ECHINOMYCIN

Investigational

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 Search

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

Description
Sources: DOI: 10.1007/s13273-017-0025-6 | https://www.ncbi.nlm.nih.gov/pubmed/6089341 | https://www.ncbi.nlm.nih.gov/pubmed/16204079 | https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=39587

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Hypoxia-inducible factor 1 alpha 16 Target ID: CHEMBL4261 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16204079	Inhibitor 8146
Aryl hydrocarbon receptor nuclear translocator 1 Target ID: CHEMBL5618 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16204079	Inhibitor 8146
DNA 241 Target ID: CHEMBL2311221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6089341	Binding Agent 1037

Conditions

Condition	Modality	Highest Phase	Product
Non-small cell lung cancer 197 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9445185	Primary	Phase II 1133	Unknown Approved Use Unknown
Sarcoma 14 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8617582	Primary	Phase II 1133	Unknown Approved Use Unknown
Renal cell carcinoma 27 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7860234 https://www.ncbi.nlm.nih.gov/pubmed/8262733 http://adisinsight.springer.com/drugs/800004274	Primary	Phase II 1133	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
GLUT1 15	supressor 149 Sources: https://www.sciencedirect.com/science/article/pii/S2405844020308306	yes

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY557633	https://www.001chemical.com/chem/512-64-1
AA Blocks	AA00D7U8	https://www.aablocks.com/goods/Goods/detail?id=AA00D7U8
AK Scientific, Inc. (AKSCI)	2677AH	http://www.aksci.com/item_detail.php?cat=2677AH
Alfa Chemistry	AP512641	https://reagents.alfa-chemistry.com/product/echinomycin-cas-512-64-1-12287.html
Ambinter	Amb16182781	http://www.ambinter.com/reference/16182781
Ambinter	Amb19930583	http://www.ambinter.com/reference/19930583
Ambinter	Amb22352704	http://www.ambinter.com/reference/22352704
Aurora Fine Chemicals LLC	A24.087.937	http://online.aurorafinechemicals.com/info?ID=A24.087.937
AvaChem Scientific	6302	https://www.avachem.com/productSearch.asp?6302
BOC Sciences	512-64-1	https://www.bocsci.com/quinomycin-a-cas-512-64-1-item-120819.html
BioChemPartner	BCP23887	http://www.biochempartner.com/512-64-1-BCP23887
Chem Scene	CS-0024860	http://www.chemscene.com/512-64-1.html
ChemMol	99097812	http://www.chemmol.com/chemmol/99097812.html
DC Chemicals	DC32277	http://www.dcchemicals.com//product_show-Echinomycin.html
Glentham Life Sciences	GA8422	http://www.glentham.com/products/product/GA8422/
Hello Bio	HB3882	https://www.hellobio.com/echinosporin.html
Lab Network	LN01319202	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01319202
MedChem Express	HY-106101	https://www.medchemexpress.com/echinomycin.html
MolPort	MolPort-003-933-120	https://www.molport.com/shop/molecule-link/MolPort-003-933-120
MolPort	MolPort-019-939-218	https://www.molport.com/shop/molecule-link/MolPort-019-939-218
MolPort	MolPort-046-162-822	https://www.molport.com/shop/molecule-link/MolPort-046-162-822
Molcore	MC557633	https://www.molcore.com/product/512-64-1
Nextpeptide	NP182327	http://www.nextpeptide.com/512-64-1.html
Smolecule	S526852	http://www.smolecule.com/products/s526852
Smolecule	S532977	http://www.smolecule.com/products/s532977
Smolecule	S701871	https://www.smolecule.com/products/s701871
THE BioTek	bt-267032	https://www.thebiotek.com/product/inhibitors/bt-267032
THE BioTek	bt-272650	https://www.thebiotek.com/product/inhibitors/bt-272650
Tocris	5520	https://www.tocris.com/products/echinomycin_5520
abcr GmbH	AB259479	http://www.abcr.com/shop/en/AB259479
eNovation Chemicals	D670246	https://www.enovationchem.com/ProductDetails.asp?ProductID=D670246
iChemical	EBD541059	http://www.ichemical.com/products/512-64-1.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
SW-163C and E, novel antitumor depsipeptides produced by Streptomyces sp. II. Structure elucidation.	2001 Aug	11592498
Total syntheses of thiocoraline and BE-22179 and assessment of their DNA binding and biological properties.	2001 Jan 31	11456568
Cyclic voltammetry of echinomycin and its interaction with double-stranded and single-stranded DNA adsorbed at the electrode.	2002 Jan	11786366
Validation of a sensitive assay for thiocoraline in mouse plasma using liquid chromatography-tandem mass spectrometry.	2003 Aug 25	12888201
Echinomycin and a novel analogue induce apoptosis of HT-29 cells via the activation of MAP kinases pathway.	2004 Aug	15177310
In vitro antibacterial activity of echinomycin and a novel analogue, YK2000, against vancomycin-resistant enterococci.	2004 Dec	15555887
Naturally occurring cyclohexane epoxides: sources, biological activities, and synthesis.	2004 Jun	15186183
Interaction of echinomycin with guanine: electrochemistry and spectroscopy studies.	2004 Nov 1	15501569
Structures of complexes between echinomycin and duplex DNA.	2005 Apr	15805599
Functional cross-talk between fatty acid synthesis and nonribosomal peptide synthesis in quinoxaline antibiotic-producing streptomycetes.	2005 Feb 11	15569690
Atomic force microscopy study of the structural effects induced by echinomycin binding to DNA.	2005 Jan 28	15588823
Echinomycin, a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity.	2005 Oct 1	16204079
Total biosynthesis of antitumor nonribosomal peptides in Escherichia coli.	2006 Aug	16799553
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	16214385
Identification and stereochemical assignment of the beta-hydroxytryptophan intermediate in the echinomycin biosynthetic pathway.	2006 Oct 12	17020286
Biochemistry. Directing biosynthesis.	2006 Oct 27	17068249
Modulating hypoxia-inducible transcription by disrupting the HIF-1-DNA interface.	2007 Aug 17	17708671
Bisintercalator natural products with potential therapeutic applications: isolation, structure determination, synthetic and biological studies.	2007 Feb	17268609
Robust platform for de novo production of heterologous polyketides and nonribosomal peptides in Escherichia coli.	2007 Feb 21	17285165
The short-term effects on restenosis and thrombosis of echinomycin-eluting stents topcoated with a hydrophobic heparin-containing polymer.	2007 Mar	17157376
Enzymatic macrolactonization in the presence of DNA leading to triostin A analogs.	2008 Aug 25	18721753
The effects of local DNA sequence on the interaction of ligands with their preferred binding sites.	2008 Jul	18226601
Complete sequence of biosynthetic gene cluster responsible for producing triostin A and evaluation of quinomycin-type antibiotics from Streptomyces triostinicus.	2008 Nov-Dec	19194935
Diversification of echinomycin molecular structure by way of chemoenzymatic synthesis and heterologous expression of the engineered echinomycin biosynthetic pathway.	2009 Apr	19278894
Gallium (III) triflate-catalyzed synthesis of heterocycles: quinoxalines, 1,5-benzodiazepines and their fluorinated derivatives.	2009 Aug	21426089
Interaction of an echinomycin-DNA complex with manganese ions.	2009 Jul 1	19574634
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	19514719
Antitumor compounds from marine actinomycetes.	2009 Jun 11	19597582
A ferrocene-quinoxaline derivative as a highly selective probe for colorimetric and redox sensing of toxic mercury(II) cations.	2010	22163528
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	20427666
3-Methyl-1-(prop-2-en-1-yl)quinoxalin-2(1H)-one.	2010 Jun 23	21587981
Capture of a Transition State Using Molecular Dynamics: Creation of an Intercalation Site in dsDNA with Ethidium Cation.	2010 Mar 31	20798766

Patents

Sample Use Guides

In Vivo Use Guide

1200 ug/m2 over 30-60 minutes once a week for 4 weeks, repeated every 6 weeks

Route of Administration: Intravenous

In Vitro Use Guide

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

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