SML1257

KU-0060648

≥98% (HPLC)

• Synonym(s): 4-Ethyl-N-[4-[2-(4-morpholinyl)-4-oxo-4H-1-benzopyran-8-yl]-1-dibenzothienyl]-1-piperazineacetamide, KU 0060648
• Empirical Formula (Hill Notation): C₃₃H₃₄N₄O₄S
• CAS Number: 881375-00-4
• Molecular Weight: 582.71
• MDL number: MFCD17214218
• UNSPSC Code: 12352200
• PubChem Substance ID: 329825749
• NACRES: NA.77

Properties

• Quality Level: 100
• Assay: ≥98% (HPLC)
• form: powder
• color: white to light brown
• solubility: DMSO: 1 mg/mL, clear (warmed)
• storage temp.: −20°C
• SMILES string: O=C(CN1CCN(CC)CC1)NC2=CC=C(C3=CC=CC4=C3OC(N5CCOCC5)=CC4=O)C6=C2C(C=CC=C7)=C7S6
• InChI: 1S/C33H34N4O4S/c1-2-35-12-14-36(15-13-35)21-29(39)34-26-11-10-23(33-31(26)25-6-3-4-9-28(25)42-33)22-7-5-8-24-27(38)20-30(41-32(22)24)37-16-18-40-19-17-37/h3-11,20H,2,12-19,21H2,1H3,(H,34,39)
• InChI key: AATCBLYHOUOCTO-UHFFFAOYSA-N

Description

Biochem/physiol Actions

KU-0060648 is a very potent dual inhibitor of DNA-PK and PI3K. The IC₅₀ values for inhibition of DNA-PK in MCF7 and SW620 cells are 19 and 170 nM, respectively. The compound KU-0060648 inhibits MCF7 PI3K activity with an IC₅₀ of 39 nM, but is inactive against PI3K in SW620, suggesting a cell-dependent mechanism of inhibition. KU-0060648 increases sensitivity to DNA damaging cytotoxic drugs such as etoposide and doxorubicin in tumor cell lines expressing DNA-PK. KU-0060648 stimulates Cas9 (CRISPR associated protein 9) mediated genome editing by enhancing the rate of homology directed-repair (HDR) and decreasing the rate of NHEJ (non-homologous end-joining).

KU-0060648 is observed to inhibit proliferation and initiate apoptosis in hepatocellular carcinoma. KU-0060648 is useful in chemotherapy as it increases the efficiency of double stranded breaks initiated by anticancer drugs.

Safety Information

• Pictograms: GHS06
• Signal Word: Danger
• Hazard Statements: H301
• Precautionary Statements: P264 - P270 - P301 + P310 - P405 - P501
• Hazard Classifications: Acute Tox. 3 Oral
• Storage Class Code: 6.1C - Combustible acute toxic Cat.3 / toxic compounds or compounds which causing chronic effects
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable