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Details

Stereochemistry UNKNOWN
Molecular Formula C51H64N12O12S2
Molecular Weight 1101.2612
Optical Activity UNSPECIFIED
Defined Stereocenters 8 / 9
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ECHINOMYCIN

SMILES

CC(C)[C@@]1([H])C(=O)OC[C@]([H])(C(=N[C@@]([H])(C)C(=O)N(C)[C@]2([H])C(=O)N(C)[C@@]([H])(C(C)C)C(=O)OC[C@]([H])(C(=N[C@@]([H])(C)C(=O)N(C)[C@@]([H])(CSC2([H])SC)C(=O)N1C)O)N=C(c3cnc4ccccc4n3)O)O)N=C(c5cnc6ccccc6n5)O

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 1101.2612
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
Interaction of DNA with echinomycin at the mercury electrode surface as detected by impedance and chronopotentiometric measurements.
2002 Apr 1
Identification of diverse microbial metabolites as potent inhibitors of HIV-1 Tat transactivation.
2005 Jan
[Echinomycin production by Actinomadura sp. INA 654].
2006
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
Identification and stereochemical assignment of the beta-hydroxytryptophan intermediate in the echinomycin biosynthetic pathway.
2006 Oct 12
Biochemistry. Directing biosynthesis.
2006 Oct 27
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
The short-term effects on restenosis and thrombosis of echinomycin-eluting stents topcoated with a hydrophobic heparin-containing polymer.
2007 Mar
Dual effect of echinomycin on hypoxia-inducible factor-1 activity under normoxic and hypoxic conditions.
2007 Nov
[Biosynthesis of natural products from microbes].
2007 Oct
Enzymatic macrolactonization in the presence of DNA leading to triostin A analogs.
2008 Aug 25
A dialogue between the hypoxia-inducible factor and the tumor microenvironment.
2008 Dec
In vitro and in vivo activities of echinomycin against clinical isolates of Staphylococcus aureus.
2008 Jan
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
[Recent progress in the study on antitumor drugs targeting hypoxia-inducible factor-1].
2008 Jun
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
Exploring the biosynthesis of natural products and their inherent suitability for the rational design of desirable compounds through genetic engineering.
2008 Oct
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
Indicator-based and indicator-free magnetic assays connected with disposable electrochemical nucleic acid sensor system.
2009 Apr 15
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
Control of oocyte release by progesterone receptor-regulated gene expression.
2009 Dec 31
Hypoxia decreases insulin signaling pathways in adipocytes.
2009 Jan
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
Automated genome mining for natural products.
2009 Jun 16
TioS T-TE--a prototypical thioesterase responsible for cyclodimerization of the quinoline- and quinoxaline-type class of chromodepsipeptides.
2009 Mar
Structure-activity studies of echinomycin antibiotics against drug-resistant and biofilm-forming Staphylococcus aureus and Enterococcus faecalis.
2009 Mar 1
Manganese (II) induces chemical hypoxia by inhibiting HIF-prolyl hydroxylase: implication in manganese-induced pulmonary inflammation.
2009 Mar 15
Recepteur d'origine nantais tyrosine kinase is a direct target of hypoxia-inducible factor-1alpha-mediated invasion of breast carcinoma cells.
2009 May 22
Evaluation of molecular descriptors for antitumor drugs with respect to noncovalent binding to DNA and antiproliferative activity.
2009 Sep 16
A ferrocene-quinoxaline derivative as a highly selective probe for colorimetric and redox sensing of toxic mercury(II) cations.
2010
Drug release from a chemically-anchored PEG/phospholipid monolayer onto polymer-coated metallic stents.
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
Insulin induces REDD1 expression through hypoxia-inducible factor 1 activation in adipocytes.
2010 Feb 19
Identification of cyclooxygenase-2 as a major actor of the transcriptomic adaptation of endothelial and tumor cells to cyclic hypoxia: effect on angiogenesis and metastases.
2010 Jan 15
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
Recent developments in bisintercalator natural products.
2010 Sep
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 Jun 26 16:06:39 UTC 2021
Edited
by admin
on Sat Jun 26 16:06:39 UTC 2021
Record UNII
TG824J6RQT
Record Status Validated (UNII)
Record Version
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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 Jun 26 16:06:39 UTC 2021 , Edited by admin on Sat Jun 26 16:06:39 UTC 2021
FDA ORPHAN DRUG 549016
Created by admin on Sat Jun 26 16:06:39 UTC 2021 , Edited by admin on Sat Jun 26 16:06:39 UTC 2021
NCI_THESAURUS C582
Created by admin on Sat Jun 26 16:06:39 UTC 2021 , Edited by admin on Sat Jun 26 16:06:39 UTC 2021
Code System Code Type Description
CAS
512-64-1
Created by admin on Sat Jun 26 16:06:39 UTC 2021 , Edited by admin on Sat Jun 26 16:06:39 UTC 2021
PRIMARY
FDA UNII
TG824J6RQT
Created by admin on Sat Jun 26 16:06:39 UTC 2021 , Edited by admin on Sat Jun 26 16:06:39 UTC 2021
PRIMARY
MESH
D004448
Created by admin on Sat Jun 26 16:06:39 UTC 2021 , Edited by admin on Sat Jun 26 16:06:39 UTC 2021
PRIMARY
NCI_THESAURUS
C462
Created by admin on Sat Jun 26 16:06:39 UTC 2021 , Edited by admin on Sat Jun 26 16:06:39 UTC 2021
PRIMARY
CAS
1403-88-9
Created by admin on Sat Jun 26 16:06:39 UTC 2021 , Edited by admin on Sat Jun 26 16:06:39 UTC 2021
ALTERNATIVE
WIKIPEDIA
ECHINOMYCIN
Created by admin on Sat Jun 26 16:06:39 UTC 2021 , Edited by admin on Sat Jun 26 16:06:39 UTC 2021
PRIMARY
DRUG BANK
DB15582
Created by admin on Sat Jun 26 16:06:39 UTC 2021 , Edited by admin on Sat Jun 26 16:06:39 UTC 2021
PRIMARY
EPA CompTox
512-64-1
Created by admin on Sat Jun 26 16:06:39 UTC 2021 , Edited by admin on Sat Jun 26 16:06:39 UTC 2021
PRIMARY
MERCK INDEX
M4814
Created by admin on Sat Jun 26 16:06:39 UTC 2021 , Edited by admin on Sat Jun 26 16:06:39 UTC 2021
PRIMARY Merck Index
PUBCHEM
6857732
Created by admin on Sat Jun 26 16:06:39 UTC 2021 , Edited by admin on Sat Jun 26 16:06:39 UTC 2021
PRIMARY
Related Record Type Details
ACTIVE MOIETY