Drug intelligence / Profile preview

pazopanib + gemcitabine + cisplatin

Development stage
Phase 1
Lead developer
Novartis
Modality
Small Molecules
Administration
Oral, Intravenous
01

Overview

This triple combination is composed of **pazopanib**, a multi-targeted small molecule tyrosine kinase inhibitor primarily acting against VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-α, PDGFR-β, FGFR-1, FGFR-3, and c-Kit; **gemcitabine**, a cytotoxic nucleoside analogue that incorporates into DNA and inhibits DNA synthesis; and **cisplatin**, a platinum-based chemotherapy agent that forms DNA crosslinks and thereby inhibits DNA replication. This combination has been investigated in early-phase clinical trials for advanced solid tumors and refractory soft-tissue sarcoma but is not an approved regimen. Pazopanib exerts antiangiogenic and antiproliferative effects via kinase inhibition. Gemcitabine impairs DNA synthesis, resulting in inhibition of cancer cell proliferation. Cisplatin induces apoptosis through DNA adduct formation. Combined, these agents aim to exploit different antitumor pathways but may be limited by increased toxicity, particularly myelosuppression and organ-specific toxicities.

02

Targets

CSF1R (Macrophage colony-stimulating factor receptor)DNAFGFR1 (Fibroblast growth factor receptor 1)FGFR3 (Fibroblast 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)RNR (Ribonucleotide reductase)VEGFR-1 (Vascular endothelial growth factor receptor 1)VEGFR2 (Vascular endothelial growth factor receptor 2)VEGFR4 (Vascular endothelial growth factor Receptor-3)

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