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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
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
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
Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells.
2003 Mar
Echinomycin and a novel analogue induce apoptosis of HT-29 cells via the activation of MAP kinases pathway.
2004 Aug
Functional cross-talk between fatty acid synthesis and nonribosomal peptide synthesis in quinoxaline antibiotic-producing streptomycetes.
2005 Feb 11
Identification of diverse microbial metabolites as potent inhibitors of HIV-1 Tat transactivation.
2005 Jan
Serendipitous SAD phasing of an echinomycin-(ACGTACGT)2 bisintercalation complex.
2006 Apr
Echinomycin and cobalt-phenanthroline as redox indicators of DNA hybridization at gold electrodes.
2006 May 1
Relative and absolute configuration of antitumor agent SW-163D.
2007 Dec
Bisintercalator natural products with potential therapeutic applications: isolation, structure determination, synthetic and biological studies.
2007 Feb
Dual effect of echinomycin on hypoxia-inducible factor-1 activity under normoxic and hypoxic conditions.
2007 Nov
The effects of local DNA sequence on the interaction of ligands with their preferred binding sites.
2008 Jul
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
Signaling by hypoxia-inducible factors is critical for ovulation in mice.
2009 Jul
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
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
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.
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