DERMORPHIN

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 Search

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/3831962 | https://www.ncbi.nlm.nih.gov/pubmed/26756519

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.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Mu-type opioid receptor 61 Target ID: P35372\|\|\|G8XRH8\|\|\|Q5TDA1\|\|\|Q9UN57 Gene ID: 4988.0 Gene Symbol: OPRM1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26756519	Agonist 2678		8.8 null [pKi]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Postoperative pain 22 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3831962	Primary		Phase II 1132	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
20 ug single, intrathecal (unknown) Studied dose Dose: 20 ug Route: intrathecal Route: single Dose: 20 ug Sources: https://pubmed.ncbi.nlm.nih.gov/3831962	unhealthy n = 50 Health Status: unhealthy Condition: pain Sex: M+F Food Status: UNKNOWN Population Size: 50 Sources: https://pubmed.ncbi.nlm.nih.gov/3831962	Other AEs: Headache, Nausea... Other AEs: Headache (6%) Nausea (22%) vomiting (22%) Urinary retention (26%) Sources: https://pubmed.ncbi.nlm.nih.gov/3831962

AEs

AE	Significance	Dose	Population
Nausea	22%	20 ug single, intrathecal (unknown) Studied dose Dose: 20 ug Route: intrathecal Route: single Dose: 20 ug Sources: https://pubmed.ncbi.nlm.nih.gov/3831962	unhealthy n = 50 Health Status: unhealthy Condition: pain Sex: M+F Food Status: UNKNOWN Population Size: 50 Sources: https://pubmed.ncbi.nlm.nih.gov/3831962
vomiting	22%	20 ug single, intrathecal (unknown) Studied dose Dose: 20 ug Route: intrathecal Route: single Dose: 20 ug Sources: https://pubmed.ncbi.nlm.nih.gov/3831962	unhealthy n = 50 Health Status: unhealthy Condition: pain Sex: M+F Food Status: UNKNOWN Population Size: 50 Sources: https://pubmed.ncbi.nlm.nih.gov/3831962
Urinary retention	26%	20 ug single, intrathecal (unknown) Studied dose Dose: 20 ug Route: intrathecal Route: single Dose: 20 ug Sources: https://pubmed.ncbi.nlm.nih.gov/3831962	unhealthy n = 50 Health Status: unhealthy Condition: pain Sex: M+F Food Status: UNKNOWN Population Size: 50 Sources: https://pubmed.ncbi.nlm.nih.gov/3831962
Headache	6%	20 ug single, intrathecal (unknown) Studied dose Dose: 20 ug Route: intrathecal Route: single Dose: 20 ug Sources: https://pubmed.ncbi.nlm.nih.gov/3831962	unhealthy n = 50 Health Status: unhealthy Condition: pain Sex: M+F Food Status: UNKNOWN Population Size: 50 Sources: https://pubmed.ncbi.nlm.nih.gov/3831962

Sourcing

Vendor/Aggregator	ID	URL
AbovChem LLC	HY-P0244
Alfa Chemistry	232577	http://www.alfa-chemistry.com/search.aspx?q=232577
Alfa Chemistry	ACM77614165	http://www.alfa-chemistry.com/search.aspx?q=ACM77614165
BOC Sciences	77614-16-5	http://www.bocsci.com/description.asp?cas=77614-16-5
Bachem	H-2565	https://shop.bachem.com/catalogsearch/result/?q=H-2565
Chem Scene	CS-7103	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-7103
Compound Cloud	5485199
Hangzhou Yuhao Chemical Technology	RT5660
MedChem Express	HY-P0244	https://www.medchemexpress.com/search.html?q=HY-P0244&ft=&fa=&fp=
MolPort	MolPort-016-581-003	https://www.molport.com/shop/molecule-link/MolPort-016-581-003
MolPort	MolPort-046-689-305	https://www.molport.com/shop/molecule-link/MolPort-046-689-305
Toronto Research Chemicals	D281940	https://www.trc-canada.com/product-detail/?CatNum=D281940
Toronto Research Chemicals	M264630	https://www.trc-canada.com/product-detail/?CatNum=M264630
eMolecules	43477173	https://orderbb.emolecules.com/search/#?query=43477173
mcule	MCULE-3764930303	https://mcule.com/MCULE-3764930303/

PubMed

Title	Date	PubMed
Human brain cathepsin H as a neuropeptide and bradykinin metabolizing enzyme.	2003 Dec	15127951
Potent side-chain to side-chain cyclized dermorphin analogues containing a carbonyl bridge.	2003 Oct	14620130
Expression of EGFP-amino-tagged human mu opioid receptor in Drosophila Schneider 2 cells: a potential expression system for large-scale production of G-protein coupled receptors.	2003 Sep	12963349
Enhanced evoked excitatory transmitter release in experimental neuropathy requires descending facilitation.	2003 Sep 10	12967999
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	14518129
[Thermoregulatory activity of dermorphin fragments].	2004 Sep-Oct	15559135
Synthesis of dermorphin-(1-4) derivatives catalyzed by proteases in organic solvents.	2005 Jan	15686545
[Study of thermoregulatory activity of a fragment of natural dermorphin precursor Arg-dermorphin and its analogs].	2005 Jan-Feb	15768633
Distinguishing and quantifying peptides and proteins containing D-amino acids by tandem mass spectrometry.	2005 Jul 15	16013875
Abbreviated nomenclature for cyclic and branched homo- and hetero-detic peptides.	2005 Jun	15885114
[Analgesic activity of dermorphin and its proline analogs].	2005 Mar-Apr	15934358
6-Hydroxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid mimics active conformation of tyrosine in opioid peptides.	2005 May 16	15863298
[Comparative study of the physical dependence on proline analog of dermorphin and morphine].	2005 May-Jun	16047673
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	16218989
[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	16405030
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	15894374
Cyclic dermorphin tetrapeptide analogues obtained via ring-closing metathesis.	2006	16496038
Effects of the intravenous administration of [Lys7]dermorphin on local cerebral glucose utilization in the rat.	2006 Aug 21	16831415
Targeted drug delivery crossing cytoplasmic membranes of intended cells via ligand-grafted sterically stabilized liposomes.	2006 Feb 21	16356575
Involvement of spinal mu1-opioid receptors on the Tyr-d-Arg-Phe-sarcosine-induced antinociception.	2006 Jul 1	16730704
Descending facilitation from the rostral ventromedial medulla maintains nerve injury-induced central sensitization.	2006 Jul 21	16650614
Involvement of endogenous opioid peptides in the antinociception induced by the novel dermorphin tetrapeptide analog amidino-TAPA.	2007 Apr 10	17307162
Ureido group containing cyclic dermorphin(1-7) analogues: synthesis, biology and conformation.	2007 Aug	17605130
Receptor binding properties and antinociceptive effects of chimeric peptides consisting of a micro-opioid receptor agonist and an ORL1 receptor antagonist.	2007 Jul	17603164
Supranodose vagotomy eliminates respiratory depression evoked by dermorphin in anaesthetized rats.	2007 Jun 1	17362918
Novel glycosylated [Lys(7)]-dermorphin analogues: synthesis, biological activity and conformational investigations.	2007 Mar	17177323
[The relationship between the structure of dermorphines and their thermoregulatory activity].	2007 Nov-Dec	19768965
Dependence of the analgesic activities of dermorphin, metenkephalin, and dynorphin A on the ambient temperature.	2007 Nov-Dec	18274480
[Synthesis, pharmacokinetics, and metabolism of the C-terminal tripeptide of dermorphin and its diastereomer].	2007 Nov-Dec	18173119
Effect of sedatin (synthetic dermorphin analog) on the development of Acipenser schrenckii young fish.	2007 Oct	18642708
Effect of synthetic dermorphin analogues on tissue homeostasis in the myocardium of newborn albino rats.	2007 Oct	18642706
Mechanisms for the effect of arginine-containing dermorphin analogue on proliferative processes in the gastric mucosa of albino rats.	2007 Sep	18457022
[Comparative analysis of analgesic activities of dermorphin, [DPro6]-dermorphin, and their C-terminal tripeptides].	2007 Sep-Oct	18038625
Methylnaltrexone in the treatment of opioid-induced constipation.	2008	21677823
Multiple ligands in opioid research.	2008	18782061
Blood-brain barrier penetration by two dermorphin tetrapeptide analogues: role of lipophilicity vs structural flexibility.	2008 Apr 24	18370374
Conformation-activity relationships of cyclo-constrained micro/delta opioid agonists derived from the N-terminal tetrapeptide segment of dermorphin/deltorphin.	2008 Aug	18338322
Amygdala intercalated neurons are required for expression of fear extinction.	2008 Jul 31	18615014
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	18536274
Conformation-activity relationships of cyclo-constrained mu/delta opioid agonists derived from the N-terminal tetrapeptide segment of dermorphin/deltorphin.	2009	19400278
Discovery of dermorphin-based affinity labels with subnanomolar affinity for mu opioid receptors.	2009 Dec 10	19621878
[Significance of opioid receptors in regulation of cardiac tolerance in pathogenic impact of long-term ischemia-reperfusion in vivo].	2009 Jun	19639880
D-amino acid detection in peptides by MALDI-TOF-TOF.	2009 Jun 1	19476389
Neuropathic pain is maintained by brainstem neurons co-expressing opioid and cholecystokinin receptors.	2009 Mar	19050032
Evaluation of side effects through selective ablation of the mu opioid receptor expressing descending nociceptive facilitatory neurons in the rostral ventromedial medulla with dermorphin-saporin.	2009 Nov	19559047
Purification and functional reconstitution of monomeric mu-opioid receptors: allosteric modulation of agonist binding by Gi2.	2009 Sep 25	19542234
Partial ablation of mu-opioid receptor rich striosomes produces deficits on a motor-skill learning task.	2009 Sep 29	19463902
AntiBP2: improved version of antibacterial peptide prediction.	2010 Jan 18	20122190
Opioid receptor internalization contributes to dermorphin-mediated antinociception.	2010 Jun 30	20394808
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	21870874

Patents

Sample Use Guides

In Vivo Use Guide

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

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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