KU0060648 HCl is a novel, potent and dual inhibitor of DNA-dependent protein kinase (DNA-PK) and PI3Kα/β/δ (Phosphoinositide 3-kinases) with potential antitumor activity. It inhibits DNA-PK and PI3Kα/β/δ with an IC50 of 8.6 nM and 4 nM, 0.5 nM, 0.1 nM respectively. It exhibits 20-1000 fold higher selectivity for DNA-PK over other PIKKs and a panel of 60 other kinases.

Physicochemical Properties

Molecular Formula	C₂₇H₂₉CL₂N₇O₂S
Molecular Weight	586.54
Related CAS #	881375-00-4
Appearance	Typically exists as solid at room temperature
SMILES	O=C(NCC1=CC=C(S(C2=CC(F)=CC(F)=C2)(=O)=O)C=C1)C3=CN4C(C=C3)=NC=C4.Cl
Synonyms	KU-0060648 HCl
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

ln Vitro	In vitro activity : KU-0060648 exhibits differential effects on growth inhibition, but is not profoundly cytotoxic in a panel of human cancer cell lines. It inhibits DNA-PK and PI-3K with greater potency in MCF7 than SW620 cell using cell-based assays. Five-day exposure to 1 mM KU-0060648 inhibits cell proliferation by more than 95% in MCF7 cells but only by 55% in SW620 cells. In clonogenic survival assays, KU-0060648 increases the cytotoxicity of etoposide and doxorubicin across the panel of DNA-PKcs-proficient cells, but not in DNA-PKcs-deficient cells, confirming that enhanced cytotoxicity of the topoisomerase II poisons etoposide and doxorubicin is due to DNA-PK inhibition.
ln Vivo	In mice bearing SW620 and MCF7 xenografts, KU-0060648 concentrations that were sufficient for in vitro growth inhibition and chemosensitization were maintained within the tumor at nontoxic doses for at least 4 hours. KU-0060648 alone delayed the MCF7 xenografts growth and increased etoposide-induced tumor growth delay in both in MCF7 and SW620 xenografts by up to 4.5 folds, without causing etoposide toxicity to unacceptable levels
Animal Protocol	Mice bearing SW620 and MCF7 xenografts
References	Mol Cancer Ther.2012 Aug;11(8):1789-98.

Solubility Data

Solubility (In Vitro)	DMSO: ~10 mM Water: N/A Ethanol: N/A
Solubility (In Vivo)	30% propylene glycol, 5% Tween 80, 65% D5W: 20mg/mL (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.7049 mL	8.5246 mL	17.0491 mL
	5 mM	0.3410 mL	1.7049 mL	3.4098 mL
	10 mM	0.1705 mL	0.8525 mL	1.7049 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.