Drug intelligence / Profile preview

crizotinib + sunitinib

Development stage
Unknown
Lead developer
Pfizer
Modality
Orthosteric Ligands → Classical Binding Small Molecules → Small Molecules, Allosteric Modulators → Classical Binding Small Molecules → Small Molecules, Irreversible Covalent Inhibitors → Covalent Small Molecules → Small Molecules
Administration
Oral
01

Overview

Crizotinib + sunitinib is a combination of two small-molecule tyrosine kinase inhibitors used primarily in oncology research. Crizotinib targets anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 receptor tyrosine kinase (ROS1), and MET proto-oncogene receptor tyrosine kinase (MET), inhibiting their activity to block tumor cell proliferation and survival. It is approved for ALK- or ROS1-positive non-small cell lung cancer (NSCLC), as well as ALK-positive anaplastic large cell lymphoma and inflammatory myofibroblastic tumor[4]. Sunitinib inhibits multiple receptor tyrosine kinases including platelet-derived growth factor receptor alpha, platelet-derived growth factor receptor beta, vascular endothelial growth factor receptor (VEGFR), KIT proto-oncogene receptor tyrosine kinase (KIT) (CD117), RET proto-oncogene receptor tyrosine kinase (RET), colony stimulating factor 1 receptor (CSF-1R), and FLT3 proto-oncogene (FLT3). This broad inhibition disrupts tumor angiogenesis and proliferation; it is approved for renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumors[5][6]. Both drugs are associated with hepatotoxicity mediated by mitochondrial oxidative stress when used individually or together[1][3].

02

Targets

AXL (AXL receptor tyrosine kinase)CSF1R (Macrophage colony-stimulating factor receptor)ALK (Anaplastic lymphoma kinase receptor tyrosine kinase)VEGFR4 (Vascular endothelial growth factor Receptor-3)MST1R (Recepteur d'origine nantais)MET (Mesenchymal-epithelial transition factor receptor)PDGFRA (Platelet-derived growth factor receptor alpha)FLT3 (Fms related receptor tyrosine kinase 3)RET (Rearranged during transfection receptor tyrosine kinase)MERTK (MER proto-oncogene, tyrosine kinase)EPH (EPH receptor family)VEGFR-1 (Vascular endothelial growth factor receptor 1)ROS1 (Proto-oncogene tyrosine-protein kinase ROS)VEGFR2 (Vascular endothelial growth factor receptor 2)PDGFRB (Platelet-derived growth factor receptor beta)KIT (c-KIT proto-oncogene receptor tyrosine kinase)

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