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
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
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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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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Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. | 2003 Mar |
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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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Identification of diverse microbial metabolites as potent inhibitors of HIV-1 Tat transactivation. | 2005 Jan |
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Serendipitous SAD phasing of an echinomycin-(ACGTACGT)2 bisintercalation complex. | 2006 Apr |
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Echinomycin and cobalt-phenanthroline as redox indicators of DNA hybridization at gold electrodes. | 2006 May 1 |
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Relative and absolute configuration of antitumor agent SW-163D. | 2007 Dec |
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Bisintercalator natural products with potential therapeutic applications: isolation, structure determination, synthetic and biological studies. | 2007 Feb |
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Dual effect of echinomycin on hypoxia-inducible factor-1 activity under normoxic and hypoxic conditions. | 2007 Nov |
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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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Indicator-based and indicator-free magnetic assays connected with disposable electrochemical nucleic acid sensor system. | 2009 Apr 15 |
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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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Signaling by hypoxia-inducible factors is critical for ovulation in mice. | 2009 Jul |
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Antitumor compounds from marine actinomycetes. | 2009 Jun 11 |
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TioS T-TE--a prototypical thioesterase responsible for cyclodimerization of the quinoline- and quinoxaline-type class of chromodepsipeptides. | 2009 Mar |
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Manganese (II) induces chemical hypoxia by inhibiting HIF-prolyl hydroxylase: implication in manganese-induced pulmonary inflammation. | 2009 Mar 15 |
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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 |
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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.
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Classification Tree | Code System | Code | ||
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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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ALTERNATIVE | |||
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ECHINOMYCIN
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DB15582
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512-64-1
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M4814
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PRIMARY | Merck Index | ||
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6857732
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ACTIVE MOIETY