Gefitinib

Gefitinib is a potent, orally bioavailable inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. It selectively binds to the ATP-binding site of EGFR, blocking autophosphorylation and downstream signaling pathways involved in cell proliferation, survival, and angiogenesis. Gefitinib exhibits nanomolar potency with IC₅₀ values ranging from 26 to 57 nM depending on the assay system, making it a valuable tool in cancer research and targeted therapy development.

Key features and applications include:

• Highly Selective EGFR Inhibition: Gefitinib specifically targets EGFR tyrosine kinase activity, reducing off-target effects and enhancing therapeutic precision.
• Mechanistic Studies: Widely used to dissect EGFR-mediated signaling pathways, including PI3K/AKT/mTOR and RAS/RAF/MEK/ERK cascades.
• Cancer Cell Line Research: Demonstrates strong anti-proliferative effects in EGFR-overexpressing cell lines, inducing G1 cell cycle arrest and apoptosis.
• Combination Therapy Research: Frequently studied in combination with mTOR inhibitors, chemotherapy agents, or radiation to overcome resistance and enhance efficacy.
• Autophagy and Apoptosis Studies: Used to explore mechanisms of programmed cell death and survival signaling in tumor cells.
• Angiogenesis Inhibition: Suppresses VEGF expression and tumor vascularization, contributing to its anti-tumor effects.

Relevant disease states include:

• Non-Small Cell Lung Cancer (NSCLC): Gefitinib is FDA-approved for first-line treatment of NSCLC patients with activating EGFR mutations (e.g., exon 19 deletions, L858R).
• Triple-Negative Breast Cancer (TNBC): Investigated for its potential to sensitize TNBC cells to other targeted therapies.
• Colorectal and Head & Neck Cancers: Studied for its ability to inhibit EGFR-driven tumor growth and resistance mechanisms.
• Glioblastoma and Brain Tumors: Explored for its ability to cross the blood-brain barrier and inhibit EGFR in glioma models.