KU-0060648

Research use only, not for human use.

KU-006064 is a potent, dual inhibitor of DNA-PK and PI3K.

KU-006064 is a potent, dual inhibitor of DNA-PK (IC50=8.6 nM) and PI3K (IC50=4/0.5/0.1 nM for PI3Kα/β/δ); shows selectively over other PI-3K-like kinases, such as ATM, ATR and mTOR; inhibits cellular DNA-PK autophosphorylation with IC50 of 19 nM (MCF7 cells) and 170 nM (SW620 cells); reduces the frequency of NHEJ while increasing the rate of HDR following Cas9-mediated DNA cleavage.

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).KU-0060648 (30-500 nM; 72 hours) dose-dependently inhibits HepG2 cell proliferation, IC50=134.32nM.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.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. Cell Proliferation Assay 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 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.

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. Animal Model:HepG2 xenograft nude mice modelDosage: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.

KU0060648

Cell Cycle/DNA Damage

DNA-PK

DNA-PK|PI3Kα|PI3Kβ|PI3Kγ|PI3Kδ

Cancer

——

881375-00-4

582.719

C33H34N4O4S

>98% (HPLC)

2eq.HCl: 58.3 mg/mL (100 mM) （ < 1 mg/ml refers to the product slightly soluble or insoluble )

O=C1C=C(N2CCOCC2)OC3=C(C4=C5C(C6=CC=CC=C6S5)=C(NC(CN7CCN(CC7)CC)=O)C=C4)C=CC=C13

4-ethyl-N-[4-[2-(4-morpholinyl)-4-oxo-4H-1-benzopyran-8-yl]-1-dibenzothienyl]-1-piperazineacetamide

(-20℃)

With Ice Pack

≥ 2 years