881375-00-4

881375-00-4 structure

Name: KU-0060648
Chemical Name: 1-Piperazineacetamide, 4-ethyl-N-[4-[2-(4-morpholinyl)-4-oxo-4H-1-benzopyran-8-yl]-1-dibenzothienyl]
CAS Number: 881375-00-4
Molecular Formula: C₃₃H₃₄N₄O₄S
Molecular Weight: 582.713
Catalog: Biochemical Inhibitor DNA damage DNA-PK inhibitor
Create Date: 2017-11-20 03:14:22
Modify Date: 2024-01-14 11:41:47
KU-0060648 is a dual inhibitor of PI3K and DNA-PK with IC50s of 4 nM, 0.5 nM, 0.1 nM, 0.594 nM and 8.6 nM for PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ and DNA-PK, respectively[1].

Name	1-Piperazineacetamide, 4-ethyl-N-[4-[2-(4-morpholinyl)-4-oxo-4H-1-benzopyran-8-yl]-1-dibenzothienyl]
Synonyms	2-(4-Ethyl-1-piperazinyl)-N-{4-[2-(4-morpholinyl)-4-oxo-4H-chromen-8-yl]dibenzo[b,d]thiophen-1-yl}acetamide 1-Piperazineacetamide, 4-ethyl-N-[4-[2-(4-morpholinyl)-4-oxo-4H-1-benzopyran-8-yl]dibenzo[b,d]thien-1-yl]- KU 0060648

Description	KU-0060648 is a dual inhibitor of PI3K and DNA-PK with IC50s of 4 nM, 0.5 nM, 0.1 nM, 0.594 nM and 8.6 nM for PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ and DNA-PK, respectively[1].
Related Catalog	Signaling Pathways >> PI3K/Akt/mTOR >> mTOR Research Areas >> Cancer Signaling Pathways >> Cell Cycle/DNA Damage >> DNA-PK Signaling Pathways >> PI3K/Akt/mTOR >> PI3K Signaling Pathways >> PI3K/Akt/mTOR >> DNA-PK
Target	PI3Kα:4 nM (IC50) PI3Kβ:0.5 nM (IC50) PI3Kγ:0.594 μM (IC50) PI3Kδ:0.1 nM (IC50) DNA-PK:8.6 nM (IC50)
In Vitro	KU-0060648 inhibits cellular DNA-PK auto-phosphorylation with IC50 values of 0.019 μM (MCF7 cells) and 0.17 μM (SW620 cells), and PI-3K-mediated AKT phosphorylation with IC50 values of 0.039 μM (MCF7 cells) and >10 μM (SW620 cells)[1]. KU-0060648 (30-500 nM; 72 hours) dose-dependently inhibits HepG2 cell proliferation, IC50=134.32nM[2]. KU-0060648 (0.1-1 μM；5 days) inhibits cell lines growth with GI50s of 0.95 μM, 0.21 μM, 0.27 μM, 0.41 μM and 1 μM in SW620, LoVo, MCF7, T47D and MDA-MB-231 cells[1]. KU-0060648 (100-300 nM;12 hours) significantly inhibits activation of PI3K (p85 phosphorylation), AKT (Ser-473 and Thr-308 phosphorylations) and mTOR (p70S6K1 Thr-389 phosphorylation) in HepG2/Huh-7 lines and primary human HCC cells[2]. Cell Proliferation Assay[1] Cell Line: Human breast (MCF7, T47D and MDA-MB-231) and colon (LoVo and SW620) cancer cells Concentration: 0.1-1 μM Incubation Time: 5 days Result: Resulted in> 50% inhibition of cell growth in all cell lines. Western Blot Analysis[2] Cell Line: HCC cells; HepG2/Huh-7 cells Concentration: 100-300 nM Incubation Time: 12 hours Result: Inhibited phosphatidylinositol 3-kinase (PI3K) and in-activates AKT-mTOR signaling.
In Vivo	KU-0060648 (intraperitoneal injection; 10 and 50 mg/kg; once daily; daily for 21 days) dramatically inhibits HepG2 xenograft growth in nude mice, the tumor weights (at week 5) of KU-0060648 group mice are dramatically lighter than that of vehicle control mice and exert a dose-dependent effect in vivo[1]. Animal Model: HepG2 xenograft nude mice model[1] Dosage: 10 and 50 mg/kg Administration: Intraperitoneal injection; 10 and 50 mg/kg; once daily; daily for 21 days Result: Suppressed HepG2 xenograft growth in nude mice.
References	[1]. Munck JM, et al. Chemosensitization of cancer cells by KU-0060648, a dual inhibitor of DNA-PK and PI-3K. Mol Cancer Ther. 2012 Aug;11(8):1789-98. [2]. Chen MB, et al. KU-0060648 inhibits hepatocellular carcinoma cells through DNA-PKcs-dependent and DNA-PKcs-independent mechanisms. Oncotarget. 2016 Mar 29;7(13):17047-59.

Density	1.3±0.1 g/cm3
Boiling Point	819.9±65.0 °C at 760 mmHg
Molecular Formula	C₃₃H₃₄N₄O₄S
Molecular Weight	582.713
Flash Point	449.7±34.3 °C
Exact Mass	582.230103
PSA	106.50000
LogP	5.56
Vapour Pressure	0.0±3.0 mmHg at 25°C
Index of Refraction	1.694
Storage condition	-20℃

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