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• A selective, potent paradox-breaker BRAFi that targets mutated BRAF monomers and homodimers and BRAF-CRAF heterodimers without inducing RAF dimer formation • Demonstrated robust anti-tumor activity as a single agent against BRAF-altered tumors including CNS tumors, with durable long-term tolerability, no dose limiting toxicities, infrequent symptomatic G3 AEs, infrequent fever, and no skin toxicities observed with approved BRAFi in clinical settings • This work evaluates the combination of plixorafenib and MEKi in nonclinical models and explored the feasibility of the combination for clinical use Methods • High-throughput cell-based functional assay quantifies MAPK signaling pathway activation using fluorescent imaging coupled with image analysis of cells expressing the mutated protein together with a荧光标记为ERK2为信号途径报道器（Zimmerman，L。et al。SCI。 Rep。63，4192（2020））•使用标准的Western印迹和细胞活力测定法验证了高通量测定结果SCI。Rep。63，4192（2020））•使用标准的Western印迹和细胞活力测定法验证了高通量测定结果Rep。63，4192（2020））•使用标准的Western印迹和细胞活力测定法验证了高通量测定结果
悖论的BRAF抑制剂PLIXORAFENIB（PLX8394
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