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pazopanib + paclitaxel
- Development stage
- Phase 2
- Lead developer
- GSK
- Modality
- Classical Binding Small Molecules → Small Molecules, Covalent Small Molecules → Small Molecules, Nucleic Acid-Directed Small Molecules → Small Molecules
- Administration
- Oral, Intravenous
01
Overview
Pazopanib + paclitaxel is a combination regimen of two antineoplastic agents used in the treatment of various solid tumors, including advanced renal cell carcinoma and soft tissue sarcoma. Pazopanib is an oral small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor 1 (VEGFR1), vascular endothelial growth factor receptor 2 (VEGFR2), vascular endothelial growth factor receptor 3 (VEGFR3), platelet-derived growth factor receptor alpha (PDGFRA), platelet-derived growth factor receptor beta (PDGFRB), c-Kit, FGFR, IL-2 receptor, LcK and c-Fms. By inhibiting these kinases involved in angiogenesis and tumor proliferation pathways such as RAS/RAF/MEK/ERK and PI3K/AKT/mTOR, pazopanib blocks tumor blood vessel formation and growth[3][5][6]. Paclitaxel is a microtubule-stabilizing agent that binds to the β subunit of tubulin to prevent microtubule disassembly during mitosis. This disrupts cell division and induces apoptosis in cancer cells[8]. The combination has shown synergistic antitumor effects due to complementary mechanisms—pazopanib’s antiangiogenic activity enhances the cytotoxic effect of paclitaxel on rapidly dividing tumor cells[1][4]. Pazopanib can also increase plasma concentrations of paclitaxel by weakly inhibiting CYP3A4/CYP2C8-mediated metabolism[1][6].
- Brand names
- Abraxane
02
Targets
BRAF (B-Raf proto-oncogene, serine/threonine kinase)BCL-2 (BCL-2 family)CSF1R (Macrophage colony-stimulating factor receptor)FGFR1 (Fibroblast growth factor receptor 1)FGFR3 (Fibroblast growth factor receptor 3)PDGFRA (Platelet-derived growth factor receptor alpha)PDGFRB (Platelet-derived growth factor receptor beta)VEGFR-1 (Vascular endothelial growth factor receptor 1)VEGFR2 (Vascular endothelial growth factor receptor 2)VEGFR4 (Vascular endothelial growth factor Receptor-3)KIT (c-KIT proto-oncogene receptor tyrosine kinase)FGFR (FGFR family)TUBB (Tubulin (alpha and beta subunits))
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