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SML1257

Sigma-Aldrich

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

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About This Item

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

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

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.

Pictograms

Skull and crossbones
GHS06

Signal Word

Danger

Hazard Statements

H301

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

Certificates of Analysis (COA)

Search for Certificates of Analysis (COA) by entering the products Lot/Batch Number. Lot and Batch Numbers can be found on a product’s label following the words ‘Lot’ or ‘Batch’.

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Developments of DNA-dependent protein kinase inhibitors as anticancer agents.
Ma C C, et al.
Mini-Reviews in Medicinal Chemistry, 14(11), 884-895 (2014)
KU-0060648 inhibits hepatocellular carcinoma cells through DNA-PKcs-dependent and DNA-PKcs-independent mechanisms.
Chen M B, et al.
Oncotarget, 7(13), 17047-17047 (2016)
Joanne M Munck et al.
Molecular cancer therapeutics, 11(8), 1789-1798 (2012-05-12)
DNA double-strand breaks (DSB) are the most cytotoxic lesions induced by topoisomerase II poisons. Nonhomologous end joining (NHEJ) is a major pathway for DSB repair and requires DNA-dependent protein kinase (DNA-PK) activity. DNA-PK catalytic subunit (DNA-PKcs) is structurally similar to
Valentina Perini et al.
International journal of molecular sciences, 21(21) (2020-11-11)
Poly(ADP-ribosyl)polymerase (PARP) synthesizes poly(ADP-ribose) (PAR), which is anchored to proteins. PAR facilitates multiprotein complexes' assembly. Nuclear PAR affects chromatin's structure and functions, including transcriptional regulation. In response to stress, particularly genotoxic stress, PARP activation facilitates DNA damage repair. The PARP
Francis Robert et al.
Genome medicine, 7, 93-93 (2015-08-27)
The ability to modify the genome of any cell at a precise location has drastically improved with the recent discovery and implementation of CRISPR/Cas9 editing technology. However, the capacity to introduce specific directed changes at given loci is hampered by

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