Echinomycin
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| Category | Antineoplastic |
| Catalog number | BBF-01779 |
| CAS | 512-64-1 |
| Molecular Weight | 1101.25 |
| Molecular Formula | C51H64N12O12S2 |
| Purity | >99% by HPLC |
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Description
It is produced by the strain of Streptomyces echinatus. It has the activity of anti-gram-positive bacteria and vaginal trichomonas, and also has the effect on influenza virus and sarcoma 180 cells in vitro.
Specification
| Synonyms | Quinomycin A; Levomycin; N,N'-((1R,4S,7R,11S,14R,17S,20R,24S)-11,24-diisopropyl-2,4,12,15,17,25-hexamethyl-27-(methylthio)-3,6,10,13,16,19,23,26-octaoxo-9,22-dioxa-28-thia-2,5,12,15,18,25-hexaazabicyclo[12.12.3]nonacosane-7,20-diyl)bis(quinoxaline-2-carboxamide); 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-(81)-lactone-cyclic(37)-thioether; Antibiotic A 654I; NSC 13502; NSC 526417 |
| Storage | -20 °C |
| IUPAC Name | N-[(1R,4S,7R,11S,14R,17S,20R,24S)-2,4,12,15,17,25-hexamethyl-27-methylsulfanyl-3,6,10,13,16,19,23,26-octaoxo-11,24-di(propan-2-yl)-20-(quinoxaline-2-carbonylamino)-9,22-dioxa-28-thia-2,5,12,15,18,25-hexazabicyclo[12.12.3]nonacosan-7-yl]quinoxaline-2-carboxamide |
| Canonical SMILES | CC1C(=O)N(C2CSC(C(C(=O)N(C(C(=O)OCC(C(=O)N1)NC(=O)C3=NC4=CC=CC=C4N=C3)C(C)C)C)N(C(=O)C(NC(=O)C(COC(=O)C(N(C2=O)C)C(C)C)NC(=O)C5=NC6=CC=CC=C6N=C5)C)C)SC)C |
| InChI | 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 |
| InChI Key | AUJXLBOHYWTPFV-VITLIGDRSA-N |
| Source | Streptomyces sp. |
Properties
| Appearance | Colorless ribbed or micro Acicular Crystal |
| Antibiotic Activity Spectrum | Gram-positive bacteria; Neoplastics (Tumor); Parasites; Viruses |
| Boiling Point | 1427.2 °C at 760 mmHg |
| Melting Point | 127-128 °C |
| Density | 1.41 g/cm3 |
| Solubility | Soluble in Chloroform, DMSO, DMF; Insoluble in Methanol, Ethanol; Poorly soluble in Water |
Reference Reading
1. The HIF1α-PDGFD-PDGFRα axis controls glioblastoma growth at normoxia/mild-hypoxia and confers sensitivity to targeted therapy by echinomycin
Pengfei Ge, Yang Liu, Zhaoli Meng, Di Zhang, Yin Wang, Chong Qi, Peng Zhang, Junqi Niu, Yan Liu, Christopher Bailey, Qian Chen, Pan Zheng, Jingtao Chen, Gong Peng J Exp Clin Cancer Res . 2021 Sep 1;40(1):278. doi: 10.1186/s13046-021-02082-7.
Background:Glioblastoma multiforme (GBM), a lethal brain tumor, remains the most daunting challenge in cancer therapy. Overexpression and constitutive activation of PDGFs and PDGFRα are observed in most GBM; however, available inhibitors targeting isolated signaling pathways are minimally effective. Therefore, better understanding of crucial mechanisms underlying GBM is needed for developing more effective targeted therapies.Methods:Target genes controlled by HIF1α in GBM were identified by analysis of TCGA database and by RNA-sequencing of GBM cells with HIF1α knockout by sgRNA-Cas9 method. Functional roles of HIF1α, PDGFs and PDGFRs were elucidated by loss- or gain-of-function assays or chemical inhibitors, and compared in response to oxygen tension. Pharmacological efficacy and gene expression in mice with intracranial xenografts of primary GBM were analyzed by bioluminescence imaging and immunofluorescence.Results:HIF1α binds the PDGFD proximal promoter and PDGFRA intron enhancers in GBM cells under normoxia or mild-hypoxia to induce their expression and maintain constitutive activation of AKT signaling, which in turn increases HIF1α protein level and activity. Paradoxically, severe hypoxia abrogates PDGFRα expression despite enhancing HIF1α accumulation and corresponding PDGF-D expression. Knockout of HIF1A, PDGFD or PDGFRA in U251 cells inhibits cell growth and invasion in vitro and eradicates tumor growth in vivo. HIF1A knockdown in primary GBM extends survival of xenograft mice, whereas PDGFD overexpression in GL261 shortens survival. HIF1α inhibitor Echinomycin induces GBM cell apoptosis and effectively inhibits growth of GBM in vivo by simultaneously targeting HIF1α-PDGFD/PDGFRα-AKT feedforward pathway.Conclusions:HIF1α orchestrates expression of PDGF-D and PDGFRα for constitutive activation of AKT pathway and is crucial for GBM malignancy. Therefore, therapies targeting HIF1α should provide an effective treatment for GBM.
2. Echinomycin biosynthesis
Yuta Tsunematsu, Takehito Nakazawa, Kinya Hotta, Michio Sato, Kenji Watanabe Curr Opin Chem Biol . 2013 Aug;17(4):537-45. doi: 10.1016/j.cbpa.2013.06.022.
Echinomycin is an antitumor antibiotic secondary metabolite isolated from streptomycetes, whose core structure is biosynthesized by nonribosomal peptide synthetase (NRPS). The echinomycin biosynthetic pathway was successfully reconstituted in Escherichia coli. NRPS often contains a thioesterase domain at its C terminus for cyclorelease of the elongating peptide chain. Those thioesterase domains were shown to exhibit significant substrate tolerance. More recently, an oxidoreductase Ecm17, which forms the disulfide bridge in triostin A, was characterized. Surprisingly, an unrelated disulfide-forming enzyme GliT for gliotoxin biosynthesis was also able to catalyze the same reaction, providing another example of broad substrate specificity in secondary metabolite biosynthetic enzymes. Those promiscuous catalysts can be a valuable tool in generating diversity in natural products analogs we can produce heterologously.
3. Echinomycin
M J Waring Pathol Biol (Paris) . 1992 Dec;40(10):1022-34.
The story of echinomycin is of an antibiotic whose anti-cancer activity was rediscovered thanks to scientific investigation of its mode of action at the molecular level. It was the first DNA bis-intercalator identified (in 1974). Molecular models for echinomycin and its congeners are now well-founded on crystallographic data. These are beginning to throw light on significant variations in conformation which affect the ability of the antibiotics to recognise specific nucleotide sequences in DNA. Kinetic and other physical experiments have revealed much about the stability and selectivity of antibiotic-DNA complexes: stacking forces are important, as are hydrogen bonding interactions. Echinomycin preferentially recognises sites in DNA containing the CpG step, but other sites of lower occupancy exist and the antibiotic can migrate between them. Currently a good deal of attention is being paid to the suggestion that echinomycin might change Watson-Crick base pairs to a Hoogsteen form.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
