Proto-oncogene tyrosine-protein kinase KIT, Proto-oncogene tyrosine-protein kinase Src, Platelet-derived growth factor receptor beta, and Proto-oncogene tyrosine-protein kinase receptor Ret (KIT/SRC/PDGFRB/RET)

This target profile represents a specific cluster of tyrosine kinases—Proto-oncogene tyrosine-protein kinase KIT (c-Kit), Proto-oncogene tyrosine-protein kinase Src (c-SRC), Platelet-derived growth factor receptor beta (PDGFR-β), and Proto-oncogene tyrosine-protein kinase receptor Ret (Ret)—that are key therapeutic targets for several multi-kinase inhibitors (MKIs) in oncology [1, 2]. These proteins are integral to signaling pathways that drive tumor growth, survival, and the formation of new blood vessels [6]. KIT and RET are receptor tyrosine kinases (RTKs) that, when mutated or rearranged, act as primary oncogenic drivers in gastrointestinal stromal tumors (GIST) and various thyroid cancers [2, 7]. PDGFR-β is an RTK that regulates the recruitment of supporting cells to the tumor vasculature, while c-SRC is a non-receptor tyrosine kinase that facilitates cross-talk between various signaling pathways to promote tumor invasion and metastasis [1, 4]. Drugs such as apatinib (rivoceranib) and ponatinib are characterized by their ability to simultaneously inhibit these four kinases, providing a multi-pronged approach to treating advanced malignancies like gastric cancer and chronic myeloid leukemia [3, 7]. However, the simultaneous inhibition of these diverse signaling nodes is associated with significant safety concerns, including hypertension, dermatological toxicities, and potential cardiotoxicity [4, 9].

Other names

c-Kitc-SRCPDGFR-betaRetKITSRCPDGFRBRETCD117SCFRp185-RetCD140bTyrosine-protein kinase KITProto-oncogene c-KitProto-oncogene tyrosine-protein kinase receptor Ret

ATP-competitive inhibition of the tyrosine kinase domain, preventing autophosphorylation and downstream signaling cascades.