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

Details

Stereochemistry UNKNOWN
Molecular Formula C51H64N12O12S2
Molecular Weight 1101.257
Optical Activity UNSPECIFIED
Defined Stereocenters 8 / 9
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ECHINOMYCIN

SMILES

CSC1SC[C@@H]2N(C)C(=O)[C@H](C)NC(=O)[C@@H](COC(=O)[C@H](C(C)C)N(C)C(=O)[C@H]1N(C)C(=O)[C@H](C)NC(=O)[C@@H](COC(=O)[C@H](C(C)C)N(C)C2=O)NC(=O)C3=NC4=C(C=CC=C4)N=C3)NC(=O)C5=NC6=C(C=CC=C6)N=C5

InChI

InChIKey=AUJXLBOHYWTPFV-VITLIGDRSA-N
InChI=1S/C51H64N12O12S2/c1-25(2)38-49(72)74-22-36(59-42(65)34-21-53-30-17-13-15-19-32(30)57-34)44(67)55-28(6)46(69)63(10)40-48(71)62(9)39(26(3)4)50(73)75-23-35(58-41(64)33-20-52-29-16-12-14-18-31(29)56-33)43(66)54-27(5)45(68)60(7)37(47(70)61(38)8)24-77-51(40)76-11/h12-21,25-28,35-40,51H,22-24H2,1-11H3,(H,54,66)(H,55,67)(H,58,64)(H,59,65)/t27-,28-,35+,36+,37-,38-,39-,40+,51?/m0/s1

HIDE SMILES / InChI

Molecular Formula C51H64N12O12S2
Molecular Weight 1101.257
Charge 0
Count
Stereochemistry EPIMERIC
Additional Stereochemistry No
Defined Stereocenters 8 / 9
E/Z Centers 0
Optical Activity UNSPECIFIED

Echinomycin is a cyclic peptide of the family of quinoxaline antibiotics that was originally isolated from Streptomyces echinatus. It is thought to act as a bifunctional DNA intercalator. Echinomycin has a binding site size of four base pairs. The strong binding sites for echinomycin contain the central two-base-pair sequence 5'-CG-3'. Echinomycin interferes with HIF-1 DNA binding in a sequence-specific fashion. It was brought into clinical trials by the NCI 20 years ago based on its antitumor activity. It has been extensively tested in phase I-II clinical trials. Nausea, vomiting, reversible liver enzyme abnormalities, and allergic reactions were the most common toxicities encountered. However, minimal or no antitumor activity was found in phase II clinical trials.

CNS Activity

Sources: DOI: 10.1007/s13273-017-0025-6
Curator's Comment: predicted

Originator

Sources: DOI: 10.1002/hlca.19570400124

Approval Year

Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
SW-163C and E, novel antitumor depsipeptides produced by Streptomyces sp. II. Structure elucidation.
2001 Aug
Total syntheses of thiocoraline and BE-22179 and assessment of their DNA binding and biological properties.
2001 Jan 31
Cyclic voltammetry of echinomycin and its interaction with double-stranded and single-stranded DNA adsorbed at the electrode.
2002 Jan
Validation of a sensitive assay for thiocoraline in mouse plasma using liquid chromatography-tandem mass spectrometry.
2003 Aug 25
Echinomycin and a novel analogue induce apoptosis of HT-29 cells via the activation of MAP kinases pathway.
2004 Aug
In vitro antibacterial activity of echinomycin and a novel analogue, YK2000, against vancomycin-resistant enterococci.
2004 Dec
Naturally occurring cyclohexane epoxides: sources, biological activities, and synthesis.
2004 Jun
Interaction of echinomycin with guanine: electrochemistry and spectroscopy studies.
2004 Nov 1
Structures of complexes between echinomycin and duplex DNA.
2005 Apr
Functional cross-talk between fatty acid synthesis and nonribosomal peptide synthesis in quinoxaline antibiotic-producing streptomycetes.
2005 Feb 11
Atomic force microscopy study of the structural effects induced by echinomycin binding to DNA.
2005 Jan 28
Echinomycin, a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity.
2005 Oct 1
Total biosynthesis of antitumor nonribosomal peptides in Escherichia coli.
2006 Aug
Molecular signaling cascade in DNA bisintercalator, echinomycin-induced apoptosis of HT-29 cells: evidence of the apoptotic process via activation of the cytochrome c-ERK-caspase-3 pathway.
2006 Feb
Identification and stereochemical assignment of the beta-hydroxytryptophan intermediate in the echinomycin biosynthetic pathway.
2006 Oct 12
Biochemistry. Directing biosynthesis.
2006 Oct 27
Modulating hypoxia-inducible transcription by disrupting the HIF-1-DNA interface.
2007 Aug 17
Bisintercalator natural products with potential therapeutic applications: isolation, structure determination, synthetic and biological studies.
2007 Feb
Robust platform for de novo production of heterologous polyketides and nonribosomal peptides in Escherichia coli.
2007 Feb 21
The short-term effects on restenosis and thrombosis of echinomycin-eluting stents topcoated with a hydrophobic heparin-containing polymer.
2007 Mar
Enzymatic macrolactonization in the presence of DNA leading to triostin A analogs.
2008 Aug 25
The effects of local DNA sequence on the interaction of ligands with their preferred binding sites.
2008 Jul
Complete sequence of biosynthetic gene cluster responsible for producing triostin A and evaluation of quinomycin-type antibiotics from Streptomyces triostinicus.
2008 Nov-Dec
Diversification of echinomycin molecular structure by way of chemoenzymatic synthesis and heterologous expression of the engineered echinomycin biosynthetic pathway.
2009 Apr
Gallium (III) triflate-catalyzed synthesis of heterocycles: quinoxalines, 1,5-benzodiazepines and their fluorinated derivatives.
2009 Aug
Interaction of an echinomycin-DNA complex with manganese ions.
2009 Jul 1
Escherichia coli allows efficient modular incorporation of newly isolated quinomycin biosynthetic enzyme into echinomycin biosynthetic pathway for rational design and synthesis of potent antibiotic unnatural natural product.
2009 Jul 8
Antitumor compounds from marine actinomycetes.
2009 Jun 11
A ferrocene-quinoxaline derivative as a highly selective probe for colorimetric and redox sensing of toxic mercury(II) cations.
2010
Pharmacological and genetic accumulation of hypoxia-inducible factor-1alpha enhances excitatory synaptic transmission in hippocampal neurons through the production of vascular endothelial growth factor.
2010 Apr 28
3-Methyl-1-(prop-2-en-1-yl)quinoxalin-2(1H)-one.
2010 Jun 23
Capture of a Transition State Using Molecular Dynamics: Creation of an Intercalation Site in dsDNA with Ethidium Cation.
2010 Mar 31
Patents

Sample Use Guides

1200 ug/m2 over 30-60 minutes once a week for 4 weeks, repeated every 6 weeks
Route of Administration: Intravenous
Echinomycin very potently inhibited hypoxic induction of luciferase expression in U251-HRE in a dose-dependent fashion with an EC50 of 1.2 nmol/L. U251-HRE cells were treated with Echinomycin at 5, 10, and 20 nmol/L for 4 hours and then washed and incubated under normoxic or hypoxic conditions for 36 hours. 94%, 80%, and 42% of hypoxiainduced luciferase expression was restored in cells in which Echinomycin was washed out after 4-hour treatment at 5, 10, and 20 nmol/L, respectively, indicating that the DNA-binding activity of Echinomycin is in fact reversible.
Substance Class Chemical
Created
by admin
on Sat Dec 17 23:11:57 UTC 2022
Edited
by admin
on Sat Dec 17 23:11:57 UTC 2022
Record UNII
TG824J6RQT
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ECHINOMYCIN
MI  
Common Name English
NSC-13502
Code English
LEVOMYCIN
Common Name English
N-(2-QUINOXALINYLCARBONYL)-O-(N-(2-QUINOXALINYLCARBONYL)-D-SERYL-L-ALANYL-3-MERCAPTO-N,S-DIMETHYLCYSTEINYL-N-METHYL-L-VALYL)-D-SERYL-L-ALANYL-N-METHYLCYSTEINYL-N-METHYL L-VALINE (8->1)-LACTONE CYCLIC (3->7)-THIOESTER
Systematic Name English
QUINOMYCIN A
Common Name English
NSC-526417
Code English
SK-302B
Code English
ECHINOMYCIN [MI]
Common Name English
ANTIBIOTIC A-654I
Code English
L-VALINE, N-(2-QUINOXALINYLCARBONYL)-O-(N-(2-QUINOXALINYLCARBONYL)-D-SERYL-L-ALANYL-3-MERCAPTO-N,S-DIMETHYLCYSTEINYL-N-METHYL-L-VALYL)-D-SERYL-L-ALANYL-N-METHYLCYSTEINYL-N-METHYL-, (8->1)-LACTONE, CYCLIC (3->7)-THIOETHER
Systematic Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 479815
Created by admin on Sat Dec 17 23:11:57 UTC 2022 , Edited by admin on Sat Dec 17 23:11:57 UTC 2022
FDA ORPHAN DRUG 549016
Created by admin on Sat Dec 17 23:11:57 UTC 2022 , Edited by admin on Sat Dec 17 23:11:57 UTC 2022
NCI_THESAURUS C582
Created by admin on Sat Dec 17 23:11:57 UTC 2022 , Edited by admin on Sat Dec 17 23:11:57 UTC 2022
Code System Code Type Description
CAS
512-64-1
Created by admin on Sat Dec 17 23:11:57 UTC 2022 , Edited by admin on Sat Dec 17 23:11:57 UTC 2022
PRIMARY
FDA UNII
TG824J6RQT
Created by admin on Sat Dec 17 23:11:57 UTC 2022 , Edited by admin on Sat Dec 17 23:11:57 UTC 2022
PRIMARY
MESH
D004448
Created by admin on Sat Dec 17 23:11:57 UTC 2022 , Edited by admin on Sat Dec 17 23:11:57 UTC 2022
PRIMARY
NCI_THESAURUS
C462
Created by admin on Sat Dec 17 23:11:57 UTC 2022 , Edited by admin on Sat Dec 17 23:11:57 UTC 2022
PRIMARY
CAS
1403-88-9
Created by admin on Sat Dec 17 23:11:57 UTC 2022 , Edited by admin on Sat Dec 17 23:11:57 UTC 2022
ALTERNATIVE
WIKIPEDIA
ECHINOMYCIN
Created by admin on Sat Dec 17 23:11:57 UTC 2022 , Edited by admin on Sat Dec 17 23:11:57 UTC 2022
PRIMARY
NSC
13502
Created by admin on Sat Dec 17 23:11:57 UTC 2022 , Edited by admin on Sat Dec 17 23:11:57 UTC 2022
PRIMARY
NSC
526417
Created by admin on Sat Dec 17 23:11:57 UTC 2022 , Edited by admin on Sat Dec 17 23:11:57 UTC 2022
PRIMARY
DRUG BANK
DB15582
Created by admin on Sat Dec 17 23:11:57 UTC 2022 , Edited by admin on Sat Dec 17 23:11:57 UTC 2022
PRIMARY
EPA CompTox
DTXSID5031266
Created by admin on Sat Dec 17 23:11:57 UTC 2022 , Edited by admin on Sat Dec 17 23:11:57 UTC 2022
PRIMARY
MERCK INDEX
M4814
Created by admin on Sat Dec 17 23:11:57 UTC 2022 , Edited by admin on Sat Dec 17 23:11:57 UTC 2022
PRIMARY Merck Index
PUBCHEM
6857732
Created by admin on Sat Dec 17 23:11:57 UTC 2022 , Edited by admin on Sat Dec 17 23:11:57 UTC 2022
PRIMARY
Related Record Type Details
ACTIVE MOIETY