| Identification | Back Directory | [Name]
QUINOMYCIN A | [CAS]
512-64-1 | [Synonyms]
SK-302B
nsc526417
NSC 13502
ECHINOMYCIN
QUINOMYCIN A
echinomycina
Echinomycin >97%
Antibiotic A 654I
Echinomycin (NSC-13502)
EchinoMycin, Actinoleukin, 1491, 59266, X 948, X 53III
9,22-Dioxa-28-thia-2,5,12,15,18,25-hexaazabicyclo[12.12.3]nonacosane cyclic peptide deriv.
N-(2-Quinoxalinylcarbonyl)cyclo(D-Ser*-Ala-N-methyl-L-Cys(1)-N-methyl-L-Val-N-(quinoxaline-2-ylcarbonyl)-D-Ser*-Ala-N-methyl-3-methylthio-L-Ala(1)-N-methyl-L-Val-)
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)-thioester
N-[2,4,12,15,17,25-hexamethyl-29-methylsulfanyl-3,6,10,13,16,19,23,26-octaoxo-11,24-di(propan-2-yl)-7-(quinoxaline-2-carbonylamino)-9,22-dioxa-28-thia-2,5,12,15,18,25-hexazabicyclo[12.12.3]nonacosan-20-yl]quinoxaline-2-carboxamide
N-[(1R,4S,8R,11S,14R,17S,21R,24S)-3,11,13,16,24,26-hexamethyl-27-methylsulfanyl-2,5,9,12,15,18,22,25-octaoxo-4,17-di(propan-2-yl)-8-(quinoxaline-2-carbonylamino)-6,19-dioxa-28-thia-3,10,13,16,23,26-hexazabicyclo[12.12.3]nonacosan-21-yl]quinoxaline-2-carbo | [Molecular Formula]
C51H64N12O12S2 | [MDL Number]
MFCD00156105 | [MOL File]
512-64-1.mol | [Molecular Weight]
1101.26 |
| Chemical Properties | Back Directory | [Melting point ]
217-218℃ | [alpha ]
D20 -310° (c = 0.86 in chloroform) | [Boiling point ]
1427.2±65.0 °C(Predicted) | [density ]
1.0964 (rough estimate) | [refractive index ]
1.6700 (estimate) | [storage temp. ]
2-8°C
| [solubility ]
Soluble in DMSO (up to 5 mg/ml) | [form ]
White solid | [pka]
9.38±0.70(Predicted) | [color ]
white to beige | [Merck ]
13,3531 | [Stability:]
Stable for 1 year as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months | [InChIKey]
AUJXLBOHYWTPFV-UHFFFAOYSA-N | [SMILES]
S1C(C2N(C(=O)C(NC(=O)C(COC(=O)C(N(C(=O)C(N(C(=O)C(NC(=O)C(COC(=O)C(N(C2=O)C)C(C)C)NC(=O)c5nc6c(nc5)cccc6)C)C)C1)C)C(C)C)NC(=O)c3nc4c(nc3)cccc4)C)C)SC |
| Hazard Information | Back Directory | [Uses]
Quiniomycin A is a cyclic depsipeptide metabolite. Quinomycin A has broad activity against bacteria, fungi and viruses, and has found application as an antitumour agent. Quinomycin A acts by bifunctional intercalation of nucleic acids. Recent research has shown quinomycin A to be an extremely potent inhibitor of hypoxia-inducible factor-1 (HIF-1). This transcription factor plays an essential role in tumour progression and metastasis. | [Uses]
Quinomycin A is a cyclic depsipeptide metabolite. Quinomycin A has broad activity against bacteria, fungi and viruses, and has found application as an antitumor agent. Quinomycin A acts by bifunctional intercalation of nucleic acids. Recent research has shown quinomycin A to be an extremely potent inhibitor of hypoxia-inducible factor-1 (HIF-1). This transcription factor plays an essential role in tumor progression and metastasis. | [Description]
Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that controls genes involved in glycolysis, angiogenesis, migration, and invasion. Echinomycin is a cell-permeable inhibitor of HIF-1-mediated gene transcription. It acts by intercalating into DNA in a sequence-specific manner, blocking the binding of either HIF-1α or HIF-1β to the hypoxia-responsive element. Echinomycin reversibly inhibits hypoxia-induced HIF-1 transcription activity in U215 cells with an EC50 value of 1.2 nM. It inhibits hypoxia-induced expression of vascular endothelial growth factor, blocking angiogenesis and altering excitatory synaptic transmission in hippocampal neurons. Echinomycin also impairs expression of survivin, enhancing the sensitivity of multiple myeloma cells to melphalan. | [Biochem/physiol Actions]
Echinomycin is an antitumor antibiotic and potent hypoxia inducible factor 1α (HIF-1α) inhibitor. It binds to DNA via bifunctional intercalation, blocking the binding of HIF-1α, a transcription factor important in tumor growth. Echinomycin selectively eliminated cancer stem cells in a study with mouse lymphoma and human AML xenogeneic models, eradicating the lymphomas. Recently, echinomycin was also found to act as an antibiotic adjuvant having synergistic effects with novobiocin in gram negative bacteria. | [in vivo]
Echinomycin (10 μg/kg; intravenous injection; for 40 days; NOD-SCID mice) treatment efficiently eradicates mouse lymphoma and serially transplantable human acute myeloid leukemia (AML) in xenogeneic model by preferential elimination of cancer stem cells (CSCs). HIF1α maintains mouse lymphoma CSCs by repressing a negative feedback loop in the Notch pathway[2]. | Animal Model: | NOD-SCID mice received 1.8Gy of irradiation and i.v. injection with peripheral blood cells from patients AML-71 and AML-150[2] | | Dosage: | 10 μg/kg | | Administration: | Intravenous injection; for 40 days | | Result: | Efficiently eradicated mouse lymphoma and serially transplantable human AML in xenogeneic model by preferential elimination of CSCs.
|
| [storage]
Store at -20°C | [References]
1) Kong?et al.?(2005),?Echinomycin, a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity; Cancer Res.,?65?9047
2) Wang?et al. (2014),?Echinomycin protects mice against relapsed acute myeloid leukemia without adverse effect on hematopoietic stem cells; Blood,?124?1127
3) Wang?et al. (2011),?Targeting HIF1α eliminates cancer stem cells in hematological malignancies; Cell Stem Cell.,?8?399
4) Li?et al. (2015),?Hypoxia-inducible factor-1α regulates the expression of L-type voltage-dependent Ca(2+) channels in PC12 cells under hypoxia; Cell Stress Chaperones,?20?507 |
| Safety Data | Back Directory | [Hazard Codes ]
T | [Risk Statements ]
46-23/24/25 | [Safety Statements ]
53-36/37/39-45 | [RIDADR ]
UN 3462 6.1/PG 2
| [WGK Germany ]
3
| [RTECS ]
JW5250000
| [F ]
10 | [HazardClass ]
6.1(b) | [PackingGroup ]
III | [HS Code ]
2941900000 | [Storage Class]
6.1C - Combustible acute toxic Cat.3
toxic compounds or compounds which causing chronic effects | [Hazard Classifications]
Acute Tox. 3 Dermal
Acute Tox. 3 Inhalation
Acute Tox. 3 Oral
Repr. 2 |
|
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T&W GROUP
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Sigma-Aldrich
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Lynnchem
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Nextpeptide Inc
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http://www.nextpeptide.com/ |
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Shaanxi Dideu Medichem Co. Ltd
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+86-29-87569266 +86-17392581500 |
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https://www.chemicalbook.com/manufacturer/shaanxi-dideu-medichem-220/ |
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Energy Chemical
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021-58432009 400-005-6266 |
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http://www.energy-chemical.com |
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