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 |
|---|---|---|
| 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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| Echinomycin and a novel analogue induce apoptosis of HT-29 cells via the activation of MAP kinases pathway. | 2004 Aug |
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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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| Echinomycin, a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity. | 2005 Oct 1 |
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| Serendipitous SAD phasing of an echinomycin-(ACGTACGT)2 bisintercalation complex. | 2006 Apr |
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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 |
|
| 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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| Robust platform for de novo production of heterologous polyketides and nonribosomal peptides in Escherichia coli. | 2007 Feb 21 |
|
| 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 |
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| Enzymatic macrolactonization in the presence of DNA leading to triostin A analogs. | 2008 Aug 25 |
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| A dialogue between the hypoxia-inducible factor and the tumor microenvironment. | 2008 Dec |
|
| [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 |
|
| 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 |
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| Rationally engineered total biosynthesis of a synthetic analogue of a natural quinomycin depsipeptide in Escherichia coli. | 2009 Aug 17 |
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| Control of oocyte release by progesterone receptor-regulated gene expression. | 2009 Dec 31 |
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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 |
|
| Recepteur d'origine nantais tyrosine kinase is a direct target of hypoxia-inducible factor-1alpha-mediated invasion of breast carcinoma cells. | 2009 May 22 |
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| Evaluation of molecular descriptors for antitumor drugs with respect to noncovalent binding to DNA and antiproliferative activity. | 2009 Sep 16 |
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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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| Drug release from a chemically-anchored PEG/phospholipid monolayer onto polymer-coated metallic stents. | 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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| Insulin induces REDD1 expression through hypoxia-inducible factor 1 activation in adipocytes. | 2010 Feb 19 |
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| 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.
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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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100000178234
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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
