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vandetanib + dasatinib
- Development stage
- Phase 1
- Lead developer
- AstraZeneca
- 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
Vandetanib + dasatinib is a combination of two small molecule tyrosine kinase inhibitors investigated primarily for the treatment of diffuse intrinsic pontine glioma (DIPG) in pediatric patients. Vandetanib acts as a potent inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), epidermal growth factor receptor (EGFR), and RET tyrosine kinases, thereby inhibiting angiogenesis and tumor cell proliferation. Dasatinib is a multi-targeted kinase inhibitor with strong activity against platelet-derived growth factor receptors (PDGFRs) and Src family kinases. The rationale for combining these agents lies in their complementary inhibition of critical signaling pathways involved in glioma pathogenesis—VEGF/VEGFR-mediated angiogenesis and PDGF/PDGFR-driven tumor cell survival and proliferation. This combination has been evaluated in phase I clinical trials during and after radiotherapy for children with newly diagnosed DIPG[1][2][3][4].
- Other names
- vandetanib + dasatinib
02
Targets
ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase)EGFR (Epidermal growth factor receptor)RET (Rearranged during transfection receptor tyrosine kinase)SFK (SRC family kinases)VEGFR2 (Vascular endothelial growth factor receptor 2)VEGFR4 (Vascular endothelial growth factor Receptor-3)KIT (c-KIT proto-oncogene receptor tyrosine kinase)PDGFRA (Platelet-derived growth factor receptor alpha)PDGFRB (Platelet-derived growth factor receptor beta)
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