Multi-kinase (Regorafenib target profile) (MKI)

Regorafenib targets a diverse set of protein kinases that are instrumental in tumor growth, angiogenesis, and the maintenance of the tumor microenvironment. Its primary inhibitory activity is directed against vascular endothelial growth factor receptors (VEGFR1, VEGFR2, and VEGFR3) and the TIE2 receptor, which are essential for the formation of new blood vessels within tumors [Wilhelm et al., 2011]. Additionally, it inhibits platelet-derived growth factor receptor (PDGFR-beta) and fibroblast growth factor receptor (FGFR1), which modulate the surrounding stroma and support tumor progression [FDA Label, 2020]. The drug also acts on oncogenic kinases such as KIT, RET, and BRAF (including the V600E mutation), directly suppressing tumor cell proliferation and survival pathways [PubChem CID 11167105]. By targeting the colony-stimulating factor 1 receptor (CSF1R), regorafenib may also influence tumor-associated macrophages and the immune response within the tumor [Grothey et al., 2013]. This broad-spectrum inhibition is designed to overcome the redundancy and resistance often seen with more selective kinase inhibitors. Clinically, this profile makes regorafenib effective in treating advanced malignancies such as metastatic colorectal cancer, gastrointestinal stromal tumors, and hepatocellular carcinoma [Bruix et al., 2017].

Other names

Vascular endothelial growth factor receptor (VEGFR)Platelet-derived growth factor receptor (PDGFR)Fibroblast growth factor receptor (FGFR)KIT proto-oncogene receptor tyrosine kinase (c-KIT)RET proto-oncogeneRAF-1 proto-oncogene serine/threonine-protein kinase (CRAF)BRAF serine/threonine-protein kinaseTEK receptor tyrosine kinase (TIE2)Colony stimulating factor 1 receptor (CSF1R)

Regorafenib acts as a small-molecule multi-kinase inhibitor that binds to the adenosine triphosphate (ATP) binding site of various kinases, thereby inhibiting their phosphorylation and downstream signaling pathways [Wilhelm et al., 2011].