|S1038||PI-103||<1 mg/mL||24 mg/mL||<1 mg/mL|
|S2638||NU7441 (KU-57788)||<1 mg/mL||4 mg/mL||<1 mg/mL|
|S1205||PIK-75||<1 mg/mL||4 mg/mL||<1 mg/mL|
|S2893||NU7026||<1 mg/mL||1 mg/mL||<1 mg/mL|
|S2622||PP121||<1 mg/mL||64 mg/mL||2 mg/mL|
|S8589||SF2523||<1 mg/mL||29 mg/mL||7 mg/mL|
|S8427||LTURM34||<1 mg/mL||82 mg/mL||4 mg/mL|
|S8379||YU238259||<1 mg/mL||91 mg/mL||<1 mg/mL|
|S8045||KU-0060648||<1 mg/mL||0.4 mg/mL||<1 mg/mL|
|S7891||CC-115||<1 mg/mL||67 mg/mL||<1 mg/mL|
|S8322||LY3023414||<1 mg/mL||47 mg/mL||61 mg/mL|
PI-103 is a multi-targeted PI3K inhibitor for p110α/β/δ/γ with IC50 of 2 nM/3 nM/3 nM/15 nM in cell-free assays, less potent to mTOR/DNA-PK with IC50 of 30 nM/23 nM.
(D) IGROV parental, shControl (two independent clones) and ShPKCiota (two independent clones) were treated with 5 μM GDC-0941 and 1.5 μM PI-103 for 24 hours and subjected to western blot analysis with the indicated antibodies. Each experiment was performed in triplicate.
NU7441 (KU-57788) is a highly potent and selective DNA-PK inhibitor with IC50 of 14 nM and also inhibits PI3K with IC50 of 5 μM in cell-free assays.
(C) Microirradiation live-cell microscopy of U2OS cells stably expressing mEGFP-MacroD2 full-length construct and treated with KU55933 10 μM, VE-821 1 μM, NU7441 1 μM or DMSO. Scale bar, 10 μm.
PIK-75 HCl is a p110α inhibitor with IC50 of 5.8 nM (200-fold more potently than p110β), isoform-specific mutants at Ser773, and also potently inhibits DNA-PK with IC50 of 2 nM in cell-free assays.
A549 cells were treated with DMSO or PIK-75 (200 nM) for 1 h and subsequently stimulated with izTRAIL for 24 h. Long-term survival was visualized after 7 days by crystal violet staining. One of two independent experiments is shown.
NU7026 is a potent DNA-PK inhibitor with IC50 of 0.23 μM in cell-free assays, 60-fold selective for DNA-PK than PI3K and inactive against both ATM and ATR.
M059K cells were transfected with Scrambled, ERCC1, EGFR, or EGFR–ERCC1 siRNA. Following 48 hours of siRNA transfection, Scrambled siRNA and ERCC1 siRNA-transfected cells were treated with 1 µmol/L gefitinib or 125 nMol/L NU7026, or both, while EGFR siRNA and EGFR–ERCC1 siRNA-transfected cells were treated with 125 nMol/L of NU7026 1 hour prior 4 Gy IR treatment. Survival of these cells was then assessed 72 hours following IR treatment via MTT assay.
PP-121 is a multi-targeted inhibitor of PDGFR, Hck, mTOR, VEGFR2, Src and Abl with IC50 of 2 nM, 8 nM, 10 nM, 12 nM, 14 nM and 18 nM, also inhibits DNA-PK with IC50 of 60 nM.
PP121 induces apoptosis in ATC cells. CAL62 cells were treated with PP121 at the indicated concentrations for 48 h, followed by PI staining. The nuclei were stained with Hoechst and analyzed using a fluorescent microscope. The representative images are shown.
SF2523 is a highly selective and potent inhibitor of PI3K with IC50 values of 34 nM, 158 nM, 9 nM, 241 nM and 280 nM for PI3Kα, PI3Kγ, DNA-PK, BRD4 and mTOR, respectively.
LTURM34 is a specific DNA-PK inhibitor, 170-fold more selective for DNA-PK activity compared to PI3K activity, with IC50 value of 0.034 μM.
YU238259 is a novel inhibitor of homology-dependent DNA repair(HDR), but does not inhibit non-homologous end-joining (NHEJ), in cell-based GFP reporter assays.
KU-0060648 is a dual inhibitor of DNA-PK and PI3Kα, PI3Kβ, PI3Kδ with IC50 of 8.6 nM and 4 nM, 0.5 nM, 0.1 nM respectively, less inhibition of PI3Kγ with IC50 of 0.59 μM.
CC-115 is a dual inhibitor of DNA-dependent protein kinase (DNA-PK) and mammalian target of rapamycin (mTOR), with potential antineoplastic activity.
LY3023414 is an oral ATP competitive inhibitor of the class I PI3K isoforms, mTOR and DNA-PK.