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
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
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
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL4261 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16204079 |
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Target ID: CHEMBL5618 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16204079 |
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Target ID: CHEMBL2311221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6089341 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Sources: https://www.ncbi.nlm.nih.gov/pubmed/8617582 |
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
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SW-163C and E, novel antitumor depsipeptides produced by Streptomyces sp. II. Structure elucidation. | 2001 Aug |
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Total syntheses of thiocoraline and BE-22179 and assessment of their DNA binding and biological properties. | 2001 Jan 31 |
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Cyclic voltammetry of echinomycin and its interaction with double-stranded and single-stranded DNA adsorbed at the electrode. | 2002 Jan |
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Validation of a sensitive assay for thiocoraline in mouse plasma using liquid chromatography-tandem mass spectrometry. | 2003 Aug 25 |
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Echinomycin and a novel analogue induce apoptosis of HT-29 cells via the activation of MAP kinases pathway. | 2004 Aug |
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In vitro antibacterial activity of echinomycin and a novel analogue, YK2000, against vancomycin-resistant enterococci. | 2004 Dec |
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Naturally occurring cyclohexane epoxides: sources, biological activities, and synthesis. | 2004 Jun |
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Interaction of echinomycin with guanine: electrochemistry and spectroscopy studies. | 2004 Nov 1 |
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Structures of complexes between echinomycin and duplex DNA. | 2005 Apr |
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Functional cross-talk between fatty acid synthesis and nonribosomal peptide synthesis in quinoxaline antibiotic-producing streptomycetes. | 2005 Feb 11 |
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Atomic force microscopy study of the structural effects induced by echinomycin binding to DNA. | 2005 Jan 28 |
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Echinomycin, a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity. | 2005 Oct 1 |
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Total biosynthesis of antitumor nonribosomal peptides in Escherichia coli. | 2006 Aug |
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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 |
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Identification and stereochemical assignment of the beta-hydroxytryptophan intermediate in the echinomycin biosynthetic pathway. | 2006 Oct 12 |
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Biochemistry. Directing biosynthesis. | 2006 Oct 27 |
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Modulating hypoxia-inducible transcription by disrupting the HIF-1-DNA interface. | 2007 Aug 17 |
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Bisintercalator natural products with potential therapeutic applications: isolation, structure determination, synthetic and biological studies. | 2007 Feb |
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Robust platform for de novo production of heterologous polyketides and nonribosomal peptides in Escherichia coli. | 2007 Feb 21 |
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The short-term effects on restenosis and thrombosis of echinomycin-eluting stents topcoated with a hydrophobic heparin-containing polymer. | 2007 Mar |
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Enzymatic macrolactonization in the presence of DNA leading to triostin A analogs. | 2008 Aug 25 |
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The effects of local DNA sequence on the interaction of ligands with their preferred binding sites. | 2008 Jul |
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Complete sequence of biosynthetic gene cluster responsible for producing triostin A and evaluation of quinomycin-type antibiotics from Streptomyces triostinicus. | 2008 Nov-Dec |
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Diversification of echinomycin molecular structure by way of chemoenzymatic synthesis and heterologous expression of the engineered echinomycin biosynthetic pathway. | 2009 Apr |
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Gallium (III) triflate-catalyzed synthesis of heterocycles: quinoxalines, 1,5-benzodiazepines and their fluorinated derivatives. | 2009 Aug |
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Interaction of an echinomycin-DNA complex with manganese ions. | 2009 Jul 1 |
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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 |
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Antitumor compounds from marine actinomycetes. | 2009 Jun 11 |
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A ferrocene-quinoxaline derivative as a highly selective probe for colorimetric and redox sensing of toxic mercury(II) cations. | 2010 |
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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 |
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3-Methyl-1-(prop-2-en-1-yl)quinoxalin-2(1H)-one. | 2010 Jun 23 |
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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
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9445185
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16204079
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
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admin
on
Edited
Sat Dec 17 23:11:57 UTC 2022
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on
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Record UNII |
TG824J6RQT
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Record Status |
Validated (UNII)
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Record Version |
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FDA ORPHAN DRUG |
479815
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FDA ORPHAN DRUG |
549016
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NCI_THESAURUS |
C582
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512-64-1
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TG824J6RQT
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D004448
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C462
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1403-88-9
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ECHINOMYCIN
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13502
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526417
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DB15582
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DTXSID5031266
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M4814
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6857732
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