Golvatinib

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Golvatinib is an investigational tyrosine kinase inhibitor that targets multiple receptor tyrosine kinases, including c-Met and VEGFR-2. It is being studied for its potential use in the treatment of various types of cancer, particularly those that exhibit overexpression or dysregulation of these receptors.

Mechanism of Action

Golvatinib functions by inhibiting the activity of receptor tyrosine kinases, which are enzymes that play a crucial role in the signaling pathways that regulate cell division, survival, and migration. By blocking these pathways, golvatinib can potentially reduce tumor growth and metastasis.

The primary targets of golvatinib are:

• c-Met: A receptor that, when activated, can lead to increased tumor cell proliferation, survival, and metastasis. Overexpression of c-Met is associated with poor prognosis in several cancers.
• VEGFR-2: A receptor involved in angiogenesis, the process by which new blood vessels form from pre-existing vessels. Inhibition of VEGFR-2 can reduce the blood supply to tumors, thereby inhibiting their growth.

Clinical Development

Golvatinib is currently undergoing clinical trials to evaluate its efficacy and safety in treating various cancers, including hepatocellular carcinoma, gastric cancer, and non-small cell lung cancer. Early-phase trials have shown promising results, with some patients experiencing partial responses or stable disease.

Pharmacokinetics

Golvatinib is administered orally and has a bioavailability that allows for effective systemic exposure. The drug is metabolized primarily in the liver, and its elimination involves both renal and fecal pathways. The half-life of golvatinib supports once-daily dosing in clinical settings.

Adverse Effects

Common adverse effects observed in clinical trials include:

• Fatigue
• Nausea
• Diarrhea
• Hypertension
• Hand-foot syndrome

These side effects are generally manageable with supportive care and dose adjustments.

Research and Future Directions

Ongoing research is focused on identifying biomarkers that predict response to golvatinib, optimizing dosing regimens, and exploring combination therapies with other anticancer agents. The potential for golvatinib to overcome resistance to other tyrosine kinase inhibitors is also being investigated.

Also see

• Tyrosine kinase inhibitor
• c-Met
• VEGFR-2
• Hepatocellular carcinoma
• Gastric cancer
• Non-small cell lung cancer