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Nanaomycin ADNMT3B inhibitor

Nanaomycin A

Catalog No. BCC3611
Size Price Stock
5mg $350.00 In stock
25mg $1,000.00 In stock
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Quality Control of Nanaomycin A

Chemical structure

Nanaomycin A

Biological Activity of Nanaomycin A

Description Nanaomycin A is a selective inhibitor of DNMT3B.
Targets DNMT3B          
IC50 500 nM          

Protocol

Cell experiment[1]:

Cell lines

A549, HL60, HeLa and HCT116 cells 

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reacting condition

Ranging from 10 nM to 10 μM for 72 h

Applications

Nanaomycin A, initially identified by a virtual screening for inhibitors against DNMT1, as a compound inducing antiproliferative effects in three different tumor cell lines originating from different tissues. Nanaomycin A treatment reduced the global methylation levels in all three cell lines and reactivated transcription of the RASSF1A tumor suppressor gene. In biochemical assays, nanaomycin A revealed selectivity toward DNMT3B.

Animal experiment [2]:

Animal models

Guinea pigs

Application

The therapeutic effect of nanaomycin A and siccanin against experimental cutaneous Trichophyton mentagrophytes infection in guinea pigs was investigated. Topically applied formulation of nanaomycin A was very effective in improving the condition of lesions and in preventing fungal growth in the infected tissues. Nanaomycin A and siccanin were comparable in activity in experiments.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

1. Kuck D1, Caulfield T, Lyko F et al. Nanaomycin A selectively inhibits DNMT3B and reactivates silenced tumor suppressor genes in human cancer cells. Mol Cancer Ther. 2010 Nov;9(11):3015-23.

2. Kitaura K, Araki Y, Marumo H. The therapeutic effect of nanaomycin A against experimental Trichophyton mentagrophytes infection in guinea pigs. Kitaura K, Araki Y, Marumo H.

Nanaomycin A Dilution Calculator

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Chemical Properties of Nanaomycin A

Cas No. 52934-83-5 SDF Download SDF
Chemical Name 2-[(1S,3R)-9-hydroxy-1-methyl-5,10-dioxo-3,4-dihydro-1H-benzo[g]isochromen-3-yl]acetic acid
SMILES C[C@@H]1O[C@@H](CC(O)=O)CC2=C1C(=O)c3c(O)cccc3C2=O
Standard InChIKey ZCJHPTKRISJQTN-JGVFFNPUSA-N
Standard InChI InChI=1S/C16H14O6/c1-7-13-10(5-8(22-7)6-12(18)19)15(20)9-3-2-4-11(17)14(9)16(13)21/h2-4,7-8,17H,5-6H2,1H3,(H,18,19)/t7-,8+/m0/s1
Formula C16H14O6 M.Wt 302.28
Solubility Soluble in Methanol
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other courier with RT , or blue ice upon request.

Preparing Stock Solutions of Nanaomycin A

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 3.3082 mL 16.541 mL 33.0819 mL 66.1638 mL 82.7048 mL
5 mM 0.6616 mL 3.3082 mL 6.6164 mL 13.2328 mL 16.541 mL
10 mM 0.3308 mL 1.6541 mL 3.3082 mL 6.6164 mL 8.2705 mL
50 mM 0.0662 mL 0.3308 mL 0.6616 mL 1.3233 mL 1.6541 mL
100 mM 0.0331 mL 0.1654 mL 0.3308 mL 0.6616 mL 0.827 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

Background on Nanaomycin A

Nanaomycin A is a selective inhibitor of DNA methyltransferase 3B (DNMT3B) with IC50 value of 500 nM [1].

In the biochemical in vitro methylation assay, Nanaomycin A showed selective inhibition of DNMT3B but not DNMT1 although it was docked to the catalytic domain of human DNMT1 in a multi-step docking approach. Nanaomycin A showed cell viability inhibition in HCT116, A549 and HL60 cells with IC50 values of 400 nM, 4100 nM and 800 nM, respectively. It decreased the genomic methylation level of these cells significantly. Besides that, Nanaomycin A treatment resulted in demethylation of the RASSF1A promoter in A549 cells. The demethylation caused by Nanaomycin A reactivated the transcription and expression of a silenced tumor suppressor gene [1].

References:
[1] Kuck D, Caulfield T, Lyko F, et al. Nanaomycin A selectively inhibits DNMT3B and reactivates silenced tumor suppressor genes in human cancer cells. Molecular cancer therapeutics, 2010, 9(11): 3015-3023.

References on Nanaomycin A

Nanaomycin H: A new nanaomycin analog.[Pubmed: 28202308]


Physicochemical screening identified a new nanaomycin analog, nanaomycin H, which was isolated from a culture broth of Streptomyces rosa subsp. notoensis OS-3966. This microorganism is already known to produce seven nanaomycin compounds, (nanaomycin A to G). Structural elucidation of nanaomycin H showed it to be a pyranonaphthoquinone with a mycothiol moiety. A N-acetylcysteine S-conjugate of nanaomycin H, without α-glucosamine linked to myo-inositol moiety, mercapturic acid derivative, was also detected in the same culture broth. Mercapturic acid derivatives of secondary metabolites are known to be produced for xenobiotic metabolism outside microbial cells. Mycothiol acts as a detoxifier to help prevent cell damage from factors such as oxidative stress. The production of O2- generated by reduction of nanaomycin A is correlated with antibacterial activity. Mycothiol-containing nanaomycin H proved to be markedly decreased in O2- and did not express any notable antimicrobial activity. It is suggested that nanaomycin H is produced in the detoxification process.

New compounds, nanaomycin F and G, discovered by physicochemical screening from a culture broth of Streptomyces rosa subsp. notoensis OS-3966.[Pubmed: 26100318]


Two new compounds, nanaomycin F and G, were isolated by physicochemical screening method from cultured broth of Streptomyces rosa subsp. notoensis OS-3966, which is known to produce nanaomycin A, B, C, D, and E. Nanaomycin F is a new nanaomycin analog, a 4a-hydroxyl analog of nanaomycin B. Nanaomycin G has a unique skeleton with 1-indanone infused with a tetrahydropyran ring. Nanaomycin A possesses broad antimicrobial activity but nanaomycin F and G demonstrated no bioactivity against all bacteria and fungi tested in this study. In addition, in both nanaomycin F and G, the production of superoxide radicals was majorly decreased in comparison to nanaomycin A. It was considered that the antimicrobial properties were lost as a result of the decrease in production of the superoxide radicals.

Molecular dynamics simulations of human DNA methyltransferase 3B with selective inhibitor nanaomycin A.[Pubmed: 21839172]


DNA methyltransferases (DNMTs) are involved in epigenetic regulation of the genome and are promising targets for therapeutic intervention in cancer and other diseases. Until now, very limited information is available concerning the molecular dynamics of DNMTs. The natural product nanaomycin A is the first selective inhibitor of DNMT3B that induce genomic demethylation. Herein we report long (>100ns) molecular dynamics simulations for human DNMT3B bound to nanaomycin A with and without the presence of the cofactor S-adenosyl-L-methionine (SAM). We concluded that SAM favors the binding of nanaomycin A to DNMT3B. Key interactions of nanaomycin A with DNMT3B involve long lasting interactions with Arg731, Arg733, Arg832, and the catalytic Cys651. Results further support the previous hypothesis that nanaomycin A has key interactions with amino acid residues involved in the mechanism of methylation. This work represents one of the first molecular dynamics studies of DNMT3B. Results of this work shed light on the structure and binding recognition process of a key epigenetic enzyme with a small molecule inhibitor.

Nanaomycin A selectively inhibits DNMT3B and reactivates silenced tumor suppressor genes in human cancer cells.[Pubmed: 20833755]


Enzymes involved in the epigenetic regulation of the genome represent promising starting points for therapeutic intervention by small molecules, and DNA methyltransferases (DNMT) are emerging targets for the development of a new class of cancer therapeutics. In this work, we present nanaomycin A, initially identified by a virtual screening for inhibitors against DNMT1, as a compound inducing antiproliferative effects in three different tumor cell lines originating from different tissues. Nanaomycin A treatment reduced the global methylation levels in all three cell lines and reactivated transcription of the RASSF1A tumor suppressor gene. In biochemical assays, nanaomycin A revealed selectivity toward DNMT3B. To the best of our knowledge, this is the first DNMT3B-selective inhibitor identified to induce genomic demethylation. Our study thus establishes the possibility of selectively inhibiting individual DNMT enzymes.

Kewords:

Nanaomycin A,52934-83-5,Chromatin/Epigenetics,DNA Methyltransferase, supplier, inhibitor,Antagonist,Blocker,Modulator,Agonist, activators, activates, potent, BioCrick

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