool for inverse agonist screening.
2003 Dec 1
Potent side-chain to side-chain cyclized dermorphin analogues containing a carbonyl bridge.
2003 Oct
Synthesis, conformation and biological activity of dermorphin and deltorphin I analogues containing N-alkylglycine in place of residues in position 1, 3, 5 and 6.
2003 Oct
Opioid peptides: synthesis and biological properties of [(N gamma-glucosyl,N gamma-methoxy)-alpha, gamma-diamino-(S)-butanoyl]4-deltorphin-1-neoglycopeptide and related analogues.
2003 Sep 7
Tolerance develops in spinal cord, but not in brain with chronic [Dmt1]DALDA treatment.
2004 Dec
Blood-brain barrier permeability of novel [D-arg2]dermorphin (1-4) analogs: transport property is related to the slow onset of antinociceptive activity in the central nervous system.
2004 Jul
[Thermoregulatory activity of dermorphin fragments].
2004 Sep-Oct
Synthesis of dermorphin-(1-4) derivatives catalyzed by proteases in organic solvents.
2005 Jan
New tris-alkoxycarbonyl arginine derivatives for peptide synthesis.
2005 Jan
[Study of thermoregulatory activity of a fragment of natural dermorphin precursor Arg-dermorphin and its analogs].
2005 Jan-Feb
Distinguishing and quantifying peptides and proteins containing D-amino acids by tandem mass spectrometry.
2005 Jul 15
Abbreviated nomenclature for cyclic and branched homo- and hetero-detic peptides.
2005 Jun
Cyclic enkephalin and dermorphin analogues containing a carbonyl bridge.
2005 Jun
[Analgesic activity of dermorphin and its proline analogs].
2005 Mar-Apr
6-Hydroxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid mimics active conformation of tyrosine in opioid peptides.
2005 May 16
[Comparative study of the physical dependence on proline analog of dermorphin and morphine].
2005 May-Jun
Synthesis and biological evaluation of constrained analogues of the opioid peptide H-Tyr-D-Ala-Phe-Gly-NH2 using the 4-amino-2-benzazepin-3-one scaffold.
2005 Nov
[Comparative study of the antiarrhythmic activity of mu- and delta-opioid receptor agonists during acute cardiac ischemia and reperfusion models in rats].
2005 Nov-Dec
Inhibitory control of the acute mu-withdrawal response by indirectly activated adenosine A1 and kappa-opioid systems in the Guinea-pig ileum; reversal by cholecystokinin.
2005 Oct
Cyclic dermorphin tetrapeptide analogues obtained via ring-closing metathesis.
2006
Effects of the intravenous administration of [Lys7]dermorphin on local cerebral glucose utilization in the rat.
2006 Aug 21
Targeted drug delivery crossing cytoplasmic membranes of intended cells via ligand-grafted sterically stabilized liposomes.
2006 Feb 21
Involvement of spinal mu1-opioid receptors on the Tyr-d-Arg-Phe-sarcosine-induced antinociception.
2006 Jul 1
Descending facilitation from the rostral ventromedial medulla maintains nerve injury-induced central sensitization.
2006 Jul 21
Involvement of endogenous opioid peptides in the antinociception induced by the novel dermorphin tetrapeptide analog amidino-TAPA.
2007 Apr 10
Ureido group containing cyclic dermorphin(1-7) analogues: synthesis, biology and conformation.
2007 Aug
Receptor binding properties and antinociceptive effects of chimeric peptides consisting of a micro-opioid receptor agonist and an ORL1 receptor antagonist.
2007 Jul
Supranodose vagotomy eliminates respiratory depression evoked by dermorphin in anaesthetized rats.
2007 Jun 1
Novel glycosylated [Lys(7)]-dermorphin analogues: synthesis, biological activity and conformational investigations.
2007 Mar
[The relationship between the structure of dermorphines and their thermoregulatory activity].
2007 Nov-Dec
Dependence of the analgesic activities of dermorphin, metenkephalin, and dynorphin A on the ambient temperature.
2007 Nov-Dec
[Synthesis, pharmacokinetics, and metabolism of the C-terminal tripeptide of dermorphin and its diastereomer].
2007 Nov-Dec
Effect of sedatin (synthetic dermorphin analog) on the development of Acipenser schrenckii young fish.
2007 Oct
Effect of synthetic dermorphin analogues on tissue homeostasis in the myocardium of newborn albino rats.
2007 Oct
Mechanisms for the effect of arginine-containing dermorphin analogue on proliferative processes in the gastric mucosa of albino rats.
2007 Sep
[Comparative analysis of analgesic activities of dermorphin, [DPro6]-dermorphin, and their C-terminal tripeptides].
2007 Sep-Oct
Methylnaltrexone in the treatment of opioid-induced constipation.
2008
Multiple ligands in opioid research.
2008
Blood-brain barrier penetration by two dermorphin tetrapeptide analogues: role of lipophilicity vs structural flexibility.
2008 Apr 24
Conformation-activity relationships of cyclo-constrained micro/delta opioid agonists derived from the N-terminal tetrapeptide segment of dermorphin/deltorphin.
2008 Aug
Amygdala intercalated neurons are required for expression of fear extinction.
2008 Jul 31
The use of tritium-labeled dermorphin for studying the interactions of C-terminal dermorphin fragment Tyr-Pro-Ser-NH2 and its stereoisomer Tyr-D-Pro-Ser-NH2 with opioid receptors.
2008 Mar-Apr
Conformation-activity relationships of cyclo-constrained mu/delta opioid agonists derived from the N-terminal tetrapeptide segment of dermorphin/deltorphin.
2009
Neuropathic pain is maintained by brainstem neurons co-expressing opioid and cholecystokinin receptors.
2009 Mar
Purification and functional reconstitution of monomeric mu-opioid receptors: allosteric modulation of agonist binding by Gi2.
2009 Sep 25
Partial ablation of mu-opioid receptor rich striosomes produces deficits on a motor-skill learning task.
2009 Sep 29
AntiBP2: improved version of antibacterial peptide prediction.
2010 Jan 18
Opioid receptor internalization contributes to dermorphin-mediated antinociception.
2010 Jun 30
Synthesis, biological evaluation, and automated docking of constrained analogues of the opioid peptide H-Dmt-D-Ala-Phe-Gly-NH₂ using the 4- or 5-methyl substituted 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one scaffold.
2011 Oct 13
Patents

Patents

Sample Use Guides

In a clinical trial, dermorphin was given at a dose of 20 uM intrathecally.
Route of Administration: Other
In Vitro Use Guide
Rat neurons were treated with dermorphin. The drug caused the inhibition of spontaneous firing of all neurons of the locus coeruleus tested, with an IC50 of 7 nM. Larger concentrations of dermorphin (30-100 nM) further hyperpolarized the neurons of the locus coeruleus and simultaneously caused a reduction in input resistance. These effects were antagonized by naloxone, with a dissociation equilibrium constant of 0.8 nM.
Substance Class Chemical
Created
by admin
on Sat Dec 16 04:51:19 GMT 2023
Edited
by admin
on Sat Dec 16 04:51:19 GMT 2023
Record UNII
2SEC01B703
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DERMORPHIN
Common Name English
TYR-D-ALA-PHE-GLY-TYR-PRO-SER-NH2
Common Name English
L-SERINAMIDE, L-TYROSYL-D-ALANYL-L-PHENYLALANYLGLYCYL-L-TYROSYL-L-PROLYL-
Common Name English
Code System Code Type Description
CAS
77614-16-5
Created by admin on Sat Dec 16 04:51:19 GMT 2023 , Edited by admin on Sat Dec 16 04:51:19 GMT 2023
PRIMARY
WIKIPEDIA
DERMORPHIN
Created by admin on Sat Dec 16 04:51:19 GMT 2023 , Edited by admin on Sat Dec 16 04:51:19 GMT 2023
PRIMARY
FDA UNII
2SEC01B703
Created by admin on Sat Dec 16 04:51:19 GMT 2023 , Edited by admin on Sat Dec 16 04:51:19 GMT 2023
PRIMARY
EPA CompTox
DTXSID40228281
Created by admin on Sat Dec 16 04:51:19 GMT 2023 , Edited by admin on Sat Dec 16 04:51:19 GMT 2023
PRIMARY
MESH
C030058
Created by admin on Sat Dec 16 04:51:19 GMT 2023 , Edited by admin on Sat Dec 16 04:51:19 GMT 2023
PRIMARY
PUBCHEM
5485199
Created by admin on Sat Dec 16 04:51:19 GMT 2023 , Edited by admin on Sat Dec 16 04:51:19 GMT 2023
PRIMARY
Related Record Type Details
OFF TARGET->NON-INHIBITOR
TARGET->WEAK AGONIST
TARGET -> AGONIST
Ki
TARGET -> AGONIST
IC50
Related Record Type Details
ACTIVE MOIETY