BI-882370 是一种高效选择性的 RAF 激酶抑制剂，其结合位于 BRAF 激酶的 DFG-out 无活性构象处 (ATP 结合位点)。 BI-882370 抑制 BRAF^V600E-mutant, WT BRAF 和 CRAF 激酶的 IC₅₀ 值分别为 0.4，0.8 和 0.6 nM。BI-882370 也可以抑制 SRC 家族激酶。

BI-882370 is a potent and selective RAF kinase inhibitor that binds to the ATP binding site of the kinase positioned in the DFG-out (inactive) conformation of the BRAF kinase. BI-882370 (BI 882370) inhibits the oncogenic BRAF-mutant, the WT BRAF and CRAF kinases with IC 50 s of 0.4, 0.8, and 0.6 nM, respectively. BI-882370 also inhibits SRC family kinases.

Solid

Braf 0.6 nM (IC50) c-Raf 0.8 nM (IC50

BI-882370 (0.9-6000 nM; 3 days) inhibits the BRAF-mutant human melanoma and colorectal cancer cells proliferation with a EC50 range of 1-10 nM.
BI 882370 (0.1-100 nM, 0.1-3000 nM; 2 hours) results in a reduction of p-MEK1/2, p-ERK1/2 and cyclin D1/D2 expression in BRAF-mutant A375 cells; induces phosphorylation of MEK1/2 and enhanced phosphorylation of ERK1/2 in WT BRO cells (3-300 nM).
BI 882370 (0.1-100 nM, 0.1-3000 nM; 24 hours) suppresses cyclin D1/D2 expression, induces Kip1/p27 expression at concentrations of 1 nM or higher in BRAF-mutant A375 cells, expression of cyclins D1/D2 or Kip1/p27 is not affected in WT BRO cells.
has not independently confirmed the accuracy of these methods. They are for reference only.

BI-882370 (deliver orally; 25 mg/kg, 50 mg/kg; twice daily; 2 weeks) is efficacious in multiple mouse models of BRAF-mutant melanomas and colorectal carcinomas, shows superior efficacy compared with Vemurafenib, Dabrafenib, or Trametinib.
BI-882370 (deliver orally; 25 mg/kg; twice daily; 40 days) developes resistance within 3 weeks, but resistance is not observed during 5 weeks of second-line therapy in combination with trametinib.
BI-882370 (deliver orally; 60 mg/kg; once daily; 2 weeks) indicates lack of toxicity in terms of clinical chemistry, hematology, pathology, and toxicogenomics in rats. has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[1]. Waizenegger IC, et al. A Novel RAF Kinase Inhibitor with DFG-Out-Binding Mode: High Efficacy in BRAF-Mutant Tumor Xenograft Models in the Absence of Normal Tissue Hyperproliferation. Mol Cancer Ther. 2016 Mar;15(3):354-65.

In Vitro: DMSO : 5 mg/mL (8.78 mM; ultrasonic and warming and heat to 60°C)H₂O : < 0.1 mg/mL (insoluble)配制储备液