| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Targets |
TH1834 targets Tip60 (KAT5), a histone acetyltransferase that plays a critical role in DNA damage repair, transcription, and apoptosis. By inhibiting Tip60, TH1834 prevents the acetylation of histones and non-histone proteins involved in DNA repair pathways, leading to accumulation of DNA damage. This inhibition specifically affects breast cancer cells and does not affect the related histone acetyltransferase MOF. The compound's selectivity for Tip60 over MOF suggests a targeted mechanism of action.
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| ln Vitro |
MCF7 cells treated with TH1834 dihydrochloride (0-500 μM; 1 hour) exhibit a significant reduction in viability [1]. MCF7 cell viability is dramatically decreased by TH1834 dihydrochloride (0-500 μM; 1 hour; MCF7 cells) treatment [1]. MCF7 cells are treated with 500 μM TH1834 dihydrochloride for one hour, which causes caspase 3 activation [1]. When cells treated with TH1834 dihydrochloride, Tip60 activity increases the number of cancer cells and causes unrepaired DNA damage in breast cancer [1].
TH1834 demonstrates potent in vitro activity against breast cancer cells. MCF7 cells treated with TH1834 dihydrochloride at concentrations of 0-500 μM for 1 hour exhibit a significant reduction in viability. Cell viability is dramatically decreased at all concentrations tested. Treatment with 500 μM TH1834 dihydrochloride for one hour causes caspase 3 activation. When cells are treated with TH1834 dihydrochloride, Tip60 inhibition increases the number of cancer cells with unrepaired DNA damage. Cytotoxicity is dramatically increased at all concentrations used. |
| ln Vivo |
In vivo activity of TH1834 is not extensively detailed in the available literature. Based on its mechanism as a Tip60 inhibitor, the compound would be expected to show anti-tumor activity in breast cancer models. The induction of apoptosis and DNA damage in breast cancer cells suggests potential for in vivo efficacy. Specific in vivo efficacy data, including tumor xenograft studies, dosing regimens, and routes of administration, are not provided in the available references. Further research is needed to evaluate its therapeutic potential in vivo.
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| Enzyme Assay |
In vitro enzyme assays for TH1834 involve measuring Tip60 (KAT5) histone acetyltransferase activity. Recombinant Tip60 enzyme is incubated with histone substrates (e.g., histone H4 or histone H3) and acetyl-CoA in the presence of varying concentrations of TH1834 (typically 0.1-500 μM). The reaction is initiated by addition of enzyme and terminated by acidification or addition of stop solution. Histone acetylation is quantified by Western blot using anti-acetylated histone antibodies, by ELISA, or by radiometric assays using [³H]-acetyl-CoA. IC50 values are calculated from concentration-response curves. Control experiments with MOF enzyme are performed to confirm selectivity.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: MCF7 cells Tested Concentrations: 0 μM, 0.5 μM, 5 μM, 50 μM and 500 μM Incubation Duration: 1 hour Experimental Results: Dramatically diminished the viability of MCF7 cells. Cytotoxicity assay[1] Cell Types: MCF7 Cell Tested Concentrations: 0 μM, 0.5 μM, 5 μM, 50 μM and 500 μM Incubation Duration: 1 hour Experimental Results: Cytotoxicity increased Dramatically at all concentrations used. Western Blot Analysis[1] Cell Types: MCF7 Cells Tested Concentrations: 500 μM Incubation Duration: 1 hour Experimental Results: In an independent assay, significant caspase 3 activation was observed in MCF7 cells. For in vitro cell-based assays, MCF7 breast cancer cells are cultured in appropriate medium. Cells are treated with TH1834 dihydrochloride at concentrations of 0, 0.5, 5, 50, and 500 μM for 1 hour. Cell viability is assessed using MTT, CCK-8, or similar assays. Cytotoxicity is measured using LDH release assays. Caspase 3 activation is detected by Western blot analysis using anti-caspase 3 antibodies or by fluorogenic substrate assays. DNA damage is assessed by γ-H2AX staining or comet assays. Tip60 activity in treated cells can be measured by immunoprecipitation and histone acetylation assays. |
| Animal Protocol |
In vivo animal studies for TH1834 would typically use breast cancer xenograft models in immunodeficient mice. MCF7 or other breast cancer cells are implanted subcutaneously, and tumors are allowed to establish. TH1834 is administered intraperitoneally or intravenously at doses determined from pharmacokinetic and toxicity studies. Tumor volume is measured twice weekly. Apoptosis and DNA damage are assessed in tumor tissues by TUNEL staining and γ-H2AX immunohistochemistry. Survival and body weight are monitored. Specific protocols using TH1834 are not extensively documented in the available literature.
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| ADME/Pharmacokinetics |
TH1834 hydrochloride has a molecular formula of C33H42Cl2N6O3 and molecular weight of 641.63. The compound should be stored as a powder at -20°C for up to 3 years and in solvent at -80°C for up to 1 year. Detailed solubility and pharmacokinetic parameters (absorption, distribution, metabolism, excretion, half-life, bioavailability) are not extensively characterized in the available literature. As a small molecule inhibitor, it would be expected to be suitable for in vivo administration if formulated appropriately.
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| Toxicity/Toxicokinetics |
Specific toxicity data for TH1834 are not extensively detailed in the available literature. As a Tip60 inhibitor, its toxicity profile would be related to inhibition of histone acetylation and DNA repair pathways. The compound's selectivity for Tip60 over MOF may reduce off-target effects. In cell-based assays, concentrations up to 500 μM for 1 hour are used, with significant cytotoxicity observed. Standard toxicology assessments would be required for therapeutic development, including acute, subchronic, and chronic toxicity studies, as well as genotoxicity and reproductive toxicity evaluations.
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| References | |
| Additional Infomation |
TH1834 HCl is a specific Tip60 (KAT5) histone acetyltransferase inhibitor. It induces apoptosis and enhances DNA damage in breast cancer cells, specifically MCF7 cells. TH1834 does not affect the activity of the related histone acetyltransferase MOF. Treatment with TH1834 leads to a significant reduction in cell viability and a highly significant increase in cytotoxicity. The compound causes caspase 3 activation and unrepaired DNA damage in breast cancer cells. No approved therapeutic status is reported. Further research is needed to evaluate its in vivo efficacy and safety profile.
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| Molecular Formula |
C33H42CL2N6O3
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| Molecular Weight |
641.630985736847
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| Exact Mass |
640.269
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| CAS # |
2108830-09-5
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| Related CAS # |
TH1834;2108830-08-4
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| PubChem CID |
91826511
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
16
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| Heavy Atom Count |
44
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| Complexity |
761
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.Cl.O(C1C=CC(=CC=1)CN1CCCC1)CCCCN(CC1C=CC(C2N=NN(CC(=O)O)N=2)=CC=1)CCC1C=CC=CC=1
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| InChi Key |
HYXIFSOROZPMMU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C33H40N6O3.2ClH/c40-32(41)26-39-35-33(34-36-39)30-14-10-28(11-15-30)25-38(22-18-27-8-2-1-3-9-27)21-6-7-23-42-31-16-12-29(13-17-31)24-37-19-4-5-20-37;;/h1-3,8-17H,4-7,18-26H2,(H,40,41);2*1H
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| Chemical Name |
2-[5-[4-[[2-phenylethyl-[4-[4-(pyrrolidin-1-ylmethyl)phenoxy]butyl]amino]methyl]phenyl]tetrazol-2-yl]acetic acid;dihydrochloride
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| Synonyms |
TH 1834 HCl; TH-1834 HCl; TH1834 HCl
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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 : ~100 mg/mL (~155.85 mM)
DMSO : ≥ 100 mg/mL (~155.85 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.24 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.24 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.24 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 25 mg/mL (38.96 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5585 mL | 7.7927 mL | 15.5853 mL | |
| 5 mM | 0.3117 mL | 1.5585 mL | 3.1171 mL | |
| 10 mM | 0.1559 mL | 0.7793 mL | 1.5585 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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