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| Targets |
Nanafrocin selectively inhibits DNA methyltransferase 3B (DNMT3B) with an IC50 of 500 nM. It does not inhibit DNMT1 enzymatic activity. By inhibiting DNMT3B, Nanafrocin reduces DNA methylation levels and reactivates silenced tumor suppressor genes such as RASSF1A. The compound also has antibacterial activity against Gram-negative anaerobes and inhibits malaria and trypanosomes. Within organisms, Nanafrocin is first reduced by flavin or NADH dehydrogenase, then rapidly autooxidized, producing singlet molecular oxygen (O2-).
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| ln Vitro |
All three cell lines are significantly cytotoxically affected by nanoomycin A (10–10,000 nM; 72 hours) [1]. In A549 cells, nanoomycin A (0.5, 5 μM; 72 hours) induces the production of the RASSF1A protein [1]. The relative induction of nanoomycin A (5 μM; 72 hours) is 18-fold [1]. No effect of nanoomycin A has been seen on DNMT1's enzymatic activity [1].
Nanafrocin demonstrates significant in vitro activity against various cell lines. All three cell lines (HCT116 colon, A549 lung, and HL60 bone marrow human tumor cells) are significantly cytotoxically affected by Nanafrocin at concentrations of 10-10,000 nM over 72 hours. In A549 cells, Nanafrocin (0.5, 5 μM; 72 hours) induces the production of the RASSF1A protein. The relative induction at 5 μM is 18-fold. No effect is seen on DNMT1's enzymatic activity. The compound also inhibits the in vitro growth of P. falciparum with an IC80 of 33.1 nM. |
| ln Vivo |
Nanafrocin is active in vivo as a quinone antibiotic. In vivo, the compound is first reduced by flavin or NADH dehydrogenase and then rapidly undergoes auto-oxidation to generate singlet oxygen (O2-). Increased intracellular O2- concentration leads to inhibition of DNA, RNA, and cell wall peptidoglycan synthesis. The compound may have anti-tumor properties through inhibition of DNMT3B and reactivation of the tumor suppressor gene RASSF1A. Specific in vivo efficacy data in tumor models, including doses and routes of administration, are not extensively detailed in the available literature.
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| Enzyme Assay |
In vitro enzyme assays for Nanafrocin involve measuring DNA methyltransferase activity. DNMT3B enzyme is incubated with a DNA substrate containing CpG sites and S-adenosylmethionine (SAM) as the methyl donor. Nanafrocin is added at varying concentrations (typically 0.1-1000 nM), and methylation is quantified by detecting incorporation of radiolabeled methyl groups from [³H]-SAM into the DNA substrate. Reactions are terminated by acidification, and DNA is captured on filters for scintillation counting. IC50 values are calculated from inhibition curves. Control experiments with DNMT1 are performed to confirm selectivity. Enzyme activity is also assessed by methylation-specific PCR or bisulfite sequencing.
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| Cell Assay |
Cytotoxicity assay[1]
Cell Types: HCT116 (colon), A549 (lung) and HL60 (bone marrow) human tumor cell lines Tested Concentrations: 10, 100, 1000, 10000 nM Incubation Duration: 72 hrs (hours) Experimental Results: Obvious cytotoxicity to All three cell lines were affected. Western Blot Analysis[1] Cell Types: A549 Cell Tested Concentrations: 0.5, 5 μM Incubation Duration: 72 hrs (hours) Experimental Results: demonstrated induction of RASSF1A protein expression. RT-PCR[1] Cell Types: A549 Cell Tested Concentrations: 5 μM Incubation Duration: 72 hrs (hours) Experimental Results: Relative induction 18-fold. For in vitro cell-based assays, human cancer cell lines (e.g., HCT116 colon, A549 lung, HL60 bone marrow) are cultured in appropriate medium. Cells are treated with Nanafrocin at concentrations ranging from 10 to 10,000 nM for 72 hours. Cytotoxicity is assessed using MTT, CCK-8, or similar viability assays. RASSF1A protein expression is measured by Western blot analysis in A549 cells treated with 0.5 or 5 μM Nanafrocin for 72 hours. RASSF1A mRNA levels are quantified by RT-PCR (relative induction of 18-fold at 5 μM). DNA methylation status of gene promoters is analyzed by methylation-specific PCR or bisulfite sequencing. |
| Animal Protocol |
In vivo animal studies for Nanafrocin would typically use tumor xenograft models in immunodeficient mice. Human cancer cells (e.g., HCT116, A549) are implanted subcutaneously, and tumors are allowed to establish. Nanafrocin is administered intraperitoneally or intravenously at doses determined from pharmacokinetic and toxicity studies. Tumor volume is measured twice weekly. RASSF1A reactivation and DNA methylation changes are assessed in tumor tissues post-treatment. Survival and body weight are monitored. Specific protocols using Nanafrocin are not extensively documented in the available literature, though the compound has been studied for its anti-tumor and anti-malarial properties.
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| ADME/Pharmacokinetics |
Nanafrocin is a small molecule with molecular formula C16H14O6 and molecular weight 302.28 g/mol. The compound is a quinone antibiotic that undergoes redox cycling in vivo. It is first reduced by flavin or NADH dehydrogenase and then rapidly autooxidized, generating reactive oxygen species. Detailed pharmacokinetic parameters (absorption, distribution, metabolism, excretion, half-life, bioavailability) are not extensively characterized in the available literature. As a quinone antibiotic, its stability and tissue distribution may be influenced by its redox properties.
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| Toxicity/Toxicokinetics |
Nanafrocin is a quinone antibiotic with activity against Gram-positive bacteria, mycoplasmas, and fungi. Its mechanism of action involves reduction by flavin or NADH dehydrogenase followed by auto-oxidation to generate singlet oxygen (O2-), which inhibits DNA, RNA, and cell wall peptidoglycan synthesis. The compound is a selective DNMT3B inhibitor (IC50 = 500 nM) that reactivates silenced tumor suppressor genes in human cancer cells. Nanafrocin inhibits the in vitro growth of P. falciparum (IC80 = 33.1 nM). No approved therapeutic status is reported. Further research is ongoing to explore its potential as an anti-cancer and anti-malarial agent.
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| References |
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| Additional Infomation |
Nanamidine A is a pyranoquinone antibiotic derived from Streptomyces rosa var. notoensis strain OS-3966. It is a bacterial metabolite. It is a benzo[a]chloroquinone compound, belonging to the organic oxygen heterocyclic antibiotic class, and is also a monocarboxylic acid. Nanamidine A has been reported to exist in Streptomyces rosa, Streptomyces roseus, and other organisms with relevant data. Nanamidine A is a quinone antibiotic isolated from Streptomyces rosa var. notoensis, and is active against Gram-positive bacteria, mycoplasma, and fungi. In vivo, nanamidine A is first reduced by flavin or NADH dehydrogenase, and then rapidly undergoes auto-oxidation to generate singlet oxygen (O2-). Increased intracellular O2- concentration leads to inhibition of DNA, RNA, and cell wall peptidoglycan synthesis. In addition, nanamycin A may have anti-tumor properties, the mechanism of which is to reduce DNA methylation levels by inhibiting DNA methyltransferase 3B (DNMT3B) and reactivating the tumor suppressor gene RASSF1A.
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| Molecular Formula |
C16H14O6
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| Molecular Weight |
302.282
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| Exact Mass |
302.079
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| CAS # |
52934-83-5
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| Related CAS # |
Dihydrokalafungin;98392-26-8
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| PubChem CID |
442757
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| Appearance |
Yellow to orange solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
601.5±55.0 °C at 760 mmHg
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| Flash Point |
229.0±25.0 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.649
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| LogP |
2.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
22
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| Complexity |
563
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@H]1C2=C(C[C@@H](O1)CC(=O)O)C(=O)C3=C(C2=O)C(=CC=C3)O
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| InChi Key |
ZCJHPTKRISJQTN-JGVFFNPUSA-N
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| InChi Code |
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
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| Chemical Name |
2-[(1S,3R)-9-hydroxy-1-methyl-5,10-dioxo-3,4-dihydro-1H-benzo[g]isochromen-3-yl]acetic acid
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| Synonyms |
Antibiotic OS 3966A; Nanaomycin A; Nanafrocin
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3082 mL | 16.5410 mL | 33.0819 mL | |
| 5 mM | 0.6616 mL | 3.3082 mL | 6.6164 mL | |
| 10 mM | 0.3308 mL | 1.6541 mL | 3.3082 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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