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echinomycin

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Description

Echinomycin: A cytotoxic polypeptide quinoxaline antibiotic isolated from Streptomyces echinatus that binds to DNA and inhibits RNA synthesis. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID23724556
CHEBI ID80052
MeSH IDM0006965

Synonyms (7)

Synonym
quinomycin a
512-64-1
echinomycin
CHEBI:80052
Q27149203
n-[(7r,20r)-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
PD118071

Research Excerpts

Overview

Echinomycin is an antitumor antibiotic secondary metabolite isolated from streptomycetes, whose core structure is biosynthesized by nonribosomal peptide synthetase (NRPS) It is a natural depsipeptide, which is a bisintercalator, inserting quinoxaline units preferentially adjacent to CG base pairs of DNA. Echinomytin is a known inhibitor of HIF-1-alpha and was used in our study with the aim to prevent HO from forming.

ExcerptReferenceRelevance
"Echinomycin is a natural product DNA bisintercalator antibiotic. "( Structural and functional analyses of the echinomycin resistance conferring protein Ecm16 from Streptomyces lasalocidi.
Chen, X; Erlandson, A; Gade, P; Kim, CY; Mathews, II; Mera, PE; Ullah, A, 2023
)
2.62
"Echinomycin is an antitumor antibiotic secondary metabolite isolated from streptomycetes, whose core structure is biosynthesized by nonribosomal peptide synthetase (NRPS). "( Echinomycin biosynthesis.
Hotta, K; Nakazawa, T; Sato, M; Tsunematsu, Y; Watanabe, K, 2013
)
3.28
"Echinomycin is a nonribosomal depsipeptide natural product with a range of interesting bioactivities that make it an important target for drug discovery and development. "( Conversion of a disulfide bond into a thioacetal group during echinomycin biosynthesis.
Bibby, J; Fang, M; Hotta, K; Keegan, RM; Kim, CY; Lian, M; Ranganathan, S; Rigden, DJ; Sato, M; Watanabe, K; Winn, MD, 2014
)
2.09
"Echinomycin is a natural depsipeptide, which is a bisintercalator, inserting quinoxaline units preferentially adjacent to CG base pairs of DNA. "( Towards echinomycin mimetics by grafting quinoxaline residues on glycophane scaffolds.
Eriksson, LA; Jarikote, DV; Jiang, T; Li, W; Murphy, PV, 2011
)
2.25
"Echinomycin is a small-molecule inhibitor of hypoxia- inducible factor-1 DNA-binding activity, which plays a crucial role in ovarian ovulation in mammalians. "( Effects of echinomycin on endothelin-2 expression and ovulation in immature rats primed with gonadotropins.
Chen, J; Chen, L; Cheng, Y; Huang, X; Luo, Q; Luo, Z; Wang, Z; Wu, Y; Zhang, J; Zhang, Z, 2012
)
2.21
"Echinomycin is a known inhibitor of HIF-1-alpha and was used in our study with the aim to prevent HO from forming."( Echinomycin in the prevention of heterotopic ossification - an experimental antibiotic agent shows promising results in a murine model.
Simmen, HP; Wanner, GA; Werner, CM; Würgler-Hauri, CC; Zimmermann, SM, 2013
)
2.55
"Echinomycin is a bifunctional DNA intercalating agent with broad preclinical antitumor activity."( Phase II study of echinomycin in the treatment of renal cell carcinoma ECOG study E2885.
Bryan, GT; Chang, AY; Kirkwood, JM; Oken, MM; Trump, DL; Tu, ZN, 1994
)
1.34
"Echinomycin is a novel bifunctional intercalating agent derived from Streptomyces echinatus. "( Phase II trial of echinomycin in patients with advanced or recurrent colorectal cancer.
Cazenave, L; Greenwald, ES; Kaleya, R; Rozenblit, A; Sparano, JA; Tenteromano, L; Wadler, S; Wiernik, PH, 1994
)
2.07
"Echinomycin is a potent bifunctional intercalator of double-strand DNA; trimetrexate is a new derivative of methotrexate and is active against methotrexate-resistant tumor cells in vitro."( A randomized phase II trial of echinomycin, trimetrexate, and cisplatin plus etoposide in patients with metastatic nonsmall cell lung carcinoma: an Eastern Cooperative Oncology Group Study (E1587).
Blum, RH; Bonomi, P; Boucher, H; Chang, AY; Karp, DD; Kim, K; Stewart, JA, 1998
)
1.31
"Echinomycin is a peptide antibiotic which binds strongly to double-helical DNA up to a limit of approximately one molecule per five base-pairs. "( The binding of echinomycin to deoxyribonucleic acid.
Wakelin, SP; Waring, MJ, 1976
)
2.05
"Echinomycin is a quinoxaline antibiotic that was originally isolated from Streptomyces echinatus. "( Echinomycin: the first bifunctional intercalating agent in clinical trials.
Clagett-Carr, K; Foster, BJ; Grieshaber, CK; Leyland-Jones, B; Plowman, J; Shoemaker, DD; Suffness, M; Trissel, LA, 1985
)
3.15

Actions

Echinomycin was used to inhibit hypoxia-inducible factor-1 (HIF-1) alpha activity.

ExcerptReferenceRelevance
"Echinomycin was used to inhibit hypoxia-inducible factor-1 (HIF-1) alpha activity."( L-mimosine increases the production of vascular endothelial growth factor in human tooth slice organ culture model.
Agis, H; Cvikl, B; Gruber, R; Moritz, A; Müller, HD; Nürnberger, S; Trimmel, K, 2015
)
1.14
"Echinomycin displays minimal activity as salvage therapy in women with advanced ovarian cancer at this dose and schedule."( Echinomycin (NSC 526417) in advanced ovarian cancer. A phase II trial of the Gynecologic Oncology Group.
Adelson, MD; Baker, VV; Barnhill, DR; Blessing, JA; Muss, HB, 1990
)
2.44

Treatment

Echinomycin treatment reduces aGVHD and preserves GVL effect via increasing donor Treg development. Treatment also induces viral lytic gene expression whereas not increasing infectious virions production from KSHV + tumor cells.

ExcerptReferenceRelevance
"Echinomycin treatment also induces viral lytic gene expression whereas not increasing infectious virions production from KSHV + tumor cells."( Echinomycin as a promising therapeutic agent against KSHV-related malignancies.
Chen, J; Dai, L; James, J; Lin, Z; Mu, S; Plaisance-Bonstaff, K; Post, SR; Qin, Z; Song, J, 2023
)
3.07
"Echinomycin treatment reduces aGVHD and preserves GVL effect via increasing donor Treg development and diminishing alloantigen-specific Th17 and Th1 responses following allo-HSCT, presumably via direct inhibition of HIF-1α that results in preferential Treg differentiation during alloantigen-specific CD4 T cell responses. "( HIF-1α inhibitor echinomycin reduces acute graft-versus-host disease and preserves graft-versus-leukemia effect.
Wang, L; Yao, Y; Zhang, X; Zhou, J, 2017
)
2.24
"Echinomycin treatment failed to produce type II products, probably because of a DNA-binding affinity weaker than that of luzopeptin A."( Intermolecular cross-linking of DNA through bifunctional intercalation of an antitumor antibiotic, luzopeptin A (BBM-928A).
Crooke, ST; Huang, CH; Mirabelli, CK; Mong, S, 1983
)
0.99
"Treatment with echinomycin suppressed cell growth and induced apoptosis in association with decreased mRNA expression of HIF1 targets, glucose transporter-1 (GLUT1) and B-cell CLL/lymphoma-2 (BCL2)."( Effects of the HIF1 inhibitor, echinomycin, on growth and NOTCH signalling in leukaemia cells.
Itoh, M; Nara, N; Okuhashi, Y; Ono, A; Takahashi, Y; Tohda, S; Yonekura, S, 2013
)
1.02

Toxicity

ExcerptReferenceRelevance
" However, due to overlap in their self-renewal program with normal hematopoietic stem cells (HSCs), therapeutic targeting of the LIC may have an adverse effect on long-term hematopoietic recovery."( Echinomycin protects mice against relapsed acute myeloid leukemia without adverse effect on hematopoietic stem cells.
Bernot, KM; Caligiuri, MA; Liu, Y; Marcucci, G; Schore, R; Tang, F; Wang, Y; Zheng, P, 2014
)
1.85

Dosage Studied

Twenty-two patients with recurrent carcinoma of the ovary progressive after initial chemotherapy (21 with cisplatin-based treatment) were entered on a phase II trial utilizing Echinomycin at a dosage of 1,500 micrograms/m2 every 4 weeks.

ExcerptRelevanceReference
"Twenty-two patients with recurrent carcinoma of the ovary progressive after initial chemotherapy (21 with cisplatin-based treatment) were entered on a phase II trial utilizing Echinomycin at a dosage of 1,500 micrograms/m2 every 4 weeks."( Echinomycin (NSC 526417) in advanced ovarian cancer. A phase II trial of the Gynecologic Oncology Group.
Adelson, MD; Baker, VV; Barnhill, DR; Blessing, JA; Muss, HB, 1990
)
1.91
" Thrombocytopenia was noted in 15% of patients receiving greater than or equal to 700 micrograms/m2 and was severe in 11% without an evident dose-response relationship."( Phase I study of echinomycin.
Baker, LH; Decker, D; Haas, CD; Leichman, CG; Pazdur, R, 1987
)
0.61
" Pharmacokinetic analysis showed that thiocoraline has distinct pharmacokinetic profiling when dosed in different formulation solutions."( Validation of a sensitive assay for thiocoraline in mouse plasma using liquid chromatography-tandem mass spectrometry.
Aviles, P; Calvo, P; Faircloth, G; Guillen, MJ; Lee, W; Ly, C; Manzanares, I; Yin, J, 2003
)
0.32
" Further studies have yet to be conducted to optimise the results by altering the dosage and duration of administration as well as investigate the mechanism by which Echinomycin led to the reduction of HO formation."( Echinomycin in the prevention of heterotopic ossification - an experimental antibiotic agent shows promising results in a murine model.
Simmen, HP; Wanner, GA; Werner, CM; Würgler-Hauri, CC; Zimmermann, SM, 2013
)
2.03
" In this study, echinomycin exhibited strong anti-Mycobacterium tuberculosis H37Rv activity and synergistic antifungal effect with a greatly reduced dosage of posaconazole on Candida albicans SC5314."( Characterization of Streptomyces sp. LS462 with high productivity of echinomycin, a potent antituberculosis and synergistic antifungal antibiotic.
Abdel-Mageed, WM; Chen, C; Chen, X; Guo, H; Liu, X; Ren, B; Song, F; Zhang, L, 2021
)
1.2
"Combination cancer chemotherapy is one of the most useful treatment methods to achieve a synergistic effect and reduce the toxicity of dosing with a single drug."( Synergistic binding of actinomycin D and echinomycin to DNA mismatch sites and their combined anti-tumour effects.
Chang, CC; Hou, MH; Li, LY; Lin, SH; Neidle, S; Satange, R, 2023
)
1.18
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
cyclodepsipeptideA depsipeptide in which the amino and hydroxy carboxylic acid residues are connected in a ring.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Research

Studies (274)

TimeframeStudies, This Drug (%)All Drugs %
pre-199076 (27.74)18.7374
1990's68 (24.82)18.2507
2000's50 (18.25)29.6817
2010's50 (18.25)24.3611
2020's30 (10.95)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 29.95

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index29.95 (24.57)
Research Supply Index5.70 (2.92)
Research Growth Index4.62 (4.65)
Search Engine Demand Index42.09 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (29.95)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials16 (5.65%)5.53%
Reviews15 (5.30%)6.00%
Case Studies1 (0.35%)4.05%
Observational0 (0.00%)0.25%
Other251 (88.69%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]