BI-847325

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种新型 ATP 竞争性 MEK/Aurora 激酶抑制剂；抑制人类 Aurora A (IC50=25 nM) 和 Aurora C (IC50=16 nM)。

A novel ATP-competitive MEK/Aurora kinase inhibitor; inhibts human Aurora A (IC50=25 nM) and Aurora C(IC50=16 nM); also inhibits MEK1 (IC50=25 nM) and MEK2 (IC50=6 nM); reduces expression of p-ERK and p-Histone 3 in multiple models of vemurafenib resistance; decreases the expression of MEK and Mcl-1 and increases the expression of BIM; orally bioavailable.Solid Tumors Phase 1 Clinical(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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BI847325 | BI 847325

MAPK/ERK Signaling

MEK

AuroraA(Human)|AuroraB(Xenopuslaevis)|AuroraC(Human)|MEK1|MEK2

Cancer

Solid Tumors

1207293-36-4

464.5582

C29H28N4O2

>98% (HPLC)

DMSO: ≥36 mg/mL

O=C(NCC)C#CC1=CC(NC/2=O)=C(C=C1)C2=C(NC3=CC=C(CN(C)C)C=C3)/C4=CC=CC=C4

2-Propynamide, 3-[3-[[[4-[(dimethylamino)methyl]phenyl]amino]phenylmethylene]-2,3-dihydro-2-oxo-1H-indol-6-yl]-N-ethyl-

(-20℃)

With Ice Pack

≥ 2 years