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Siomycin A

Names

[ CAS No. ]:
12656-09-6

[ Name ]:
Siomycin A

[Synonym ]:
siomycin A
Antibiotic 6741-21,Mutabillicin,Mutabilycin
(1-L-valine)-[2-(2,3-didehydro-alanine)]-thiostrepton
N-{3-[(3-Amino-3-oxo-1-propen-2-yl)amino]-3-oxo-1-propen-2-yl}-2-[(11Z)-18-(2,3-dihydroxy-2-butanyl)-11-ethylidene-59-hydroxy-8,31-bis(1-hydroxyethyl)-37-isopropyl-26,46-dimethyl-40,43-bis(methylene)- ;6,9,16,23,28,38,41,44,47-nonaoxo-27-oxa-3,13,20,56-tetrathia-7,10,17,24,36,39,42,45,48,52,58,61,62,63,64-pentadecaazanonacyclo[23.23.9.3.1.1.1.1.0.0]tetra hexaconta-2(64),4,12(63),19(62),21,29,31,33,

Biological Activity

[Description]:

Siomycin A is a thiopeptide antibiotic and is a Forkhead box M1(FOXM1) selective inhibitor without affecting other members of the Forkhead box family. Siomycin A has anti-tumor and promotes apoptosis[1][2].

[Related Catalog]:

Signaling Pathways >> Apoptosis >> Apoptosis
Research Areas >> Cancer
Signaling Pathways >> Anti-infection >> Bacterial

[Target]

Forkhead box M1(FOXM1)[1]


[In Vitro]

Siomycin A (0-10 µM; 24-72 hours; K562, MCF7 and MiaPaCa-2 cells) treatment markedly reduces cell viability in a dose-dependent and a time-dependent association in K562, MCF7 and MiaPaCa-2 cells. Among the three cell lines, the IC50 of the human leukemia K562 cells is the lowest at 6.25 µM at 24 h, while that for the human pancreatic cancer MiaPaCa-2 cells is 6.38 µM. However, the IC50 of the human pancreatic cancer MiaPaCa-2 cells at 48 and 72 h are the lowest of the three cell lines, which are 0.76 and 0.54 µM, respectively[1]. Siomycin A (0-10 µM; MiaPaCa-2 cells) treatment has potent proapoptotic effect in MiaPaCa-2 cells[1]. Siomycin A (0-10 µM; 24 hours; MiaPaCa-2 cells) treatment significantly reduces the expression levels of MMP-2, MMP-9 and α-tubulin protein in the MiaPaCa-2 cells[1]. Cell Viability Assay[1] Cell Line: K562, MCF7 and MiaPaCa-2 cells Concentration: 0 µM, 0.625 µM, 1.25 µM, 2.5 µM, 5 µM or 10 µM Incubation Time: 24, 48 and 72 hours Result: Cell viability was markedly reduced in a dose-dependent and a time-dependent association. Apoptosis Analysis[1] Cell Line: MiaPaCa-2 cells Concentration: 0 µM, 0.625 µM, 1.25 µM, 2.5 µM, 5 µM or 10 µM Incubation Time: Result: Promoted apoptosis of MiaPaCa-2 cells. Western Blot Analysis[1] Cell Line: MiaPaCa-2 cells Concentration: 0 µM, 0.625 µM, 1.25 µM, 2.5 µM, 5 µM or 10 µM Incubation Time: 24 hours Result: The expression levels of MMP-2 and MMP-9 protein in the MiaPaCa-2 cells were significantly reduced in the 2.5, 5 and 10 µM groups.

[In Vivo]

Siomycin A (1 µM; subcutaneous injection; for 4 weeks; male Balb/c nude mice) pretreatment decreases tumour growth in an in vivo mouse model[2]. Animal Model: Four- to five-week old male Balb/c nude mice with IOMM-LEE cells[2] Dosage: 1 µM-pretreated IOMM-Lee cells Administration: Subcutaneous injection; for 4 weeks Result: Decreased tumour growth in an in vivo mouse model.

[References]

[1]. Wang B, et al. Effects and mechanism of siomycin A on the growth and apoptosis of MiaPaCa-2 cancer cells. Oncol Lett. 2019 Sep;18(3):2869-2876.

[2]. Kim H, et al. Forkhead box M1 (FOXM1) transcription factor is a key oncogenic driver of aggressive human meningioma progression. Neuropathol Appl Neurobiol. 2019 Jun 9.

Chemical & Physical Properties

[ Density]:
1.7±0.1 g/cm3

[ Molecular Formula ]:
C71H81N19O18S5

[ Molecular Weight ]:
1648.844

[ Exact Mass ]:
1647.461060

[ PSA ]:
701.00000

[ LogP ]:
-8.95

[ Index of Refraction ]:
1.773

MSDS

Safety Information

[ RIDADR ]:
NONH for all modes of transport

Articles

A novel mode of FoxM1 regulation: positive auto-regulatory loop.

Cell Cycle 8(12) , 1966-7, (2009)

Oncogenic transcription factor FoxM1 represents an attractive therapeutic target in the fight against cancer, because it is overexpressed in a majority of human tumors. Previously, we identified the t...

Thiazole antibiotics target FoxM1 and induce apoptosis in human cancer cells.

PLoS ONE 4(5) , e5592, (2009)

Forkhead box M1 (FoxM1) oncogenic transcription factor represents an attractive therapeutic target in the fight against cancer, because it is overexpressed in a majority of human tumors. Recently, usi...

The maternal embryonic leucine zipper kinase (MELK) is upregulated in high-grade prostate cancer.

J. Mol. Med. 91(2) , 237-48, (2013)

Loss of cell cycle control is a prerequisite for cancer onset and progression. In prostate cancer, increased activity of cell cycle genes has been associated with prognostic parameters such as biochem...


More Articles


Related Compounds

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