BI-847325 Property

storage temp. 

Store at -20°C

solubility 

≥24.1 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O

form 

crystalline solid

color 

Light yellow to yellow

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

BI-847325 Chemical Properties,Usage,Production

Description

BI-847325 is a selective dual MEK/Aurora kinase inhibitor with IC₅₀ values of 3, 25, 15, 25, and 4 nM for X. laevis Aurora B, human Aurora A and Aurora C, and human MEK1 and MEK2, respectively. It can inhibit the growth and survival of both treatment-naive and drug-resistant melanoma cell lines, decreasing the expression of MEK and Mcl-1 while increasing the expression of pro-apoptotic protein Bim. At 70 mg/kg, BI-847325 induces apoptosis in treatment-naive and drug-resistant xenografted melanoma in vivo.

Uses

BI-847325 is a novel ATP-competitive MEK and Aurora kinase inhibitor. It can inhibit the growth of BRAF resistant melanoma cells through suppression of Mcl-1 and MEK expression in human melanoma cell lines and mouse xenograft model. The efficacy of BI-847325 was studied in patients with refractory solid tumors.

References

[1]. sini p, gürtler u, zahn sk, et al. pharmacological characterization of bi 847325, a dual inhibitor of mek and aurora kinases. cancer research, 2012, 72(8 supplement): 1919-1919.
[2]. hideshima t, chauhan d, richardson p, et al. nf-κb as a therapeutic target in multiple myeloma. journal of biological chemistry, 2002, 277(19): 16639-16647.
[3]. rommel c, clarke ba, zimmermann s, et al. differentiation stage-specific inhibition of the raf-mek-erk pathway by akt. science, 1999, 286(5445): 1738-1741..