Various non-RAF kinases

The term "Various non-RAF kinases" refers to a heterogeneous group of protein kinases, primarily receptor tyrosine kinases (RTKs), that are inhibited by multi-kinase inhibitors in addition to their activity against the RAF family (ARAF, BRAF, and CRAF) [1]. This collective group typically includes Vascular Endothelial Growth Factor Receptors (VEGFR-1, -2, -3), Platelet-Derived Growth Factor Receptors (PDGFR-alpha and -beta), KIT, FLT3, and RET [2]. These kinases are essential mediators of signal transduction pathways involved in angiogenesis, lymphangiogenesis, and the maintenance of the tumor stroma [3]. In clinical oncology, targeting these non-RAF kinases is a strategy used to treat solid tumors such as hepatocellular carcinoma and renal cell carcinoma by simultaneously disrupting tumor cell proliferation and blood supply [4]. However, the broad-spectrum activity against these various kinases is also responsible for significant systemic toxicities, including hypertension, hand-foot skin reaction, and gastrointestinal distress [5]. Sources: [1] Wilhelm SM, et al. Nature Reviews Drug Discovery (2004); [2] PubChem Compound Summary for CID 111671 (Sorafenib); [3] Wilhelm SM, et al. International Journal of Cancer (2011); [4] FDA Label: Nexavar (sorafenib) tablets; [5] StatPearls: Kinase Inhibitors (2023).

Other names

Non-RAF kinase targetsOff-target kinasesMulti-kinase inhibitor targetsCollateral kinases

Competitive inhibition of the adenosine triphosphate (ATP) binding site across multiple distinct protein kinases, leading to the suppression of downstream signaling pathways such as MAPK/ERK and PI3K/AKT.