Receptor tyrosine kinases and Rapidly Accelerated Fibrosarcoma kinases (RTK/Raf)

Donafenib is a multi-kinase inhibitor that targets Receptor Tyrosine Kinases (RTKs), including Vascular Endothelial Growth Factor Receptors (VEGFR) and Platelet-Derived Growth Factor Receptors (PDGFR), as well as the Raf/MEK/ERK signaling pathway, specifically C-Raf and B-Raf kinases (PMID: 34143719). These targets play pivotal roles in regulating cell proliferation, differentiation, and angiogenesis (PMID: 32504333). In many cancers, particularly hepatocellular carcinoma (HCC), these pathways are overactivated, driving tumor growth and the formation of new blood vessels (PMID: 34143719). By inhibiting these kinases, donafenib effectively blocks downstream signaling through the Mitogen-Activated Protein Kinase (MAPK) cascade, leading to reduced tumor cell survival and suppressed tumor vascularization (PMID: 32504333). As a deuterated derivative of sorafenib, donafenib offers improved pharmacokinetic stability and a favorable safety profile while maintaining high efficacy against these molecular targets (PMID: 34143719).

Other names

Vascular endothelial growth factor receptorPlatelet-derived growth factor receptorC-RafB-RafRaf kinaseVEGFRPDGFRMAPK pathway kinases

Donafenib acts as a multi-kinase inhibitor that targets various receptor tyrosine kinases (such as VEGFR and PDGFR) and serine/threonine kinases in the Raf/MEK/ERK pathway, thereby inhibiting both tumor cell proliferation and tumor angiogenesis.