PLX4720 | Mutant B-Raf inhibitor

PLX4720 (918505-84-7) is a potent and selective inhibitor of B-Raf, V600E mutant, IC₅₀=13 nM (Wild type IC₅₀=160 nM).¹ It induces cell cycle arrest and apoptosis in B-Raf^V600E-positive cells and suppresses growth of B-Raf^V600E-positive xenografts.¹ It induces tumor regression and reverses cachexia in a mouse model of human thyroid cancer harboring the B-Raf^V600E mutation.² Early stage autophagy inhibitors and ER stress inhibition with 4-phenylbutyric acid increases the sensitivity of resistant cells to PLX4720.³ PLX4720 induces cytoprotective autophagy in thyroid cancer cells via AMPK-ULK1 pathway.⁴

References/Citations:

1. Tsai et al. (2008), Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity; Proc. Natl. Acad. Sci. USA, 105 3041
2. Nehs et al. (2012), Late intervention with anti-BRAF(V600E) therapy induces tumor regression in an orthotopic mouse model of human anaplastic thyroid cancer; Endocrinology, 153 985
3. Yeom et al. (2021), Increase in the sensitivity to PLX4720 through inhibition of transcription factor EB-dependent autophagy in BRAF inhibitor-resistant cells; Toxicol. Res., 38 35
4. Jimenez-Morah et al. (2021), ^V600EBRAF Inhibition Induces Cytoprotective Autophagy through AMPK in Thyroid Cancer Cells; Int. J. Mol. Sci. 22 6033