DK1 (also known as DNA-PK-IN-8) is a DNA-dependent protein kinase (DNA-PK) inhibitor with anticancer activity. DK1 showed high DNA-PK-inhibitory potency (IC50 = 0.8 nM), slightly better than that of AZD-7648 (IC50 = 1.58 nM). Mode of action studies revealed that compound DK1 decreased the expression levels of γH2A.X and demonstrated synergistic antiproliferative activity against a series of cancer cell lines when used in combination with doxorubicin. Moreover, DK1 showed reasonable in vitro drug-like properties and favorable in vivo pharmacokinetics as an oral drug candidate. Importantly, the combination therapy of DK1 with DNA double-strand break (DSB)-inducing agent doxorubicin showed synergistic anticancer efficacy in the HL-60 xenograft model with a tumor growth inhibition (TGI) of 52.4% and 62.4% for tumor weight and tumor volume, respectively. In conclusion, DK1 is a novel DNA-PK inhibitor with great promise for further study.

Physicochemical Properties

Molecular Formula	C19H22N8O2
Molecular Weight	394.43
Appearance	Off-white to yellow solid powder
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
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

References

Discovery of novel 7,8-dihydropteridine-6(5H)-one-based DNA-PK inhibitors as potential anticancer agents via scaffold hopping strategy. Eur J Med Chem. 2022;237:114401

Solubility Data

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

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.31 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5353 mL	12.6765 mL	25.3530 mL
	5 mM	0.5071 mL	2.5353 mL	5.0706 mL
	10 mM	0.2535 mL	1.2677 mL	2.5353 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.