Golvatinib

Golvatinib
Golvatinib
Chemical nomenclature
IUPAC name	N-(4-((3-(1H-indazol-4-yl)-1H-pyrazol-4-yl)oxy)-3-fluorophenyl)-N'-(4-fluorophenyl)urea
Identifiers
CAS Number	928037-13-2
PubChem	16054624
ChemSpider	17286448
UNII	3F0K3T4OSM
KEGG	D09950
ChEMBL	1234567
Chemical data
Chemical formula	C22H15N5O2F2
Molecular weight	419.38 g/mol

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

Receptor Tyrosine Kinase Inhibitors

Name	Target	Indications	Notes
Imatinib	BCR-ABL	Chronic myeloid leukemia, Gastrointestinal stromal tumor	First approved RTK inhibitor
Erlotinib	EGFR	Non-small cell lung cancer, Pancreatic cancer	Used in combination with gemcitabine for pancreatic cancer
Sunitinib	VEGFR, PDGFR	Renal cell carcinoma, Gastrointestinal stromal tumor	Multi-targeted RTK inhibitor
Gefitinib	EGFR	Non-small cell lung cancer	First EGFR inhibitor approved
Sorafenib	VEGFR, RAF kinase	Hepatocellular carcinoma, Renal cell carcinoma	Also inhibits RAF kinases
Lapatinib	HER2/neu, EGFR	Breast cancer	Used in combination with capecitabine