Among the various cytoplasmic kinases, RAF (Rapidly Accelerated Fibrosarcoma) is one of the kinases that participate in the linear Ras-RAF-MEK-ERK mitogen-activated protein kinase (MAPK) pathway initiated by a receptor protein kinase, which is activated by a growth factor[1]. Belvarafenib, currently in Phase 1 clinical trials, is a selective and orally bioavailable pan-RAF kinase inhibitor. When biochemically assayed for hundreds of kinases, Belvarafenib showed selectivity toward RAF family kinases, including strong inhibition activities for BRAF WT, BRAF mutants and CRAF. Belvarafenib strongly inhibits the growth of cancer cell lines with BRAF, NRAS or KRAS mutations and also shows excellent anticancer efficacy in animal models using the corresponding cancer cells. The phosphorylation of ERK, AKT and S6K are inhibited after the treatment of Belvarafenib in the above cancer cells of BRAF, NRAS or KRAS mutations[2]. Belvarafenib was well tolerated and exhibited anti-tumor activity in patients with advanced solid tumors harboring RAS or RAF mutations[3]
Belvarafenib 细胞实验
Cell Line
Concentration
Treated Time
Description
References
SK-MEL-30
1 to 0.002 µM
120 hours
Evaluate the effect of Belvarafenib and Cobimetinib on NRAS mutant cells, showing synergistic effects in the NRAS mutant context.
Cancers (Basel). 2024 Aug 22;16(16):2914.
SK-MEL-2
1 to 0.002 µM
120 hours
Evaluate the effect of Belvarafenib and Cobimetinib on NRAS mutant cells, showing synergistic effects in the NRAS mutant context.
Cancers (Basel). 2024 Aug 22;16(16):2914.
MEL-JUSO
1 to 0.002 µM
120 hours
Evaluate the effect of Belvarafenib and Cobimetinib on NRAS mutant cells, showing synergistic effects in the NRAS mutant context.
Cancers (Basel). 2024 Aug 22;16(16):2914.
IPC-298
1 to 0.002 µM
120 hours
Evaluate the effect of Belvarafenib and Cobimetinib on NRAS Q61L mutant cells, showing synergistic effects in the NRAS mutant context.
Cancers (Basel). 2024 Aug 22;16(16):2914.
A375
1 to 0.002 µM
120 hours
Evaluate the effect of Belvarafenib and Cobimetinib on BRAF V600E mutant cells, showing additive effects in the BRAF mutant context.
Cancers (Basel). 2024 Aug 22;16(16):2914.
IPC-298 cells
10 µM
90 days
Investigated the transcriptomic response of melanoma cells to Belvarafenib, discovering a rare resistant cell population (0.12%)
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