Chetomin (Synonyms: NSC 289491) |
Catalog No.GC17405 |
An inhibitor of HIF signaling
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1403-36-7
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >95.00%
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- SDS (Safety Data Sheet)
- Datasheet
Chetomin, an antibiotic metabolite of chaetomium cochliodes, is an inhibitor of HIF-1 by weaken transcription of HIF-1 and recently is raised interests as a cancer chemotherapeutic agent.[1]
HIF-1 (hypoxia-inducible factors 1) is transcription factor which respond to changes of cellular environment oxygen. [2] HIF-1 complex belongs to the PAS subfamily of the basic helix-loop-helix family of transcription factors and is composed of an alpha subunit and a beta subunit which formed a heterodimer. [3] HIF-1 can upregulate several genes such as glycolysis enzymes, vascular endothelial growth factor to promote survival rate of cells in hopoxia conditions through binding to HIF-responsive elements in the promoters. NF- Kappa B was shown a direct modulator of HIF-1alpha in normal condition but in low-oxygen conditions HIF-1alpha still stable with an unknown mechanism. [4]
Chetomin selectively inhibited HIF-1 activities through disruption of the interaction of HIF-1with its transcriptional coactivator p300. Early-passage human fibrosarcoma HT1080 cells stably transfected EGFP plasmid with a hypoxia-responsive 5HRE-hCMVmp promoter were pretreated with chetomin showed dose and incubation-time dependent EGFP fluorescence signal suppression. And pretreatment of 150nM chetomin for 4h showed maximum suppressive effects, indicated the inhibition of HIF-dependent transcription. Also, 150nM chetomin decreased expression of VEGF and CA9 under hapoxic conditions in HT1010 cells. Chetomin increased cell survival rate under hypoxia compared mormoxia conditions, indicated that chetomin can enhanced radiation treatment efficacy under severely hypoxic conditions.[5]
References:
[1] Timothy R. Welch and Robert M. Williams. Studies on the Biosynthesis of Chetomin: Enantiospecific Synthesis of a Putative, Late-Stage Biosynthetic Intermediate. Tetrahedron (2013) 69(2): 770–773
[2] Smith TG, Robbins PA, Ratcliffe PJ. The human side of hypoxia-inducible factor. Br. J. Haematol. (2008)141(3): 325–34
[3] Jiang BH, Rue E, Wang GL, Roe R, Semenza GL. Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1. J. Biol. Chem. (1996) 271(30):17771-17778
[4] Van Uden P, Kenneth NS, Rocha S. Regulation of hypoxia-inducible factor-1 alpha by NF-kappa B. Biochem. J. (2008) 412(3): 477-484
[5] Adrian Staab, Jürgen Loeffler, Harun M Said, Désirée Diehlmann, Astrid Katzer, Melanie Beyer, Markus Fleischer, Franz Schwab, Kurt Baier, Hermann Einsele, Michael Flentje and Dirk Vordermark. Effects of HIF-1 inhibition by chetomin on hypoxia-related transcription and radiosensitivity in HT 1080 human fibrosarcoma Cells. BMC Cancer (2007) 7 :213
Cas No. | 1403-36-7 | SDF | |
Synonyms | NSC 289491 | ||
Chemical Name | (3S,5aR,10bS,11aS)-2,3,5a,6,10b,11-hexahydro-3-(hydroxymethyl)-10b-(3-[(1S,4S)-3-[[4-(hydroxymethyl)-5,7-dimethyl-6,8-dioxo-2,3-dithia-5,7-diazabicyclo[2.2.2]oct-1-yl)methyl]-1H-indol-1-yl]-2-methyl-3,11a-epidithio-11aH-pyrazino[1,2:1,5]pyrrolo[2,3-b]indo | ||
Canonical SMILES | O=C([C@@](N1C)(SS2)CC3=CN([C@@]([C@]4([H])N5)(C[C@@]6(SS7)N4C([C@@]7(CO)N(C)C6=O)=O)C8=C5C=CC=C8)C9=C3C=CC=C9)N(C)[C@]2(CO)C1=O | ||
Formula | C31H30N6O6S4 | M.Wt | 710.87 |
Solubility | 5mg/mL in DMSO | Storage | Store at -20°C |
General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. |
Prepare stock solution | |||
1 mg | 5 mg | 10 mg | |
1 mM | 1.4067 mL | 7.0336 mL | 14.0673 mL |
5 mM | 0.2813 mL | 1.4067 mL | 2.8135 mL |
10 mM | 0.1407 mL | 0.7034 mL | 1.4067 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
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