DCH36_06 is a potent and specific p300/CBP inhibitor (antagonist) with IC50s of 0.6 μM and 3.2 μM for p300 and CBP, respectively. DCH36_06-mediated inhibition of p300/CBP leads to hypoacetylation of H3K18 in leukemia cells. anti-tumor effects.

Physicochemical Properties

Molecular Formula	C18H13CLN2O3S
Molecular Weight	372.825422048569
Exact Mass	372.033
CAS #	593273-05-3
PubChem CID	1797299
Appearance	Orange to red solid powder
LogP	4
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	3
Heavy Atom Count	25
Complexity	634
Defined Atom Stereocenter Count	0
SMILES	ClC1=C(C)C=CC(=C1)N1C(NC(/C(=C\C=C\C2=CC=CO2)/C1=O)=O)=S
InChi Key	AYNCXNUUERDREH-FMDPHQNASA-N
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+
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
Synonyms	DCH36-06; DCH36 06; DCH36_06
HS Tariff Code	2934.99.9001
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)

Biological Activity

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].
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].
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.
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 .
References	[1]. Discovery and biological evaluation of thiobarbituric derivatives as potent p300/CBP inhibitors. Bioorg Med Chem. 2018 Nov 1;26(20):5397-5407.

Solubility Data

Solubility (In Vitro)

DMSO : ~125 mg/mL (~335.27 mM)

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.