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A. B. Biochemical Assays ( µ M ) ATR 0.00023 ATM 1.4 DNAPKcs 7.3 mTOR 5.2 PIK3CA >9.1 PI3 b , g , d > 9.1. Cellular Assays (µM ) ATR-pCHK1 S345 0.13 mTOR-pS6K T398 2.1. Supplementary Figure 1. A. mTORi =AZD8055 ( -H2AX E C 50 (+HU) >10 M).
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A. B. Biochemical Assays (µM) ATR 0.00023 ATM 1.4 DNAPKcs 7.3 mTOR 5.2 PIK3CA >9.1 PI3b, g, d >9.1 Cellular Assays (µM) ATR-pCHK1 S3450.13 mTOR-pS6K T398 2.1 Supplementary Figure 1
A. mTORi=AZD8055 (-H2AX EC50 (+HU) >10M) DNA-PKcsi=NU7441 (-H2AX EC50 (+HU) >10M) B. ATRi/mTORi (-H2AXEC50 (+HU)=7M) ATMi=KU55933 (-H2AX EC50 (+HU)>10M) C. D. Supplementary Figure 2
A. untreated (0.4%) 1 µM ATRi (2.3%) B. 1 µM gemcitabine + 1 µM ATRi (58.7%) 1 µM gemcitabine (2.2%) H2AX-FITC PI C. 1 µM cytarabine + 1 µM ATRi (42.0%) 1 µM cytarabine (0.6%) 1 µM clofarabine + 1 µM ATRi (47%) D. 1 µM clofarabine (6.4%) E. 5 µM cladribine + 1 µM ATRi (40.4%) 5 µM cladribine (7.3%) Supplementary Figure 3
A. ATRi 2 h ATRi 24 h B. DMSO 0.5 µM 1.0 µM DMSO 0.5 µM 1.0 µM Supplementary Figure 4
B. A. C. D. Supplementary Figure 5