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| 1mg |
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| 10mg |
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| Targets |
Histone acetyltransferases p300 and CBP (CREB-binding protein). DCH36_06 inhibits both p300 and CBP with IC50 values of 0.6 μM and 3.2 μM, respectively. These enzymes play crucial roles in gene regulation through histone acetylation, and their inhibition leads to epigenetic modifications that affect cancer cell proliferation.
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| ln Vitro |
Leukemic cells undergo dose-dependent apoptosis and cell cycle arrest in the G1 phase upon treatment with DCH36_06 (6.7–20 μM; 24-48 hours) [1]. The cleavage of pro-caspase 3, pro-caspase 9, and PARP1 is dramatically activated in a dose-dependent manner upon treatment with DCH36_06 (5-10 μM; 24 hours) [1]. When tested against the leukemia cell lines CEM, MOLT3, MOLT4, Jurkat, MV4-11, THP-1, RS4;11, KOPN8, Kasumi-1, and K562 cells, DCH36_06 shown strong antiproliferative activity in a dose-dependent manner; its IC50 values are in the single-digit micromolar range [1].
DCH36_06 demonstrates potent anti-proliferative activity in several leukemia cell lines. The compound mediated p300/CBP inhibition leads to hypoacetylation on H3K18 in leukemic cells. In vitro studies show that DCH36_06 arrests the cell cycle at G1 phase and induces apoptosis through activation of caspase-3, caspase-9, and PARP, elucidating the molecular mechanism of its anti-proliferative activity. |
| ln Vivo |
DCH36_06 inhibits the growth of mouse leukemia xenografts when administered intraperitoneally (i.p.) at 25–50 mg/kg for 20 days [1].
DCH36_06 exhibits anti-tumor activity in leukemia xenograft models. In vivo studies demonstrate that p300/CBP inhibition by DCH36_06 slows the proliferation of several leukemia cell lines and induces apoptosis. The compound has shown potent anti-proliferation as well as anti-tumor activity in in vivo leukemia models. |
| Enzyme Assay |
In vitro enzyme inhibition assays are performed using purified recombinant p300 and CBP enzymes. The assay typically measures the transfer of acetyl groups from 14C-acetyl-CoA or 3H-acetyl-CoA to histone substrates or peptide substrates. DCH36_06 is incubated with the enzyme and substrate at varying concentrations, and the enzymatic activity is quantified by measuring incorporated radioactivity or using fluorescence-based detection methods. IC50 values are calculated from dose-response curves.
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| Cell Assay |
Cell cycle analysis[1]
Cell Types: MV4-11 Cell Tested Concentrations: 6.7 μM, 20 μM Incubation Duration: 24 hrs (hours), 48 hrs (hours) Experimental Results: Dose-dependent cell cycle arrest in G1 phase. Apoptosis analysis [1] Cell Types: MV4-11 Cell Tested Concentrations: 6.7 μM, 20 μM Incubation Duration: 24 hrs (hours), 48 hrs (hours) Experimental Results: Significant induction of apoptosis. Western Blot Analysis [1] Cell Types: MV4-11 cells Tested Concentrations: 5 μM, 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Significant activation of pro-caspase 3, pro-caspase 9 and cleavage of PARP1 in a dose-dependent manner. Cellular assays are conducted using leukemia cell lines such as HL-60, MV4-11, or other p300/CBP-dependent cancer cell lines. Cells are treated with DCH36_06 at concentrations ranging from 0 to 20 μM for 24-48 hours. Cell proliferation is assessed using MTT, CCK-8, or cell counting assays. Cell cycle analysis is performed by flow cytometry following propidium iodide staining, and apoptosis is evaluated using Annexin V-FITC/PI double staining or by measuring caspase-3/9 and PARP cleavage by Western blot. |
| Animal Protocol |
Animal/Disease Models: MV4-11 xenograft nude mice [1]
Doses: 25 mg/kg, 50 mg/kg Route of Administration: intraperitoneal (ip) injection; every two days; 20 days Experimental Results: Tumor growth rate was Dramatically diminished in a dose-dependent manner . In vivo efficacy studies are typically performed using immunodeficient mice bearing subcutaneous leukemia xenografts. DCH36_06 is administered via intraperitoneal or intravenous injection at various doses, and tumor volume is measured every 2-3 days using calipers. At the end of the study, tumors are excised and analyzed for H3K18 acetylation levels by Western blot or immunohistochemistry to confirm target engagement. Body weight and general health of animals are monitored throughout the study. |
| ADME/Pharmacokinetics |
The compound has a molecular weight of 372.83 g/mol and molecular formula C18H13ClN2O3S. DCH36_06 is soluble in DMSO (125 mg/mL with ultrasonic assistance) and should be stored at 4°C protected from light. Stock solutions should be aliquoted and stored in tightly sealed vials for up to 1 month, with repeated freeze-thaw cycles avoided.
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| Toxicity/Toxicokinetics |
Toxicological data for DCH36_06 are primarily derived from in vitro cell viability assays and in vivo xenograft studies. At effective anti-proliferative concentrations (6.7-20 μM), the compound induces apoptosis in leukemic cells. Standard safety precautions should be followed when handling this compound, as with all small-molecule inhibitors. No specific acute toxicity data have been reported in the literature.
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| References | |
| Additional Infomation |
DCH36_06 is a research-use only compound and has not yet entered clinical trials. It is a bona fide potent p300/CBP inhibitor with IC50 values of 0.6 μM for p300 and 3.2 μM for CBP. The compound represents a valuable tool for studying the role of p300/CBP-mediated histone acetylation in cancer biology and for validating histone acetyltransferases as therapeutic targets in leukemia. Its mechanism of action involves inhibition of histone acetylation, leading to altered gene expression and apoptosis.
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| Molecular Formula |
C18H13CLN2O3S
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| Molecular Weight |
372.825422048569
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| Exact Mass |
372.033
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| CAS # |
593273-05-3
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| PubChem CID |
1797299
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| Appearance |
Orange to red solid powder
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| LogP |
4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
25
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| Complexity |
634
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=C(C)C=CC(=C1)N1C(NC(/C(=C\C=C\C2=CC=CO2)/C1=O)=O)=S
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| InChi Key |
AYNCXNUUERDREH-FMDPHQNASA-N
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| InChi Code |
InChI=1S/C18H13ClN2O3S/c1-11-7-8-12(10-15(11)19)21-17(23)14(16(22)20-18(21)25)6-2-4-13-5-3-9-24-13/h2-10H,1H3,(H,20,22,25)/b4-2+,14-6+
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| Chemical Name |
(5E)-1-(3-chloro-4-methylphenyl)-5-[(E)-3-(furan-2-yl)prop-2-enylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione
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| Synonyms |
DCH36-06; DCH36 06; DCH36_06
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
DMSO : ~125 mg/mL (~335.27 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.58 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 (5.58 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6822 mL | 13.4109 mL | 26.8219 mL | |
| 5 mM | 0.5364 mL | 2.6822 mL | 5.3644 mL | |
| 10 mM | 0.2682 mL | 1.3411 mL | 2.6822 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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