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BI-847325

CAS No. : 1207293-36-4

产品活性：BI-847325 is an ATP competitive dual inhibitor of MEK and aurora kinases (AK) with IC₅₀ values of 4 and 15 nM for human MEK2 and AK-C, respectively.

研究领域：MAPK/ERK Pathway  |  Epigenetics  |  Cell Cycle/DNA Damage  |  Apoptosis

作用靶点：MEK  |  Aurora Kinase  |  Apoptosis

In Vitro: BI 847325 inhibits the activity of X. laevis AK-B with an IC₅₀ of 3 nM; the IC₅₀ values for human AK-A and AK-C are 25 and 15 nM, respectively. BI 847325 also inhibits human MEK1 and MEK2 with respective IC₅₀ values of 25 and 4 nM. BI 847325 at 1,000 nM inhibits 6 enzymes by more than 50% (LCK, MAP3K8, FGFR1, AMPK, CAMK1D and TBK1) and the IC₅₀ values are below 100 nM only for LCK (5 nM) and MAP3K8 (93 nM). Proliferation is inhibited in A375 and Calu-6 cell lines with GI₅₀ values of 7.5 nM and 60 nM, respectively.

In Vivo: Daily oral administration of BI 847325 at 10 mg/kg shows efficacy in both BRAF- and KRAS-mutant xenograft models. BI 847325 administered once weekly at 70 mg/kg inhibits both MEK and AK in KRAS-mutant tumors.

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