Pazopanib Hydrochloride

Pazopanib Hydrochloride is an oral multi-targeted kinase inhibitor indicated for the treatment of advanced renal cell carcinoma and soft tissue sarcoma. As a potent antiangiogenic agent, Pazopanib Hydrochloride selectively inhibits vascular endothelial growth factor receptors (VEGFR), platelet-derived growth factor receptors (PDGFR), and c-Kit, leading to inhibition of angiogenesis and tumour growth. Pazopanib Hydrochloride inhibits ligand-induced autophosphorylation of VEGFR-2, Kit, and PDGFR-β receptors in vitro, and in vivo it reduces tumour growth in xenograft models. Pazopanib Hydrochloride and its related impurities serve as critical reference standards for analytical method development, method validation (AMV), and quality control (QC) in ANDA filings.

Product Parameters

Application

Pazopanib Hydrochloride is an oral angiogenesis inhibitor targeting VEGFR and PDGFR.

Mechanism of action

Pazopanib Hydrochloride is a multi-target tyrosine kinase inhibitor that inhibits angiogenesis, used for the treatment of advanced renal cell carcinoma (renal cell carcinoma, RCC). Tyrosine kinase is the most common growth factor receptor. Most RCC patients have VHL gene mutations and abnormal growth of tumor tissues, leading to hypoxia-inducible factor (HIF)-related transcriptional activation, which causes overexpression of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and transforming growth factor 2α (TGF2α). These factors activate the Raf/MEK/ERK and PI3K/Akt/mTOR pathways through autophosphorylation of receptor tyrosine kinases, resulting in uncontrolled cell division, proliferation and transformation, stimulating neovascularization, and promoting tumor growth and metastasis. Pazopanib can selectively inhibit VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-α, PDGFR-β and C-Kit. By blocking tyrosine kinases, it can disrupt the signal transduction of tumor cells, thereby inhibiting tumor cell proliferation and neovascularization, and achieving the anti-tumor effect.

Notes

Pazopanib Hydrochloride oral tablets are available in two specifications: 200mg and 400mg. The recommended dose for the treatment of advanced renal cell carcinoma is 800mg once daily. For patients with moderate hepatic impairment, the dosage can be adjusted to 200mg per day; this drug has not been evaluated in patients with severe hepatic impairment, so it is not recommended for such patients from Chemicalbook. Concomitant use of CYP3A4 (cytochrome P450 3A4 enzyme) inhibitors and inducers (such as ketoconazole, ritonavir, rifampicin, etc.) should be avoided as much as possible when taking this drug. If patients do need to take the above drugs concomitantly, the dose of Pazopanib Hydrochloride should be adjusted accordingly. This product is harmful to the fetus and is contraindicated during pregnancy.

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