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
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
PubMed
| Title | Date | PubMed |
|---|---|---|
| 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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| Interaction of DNA with echinomycin at the mercury electrode surface as detected by impedance and chronopotentiometric measurements. | 2002 Apr 1 |
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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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| Interaction of Hoechst 33258 and echinomycin with nucleosomal DNA fragments containing isolated ligand binding sites. | 2002 Mar 12 |
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| 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 |
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| 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 |
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| Echinomycin and cobalt-phenanthroline as redox indicators of DNA hybridization at gold electrodes. | 2006 May 1 |
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| 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 |
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| Signaling by hypoxia-inducible factors is critical for ovulation in mice. | 2009 Jul |
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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 |
|
| 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.
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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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| Code System | Code | Type | Description | ||
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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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ACTIVE MOIETY
