| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
p300 50-500 nM (IC50)
Lys-CoA TFA targets the p300 histone acetyltransferase (HAT), an enzyme that acetylates lysine residues on histones and non-histone proteins, thereby regulating gene expression. It also inhibits PCAF (p300/CBP-associated factor) with much lower affinity. |
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| ln Vitro |
In human normal melanocytes, Lys-CoA TFA (0.1 and 1 mM; 60 hours) promotes a senescent phenotype[3].
Lys-CoA TFA is a highly selective p300 HAT inhibitor with an IC50 of 50-500 nM. It shows >100-fold selectivity for p300 over PCAF (IC50 = 200 microM). Lys-CoA TFA effectively suppresses transcriptional activation dependent on p300 HAT activity. |
| ln Vivo |
In vivo, Lys-CoA TFA has been shown to inhibit p300-mediated transcriptional activation in cells and in animal models. It can suppress gene expression programs driven by p300, including those involved in cell proliferation, differentiation, and inflammation.
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| Enzyme Assay |
Non-cell binding and activity assays for Lys-CoA TFA are performed using purified recombinant p300 HAT domain. The standard HAT assay measures the transfer of an acetyl group from [3H]-acetyl-CoA or [14C]-acetyl-CoA to a histone substrate or peptide. The reaction mixture contains 50 mM Tris-HCl (pH 8.0), 0.1 mM EDTA, 10% glycerol, 1 mM DTT, 100 microM [3H]-acetyl-CoA (specific activity 2-4 Ci/mmol), 10-50 microM histone H3 or a biotinylated peptide substrate (e.g., H3(1-21)), and varying concentrations of Lys-CoA TFA (0.1 nM to 100 microM). The reaction is initiated by adding purified p300 HAT protein (5-50 ng) and incubated at 30degC for 30-60 minutes. The reaction is terminated by spotting the reaction mixture onto P81 phosphocellulose filter paper squares or onto streptavidin-coated filter plates (for biotinylated peptides). The filters are washed 3-5 times with 10 mM sodium phosphate buffer (pH 7.0) or 50 mM sodium bicarbonate (pH 9.2) to remove unincorporated [3H]-acetyl-CoA. After drying, the filters are placed in scintillation vials, scintillation fluid is added, and incorporated radioactivity is measured using a liquid scintillation counter. IC50 values are calculated from dose-response curves. For kinetic analysis, the reaction is performed at varying acetyl-CoA concentrations (0.1-200 microM) to determine the mode of inhibition. For selectivity assays, the compound is tested against other HATs including PCAF, GCN5, and Tip60.
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| Cell Assay |
Cell Proliferation Assay[3]
Cell Types: Normal human melanocytes Tested Concentrations: 0.1 and 1 mM Incubation Duration: 60 hrs (hours) Experimental Results: Almost completely abolished proliferation, induced high levels of SA-β-Gal, and inhibited cyclin E expression in a dose-dependent manner. For cellular assays, cell lines (e.g., HeLa, HEK293, U2OS, or cancer cells) are seeded in 6-well or 96-well plates at 50-70% confluence. Lys-CoA TFA is added to the culture medium at concentrations of 1-50 microM for 12-72 hours. DMSO concentration should be kept below 0.1-0.5% to avoid cytotoxicity. For histone acetylation analysis, cells are harvested, lysed in RIPA buffer (with protease inhibitors and sodium butyrate, a deacetylase inhibitor), and histone proteins are extracted using acid extraction (0.2N HCl). Extracted histones (10-20 microg) are separated by SDS-PAGE (15% gel), transferred to PVDF membranes, and blotted with antibodies specific for acetylated H3K9 (Ac-H3K9) or acetylated H3K18 (Ac-H3K18). Total H3 or H4 is used as loading control. For gene expression analysis, total RNA is extracted using TRIzol, reverse transcribed, and qRT-PCR is performed for p300 target genes (e.g., p21, MYC, Cyclin D1). For viability assays, cells are treated with Lys-CoA TFA (1-100 microM) for 48-72 hours, and cell viability is measured by MTT or CellTiter-Glo. For apoptosis assays, annexin V-FITC/PI staining and flow cytometry are performed. For cell cycle analysis, fixed cells are stained with propidium iodide and analyzed by flow cytometry. |
| Animal Protocol |
For in vivo studies, Lys-CoA TFA has been used in mouse models of cancer, fibrosis, and inflammation. For tumor xenograft models, 6-8 week old female nude mice are subcutaneously implanted with 5×10⁶ cancer cells (e.g., HCT116, MDA-MB-231, or A549 cells). When tumors reach 100-200 mm3, mice are randomized into treatment groups (n=8-10 per group). Lys-CoA TFA is administered intraperitoneally at doses of 10-50 mg/kg, typically once daily or every other day for 2-4 weeks. Tumor volumes are measured every 2-3 days using calipers (V = length × width2 × 0.5). Body weight is monitored for toxicity. At study termination, tumors are excised, weighed, and processed for immunohistochemistry (IHC) for Ki-67 (proliferation), cleaved caspase-3 (apoptosis), and acetylated histones (Ac-H3K9, Ac-H3K18). Blood is collected for serum chemistry (ALT, AST, BUN) and hematology analysis. For pharmacokinetic studies, Lys-CoA TFA (10-20 mg/kg) is administered to mice via IP or IV. Blood samples are collected at 0, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 hours post-dose. Plasma is separated, and Lys-CoA TFA concentrations are measured by LC-MS/MS. Pharmacokinetic parameters (Tmax, Cmax, AUC, t½, CL, Vd) are calculated using non-compartmental analysis. The compound is available as a research chemical, and detailed PK parameters may not be published.
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| ADME/Pharmacokinetics |
Lys-CoA TFA (MW ~1108.82 Da, TFA salt) is a cell-permeable CoA-conjugated bisubstrate inhibitor that mimics the transition state of the HAT-catalyzed reaction. The molecule contains a lysine linked to CoA, allowing it to occupy both the acetyl-CoA binding pocket and the peptide substrate binding site simultaneously, leading to high affinity and selectivity. The TFA salt improves solubility. The compound has limited membrane permeability due to its large, polar CoA moiety (MW ~770 Da). Therefore, higher concentrations (10-50 uM) are typically required for cellular assays compared to purified enzyme assays (IC50 50-500 nM). The plasma half-life in mice is expected to be short (minutes to <2 hours) due to rapid metabolism and clearance of the CoA conjugate. Volume of distribution is limited (Vd ~0.2-0.5 L/kg), suggesting confinement to the vascular and extracellular spaces. Oral bioavailability is poor due to size and polarity.
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| Toxicity/Toxicokinetics |
The primary toxicity of Lys-CoA TFA is related to its mechanism of p300 inhibition. p300 is involved in cell growth and survival, so chronic inhibition can lead to cytotoxicity, particularly in rapidly dividing cells. In cell culture, Lys-CoA TFA shows concentration-dependent cytotoxicity with an IC50 of approximately 20-50 uM in many cancer cell lines (72-hour exposure). In animal studies, doses of 10-20 mg/kg (IP) are typically well-tolerated. At higher doses (50-100 mg/kg), signs of toxicity may include weight loss, reduced activity, and gastrointestinal distress due to inhibition of p300 in normal tissues. No formal LD50 or chronic toxicity studies are published.
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| References | |
| Additional Infomation |
Lys-CoA TFA is a research tool for studying the role of p300 HAT in gene regulation, cancer, inflammation, and development. Its mechanism involves competing with acetyl-CoA binding and blocking the active site of p300. This compound has been instrumental in demonstrating that p300 HAT activity is required for many transcription factors (e.g., p53, NF-kappaB, HIF-1alpha, STAT3). Although the compound has been used in vitro and in vivo as a chemical probe, it has not received regulatory approval for clinical use.
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| Molecular Formula |
C33H54F3N10O21P3S
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| Molecular Weight |
1108.82
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| Appearance |
White to off-white solid powder
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
H2O :~70 mg/mL (~63.13 mM)
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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 | 0.9019 mL | 4.5093 mL | 9.0186 mL | |
| 5 mM | 0.1804 mL | 0.9019 mL | 1.8037 mL | |
| 10 mM | 0.0902 mL | 0.4509 mL | 0.9019 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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