Echinomycin

Names

[ CAS No. ]:
512-64-1

[ Name ]:
Echinomycin

[Synonym ]:
echinomycin
quinomycin-A

Biological Activity

[Description]:

Echinomycin (Quinomycin A) is potent small-molecule and cell-permeable inhibitor of hypoxia-inducible factor-1 (HIF-1) DNA-binding activity. Echinomycin selectively inhibits the cancer stem cells (CSCs) with an IC50 of 29.4 pM[1][2].

[Related Catalog]:

Research Areas >> Cancer

[In Vitro]

Echinomycin (0-10 nM; 16 hours; U251 cells) treatment significantly inhibits hypoxia-induced VEGF mRNA expression in a dose-dependent fashion. Echinomycin very potently inhibits hypoxic induction of luciferase expression in U251-HRE in a dose-dependent fashion with an EC50 of 1.2 nM[1]. RT-PCR[1] Cell Line: U251 cells Concentration: 0 nM, 0.625 nM, 1.25 nM, 5 nM, 10 nM Incubation Time: 16 hours Result: Significantly inhibited VEGF mRNA expression induced by hypoxia in a dose-dependent fashion.

[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.

[References]

[1]. Kong D, et al. Echinomycin, a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity. Cancer Res. 2005 Oct 1;65(19):9047-55.

[2]. Wang Y, et al. Targeting HIF1α eliminates cancer stem cells in hematological malignancies. Cell Stem Cell. 2011 Apr 8;8(4):399-411.

Chemical & Physical Properties

[ Density]:
1.41 g/cm3

[ Boiling Point ]:
1427.2ºC at 760 mmHg

[ Molecular Formula ]:
C₅₁H₆₄N₁₂O₁₂S₂

[ Molecular Weight ]:
1101.26000

[ Flash Point ]:
817ºC

[ Exact Mass ]:
1100.42000

[ PSA ]:
352.40000

[ LogP ]:
1.82630

[ Index of Refraction ]:
1.536

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: JW5250000

CHEMICAL NAME :: Echinomycin

CAS REGISTRY NUMBER :: 512-64-1

BEILSTEIN REFERENCE NO. :: 0078671

LAST UPDATED :: 199712

DATA ITEMS CITED :: 7

MOLECULAR FORMULA :: C51-H64-N12-O12-S2

MOLECULAR WEIGHT :: 1101.39

WISWESSER LINE NOTATION :: T C-16-6-16-/CE& A B C- C-- 2CP E& AS CX C-S DNV GMV KOV NNV PXNV TMV A&OV D&NVTJ D1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 280 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 3800 ug/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 629 ug/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - ataxia Skin and Appendages - hair

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 89 ug/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - ataxia Gastrointestinal - nausea or vomiting

MUTATION DATA

TYPE OF TEST :: DNA inhibition

TEST SYSTEM :: Mammal - species unspecified Lymphocyte

DOSE/DURATION :: 27 umol/L

REFERENCE :: HXPHAU Handbuch der Experimentellen Pharmakologie. (Berlin, Ger.) New series: V.1-49, 1935-78. For publisher information, see HEPHD2. Volume(issue)/page/year: 38(Pt 2),623,1975

Safety Information

[ Symbol ]:

GHS06, GHS08

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301 + H311 + H331-H361

[ Precautionary Statements ]:
P261-P280-P301 + P310-P311

[ Hazard Codes ]:
T: Toxic;

[ Risk Phrases ]:
R46

[ Safety Phrases ]:
53-36/37/39-45

[ RIDADR ]:
UN 3462 6.1/PG 2

[ WGK Germany ]:
3

[ RTECS ]:
JW5250000

[ Packaging Group ]:
III

[ Hazard Class ]:
6.1(b)

Articles

Regulatory effect of hypoxia-inducible factor-1α on hCG-stimulated endothelin-2 expression in granulosa cells from the PMSG-treated rat ovary.

J. Reprod. Dev. 58(6) , 678-84, (2012)

Endothelin (ET)-2 plays a crucial role in ovarian ovulation in mammals. The present study was designed to test the hypothesis that hypoxia-inducible factor (HIF)-1α-mediated transcriptional activation...

Interaction of an echinomycin-DNA complex with manganese ions.

Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 65(Pt 7) , 660-4, (2009)

The crystal structure of an echinomycin-d(ACGTACGT) duplex interacting with manganese(II) was solved by Mn-SAD using in-house data and refined to 1.1 A resolution against synchrotron data. This comple...

Effects of echinomycin on endothelin-2 expression and ovulation in immature rats primed with gonadotropins.

Exp. Mol. Med. 44(10) , 615-21, (2012)

Echinomycin is a small-molecule inhibitor of hypoxia- inducible factor-1 DNA-binding activity, which plays a crucial role in ovarian ovulation in mammalians. The present study was designed to test the...

Related Compounds

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