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VE-821

CAS No. : 1232410-49-9

產品活性：VE-821 is a potent ATP-competitive inhibitor of ATR with K_i/IC₅₀ of 13 nM/26 nM.

研究領域：Cell Cycle/DNA Damage  |  PI3K/Akt/mTOR

作用靶點：ATM/ATR

In Vitro: VE-821 shows excellent selectivity for ATR with minimal cross-reactivity against the related PIKKs ATM, DNA-PK, mTOR and PI3Kγ (K_is of 16 μM, 2.2 μM, >1 μM and 3.9 μM, respectively) and against a large panel of unrelated protein kinases. VE-821 (compound 27) also inhibits ATM and DNA-PK wirh IC₅₀ of >8 μM, and 4.4 μM, respectively. VE-821 significantly enhances the sensitivity of PSN-1, MiaPaCa-2 and primary PancM pancreatic cancer cells to radiation and Gemcitabine under both normoxic and hypoxic conditions. ATR inhibition by VE-821 leads to inhibition of radiation-induced G₂/M arrest in cancer cells. In both PSN-1 and MiaPaCa-2 cells, 1 µM VE-821 inhibits phosphorylation of Chk1 (Ser 345) after treatment with Gemcitabine (100 nM), radiation (6 Gy) or both, at 2 h post-irradiation.

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