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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
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
Interaction of DNA with echinomycin at the mercury electrode surface as detected by impedance and chronopotentiometric measurements.
2002 Apr 1
Cyclic voltammetry of echinomycin and its interaction with double-stranded and single-stranded DNA adsorbed at the electrode.
2002 Jan
Interaction of Hoechst 33258 and echinomycin with nucleosomal DNA fragments containing isolated ligand binding sites.
2002 Mar 12
Validation of a sensitive assay for thiocoraline in mouse plasma using liquid chromatography-tandem mass spectrometry.
2003 Aug 25
Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells.
2003 Mar
Naturally occurring cyclohexane epoxides: sources, biological activities, and synthesis.
2004 Jun
Identification of diverse microbial metabolites as potent inhibitors of HIV-1 Tat transactivation.
2005 Jan
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
Serendipitous SAD phasing of an echinomycin-(ACGTACGT)2 bisintercalation complex.
2006 Apr
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
Synergistic effects of CoCl(2) and ROCK inhibition on mesenchymal stem cell differentiation into neuron-like cells.
2006 Jul 1
Echinomycin and cobalt-phenanthroline as redox indicators of DNA hybridization at gold electrodes.
2006 May 1
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
Probing ligand binding to duplex DNA using KMnO4 reactions and electrospray ionization tandem mass spectrometry.
2007 Jun 15
[Biosynthesis of natural products from microbes].
2007 Oct
Improved production of triostin A in engineered Escherichia coli with furnished quinoxaline chromophore by design of experiments in small-scale culture.
2008 Jan-Feb
The effects of local DNA sequence on the interaction of ligands with their preferred binding sites.
2008 Jul
Selective and potent in vitro antitrypanosomal activities of ten microbial metabolites.
2008 Jun
Complete sequence of biosynthetic gene cluster responsible for producing triostin A and evaluation of quinomycin-type antibiotics from Streptomyces triostinicus.
2008 Nov-Dec
NF-kappaB-dependency and consequent regulation of IL-8 in echinomycin-induced apoptosis of HT-29 colon cancer cells.
2008 Oct
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
Inhibition of hypoxia-inducible factor-1 function enhances the sensitivity of multiple myeloma cells to melphalan.
2009 Aug
Rationally engineered total biosynthesis of a synthetic analogue of a natural quinomycin depsipeptide in Escherichia coli.
2009 Aug 17
Signaling by hypoxia-inducible factors is critical for ovulation in mice.
2009 Jul
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
TioS T-TE--a prototypical thioesterase responsible for cyclodimerization of the quinoline- and quinoxaline-type class of chromodepsipeptides.
2009 Mar
Manganese (II) induces chemical hypoxia by inhibiting HIF-prolyl hydroxylase: implication in manganese-induced pulmonary inflammation.
2009 Mar 15
A ferrocene-quinoxaline derivative as a highly selective probe for colorimetric and redox sensing of toxic mercury(II) cations.
2010
3-Methyl-1-(prop-2-en-1-yl)quinoxalin-2(1H)-one.
2010 Jun 23
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.
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