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| Targets |
Trapoxin A is a potent and essentially irreversible inhibitor of histone deacetylases (HDACs), particularly class I HDACs including HDAC11. The compound contains an epoxide group that reacts covalently with the active site of HDAC enzymes, leading to irreversible inhibition. By inhibiting HDACs, trapoxin A prevents the removal of acetyl groups from lysine residues on histone proteins, leading to increased histone acetylation. This affects chromatin structure and gene expression, as acetylated histones are associated with transcriptionally active chromatin. Trapoxin A increases the level of chromatin acetylation associated with histone H3 at low nanomolar concentrations.
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| ln Vitro |
Trapoxin A is a potent histone deacetylase (HDAC) inhibitor with potential anticancer activity. It increases the level of chromatin acetylation associated with histone H3 at low nanomolar concentrations. The compound is an irreversible inhibitor of class I histone deacetylases (HDACs). Trapoxin A induces morphological reversion from sis-transformed NIH3T3 fibroblasts to normal morphology. It inhibits HDAC11.
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| ln Vivo |
In vivo, trapoxin A has been studied for its potential anticancer activity due to its HDAC inhibitory properties. HDAC inhibitors have been shown to induce differentiation, cell cycle arrest, and apoptosis in cancer cells. Trapoxin A's irreversible inhibition of HDACs may provide sustained biological activity. However, the compound's epoxide group may also pose challenges for in vivo use due to potential reactivity. Trapoxin A is primarily a research tool for studying histone acetylation and HDAC function rather than a therapeutic agent.
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| Enzyme Assay |
HDAC enzymatic activity assays are performed using recombinant HDAC enzymes (class I HDACs) and fluorogenic peptide substrates. The substrate contains an acetylated lysine residue, and deacetylation by HDAC produces a product that can be detected by fluorescence after treatment with developer solution. Trapoxin A is incubated with the enzyme and substrate in assay buffer for 30-60 minutes at 37°C. The reaction is stopped and product formation is quantified by fluorescence. IC50 values are calculated from concentration-response curves. The irreversible nature of inhibition is confirmed by pre-incubation experiments where the compound is incubated with the enzyme before substrate addition.
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| Cell Assay |
Cellular assays for HDAC inhibition typically employ cancer cell lines such as HeLa, NIH3T3, or other appropriate cells. Cells are treated with varying concentrations of trapoxin A (typically 1-100 nM) for 6-24 hours. Histone acetylation is assessed by Western blot using antibodies specific for acetylated histone H3 (Ac-H3) or acetylated histone H4 (Ac-H4). Gene expression changes are analyzed by qPCR or RNA-seq. Cell proliferation is assessed by MTT or CellTiter-Glo assays. Apoptosis is evaluated by Annexin V/PI staining. The morphological reversion of sis-transformed NIH3T3 cells is assessed by microscopy.
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| Animal Protocol |
In vivo studies with trapoxin A are typically performed in mouse models of cancer. The compound may be administered via intraperitoneal or intravenous injection. Tumor growth inhibition is assessed in xenograft models. Histone acetylation in tumor tissues is confirmed by immunohistochemistry or Western blot. However, the compound's epoxide group may limit its utility for in vivo studies due to potential reactivity and toxicity. Trapoxin A is primarily a research tool for in vitro studies.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for trapoxin A are limited as it is a research compound. The compound is a cyclic tetrapeptide with an epoxide group that is essential for its irreversible HDAC inhibitory activity. The epoxide group may be reactive and could be metabolized or eliminated rapidly in vivo. Trapoxin A is soluble in DMSO and other organic solvents. It should be stored at -20°C for long-term stability. The compound's cyclic peptide structure may limit oral bioavailability.
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| Toxicity/Toxicokinetics |
Toxicological data for trapoxin A are limited as it is a research compound. As an irreversible HDAC inhibitor, potential toxicities may include effects on normal cell proliferation and differentiation, as well as teratogenic effects. The epoxide group may also pose reactivity concerns. The compound should be handled with appropriate laboratory safety precautions. In cell culture, trapoxin A is typically used at nanomolar concentrations, which are generally well-tolerated in short-term experiments.
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| Additional Infomation |
Trapoxin A is a homocyclic tetrapeptide composed of L-phenylalanyl(x2), D-piperidinyl, and L-2-amino-8-oxo-9,10-epoxydecyl residues. It possesses multiple functions, including as an EC 3.5.1.98 (histone deacetylase) inhibitor, an antitumor drug, and a fungal metabolite. It is a homocyclic peptide containing an epoxide and a ketone. Trapoxin A has been reported in Helicoma ambiens, with relevant data available. Trapoxin is a cyclic tetrapeptide containing an epoxide and exhibits antitumor activity. It is an irreversible inhibitor of histone deacetylases.
Trapoxin A is a microbial cyclic tetrapeptide isolated from Helicoma ambiens. It is a potent histone deacetylase (HDAC) inhibitor with potential anticancer activity. The compound is an irreversible inhibitor of class I histone deacetylases (HDACs). Trapoxin A is used as a research tool to study histone acetylation, chromatin remodeling, and gene expression regulation. The compound contains a unique epoxide group essential for its irreversible inhibition of HDACs. |
| Molecular Formula |
C34H42N4O6
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|---|---|
| Molecular Weight |
602.72048
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| Exact Mass |
602.31
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| CAS # |
133155-89-2
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| PubChem CID |
121875
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3.163
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
44
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| Complexity |
1020
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| Defined Atom Stereocenter Count |
5
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| SMILES |
C1C=CC(CC2NC(=O)C(CCCCCC(C3CO3)=O)NC(=O)C3CCCCN3C(=O)C(CC3C=CC=CC=3)NC2=O)=CC=1
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| InChi Key |
GXVXXETYXSPSOA-UFEOFEBPSA-N
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| InChi Code |
InChI=1S/C34H42N4O6/c39-29(30-22-44-30)18-9-3-8-16-25-31(40)36-26(20-23-12-4-1-5-13-23)32(41)37-27(21-24-14-6-2-7-15-24)34(43)38-19-11-10-17-28(38)33(42)35-25/h1-2,4-7,12-15,25-28,30H,3,8-11,16-22H2,(H,35,42)(H,36,40)(H,37,41)/t25-,26-,27-,28+,30-/m0/s1
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| Chemical Name |
(3S,6S,9S,12R)-3,6-dibenzyl-9-[6-[(2S)-oxiran-2-yl]-6-oxohexyl]-1,4,7,10-tetrazabicyclo[10.4.0]hexadecane-2,5,8,11-tetrone
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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 | 1.6591 mL | 8.2957 mL | 16.5915 mL | |
| 5 mM | 0.3318 mL | 1.6591 mL | 3.3183 mL | |
| 10 mM | 0.1659 mL | 0.8296 mL | 1.6591 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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