Role of heterocycles in inhibition of VEGFR-2 - a recent update (2019-2022)

Area of Science:

• Oncology
• Medicinal Chemistry
• Pharmacology

Background:

• Oncogenic protein kinase inhibition is a validated anticancer strategy.
• Vascular Endothelial Growth Factor Receptor (VEGFR) signaling, particularly VEGFR-2, is crucial for tumor angiogenesis and metastasis.
• VEGFRs are implicated in various diseases, making their inhibition a therapeutic target.

Purpose of the Study:

• To review research on small molecular heterocycle-based VEGFR-2 inhibitors.
• To discuss the structure-activity relationships of these inhibitors.
• To identify potent VEGFR inhibitors and their structural features for improved cancer therapy design.

Main Methods:

• Literature review of studies focusing on VEGFR inhibitory activity.
• Analysis of structure-activity relationships for designed heterocycle-based molecules.
• Identification of potent VEGFR inhibitors and their key structural determinants.

Main Results:

• Small molecular heterocycle-based VEGFR-2 inhibitors have been developed, with some FDA-approved.
• Existing inhibitors can cause adverse effects like cardiovascular issues and renal impairment.
• Combinations of specific pharmacophores, particularly heterocycles, enhance VEGFR inhibitory activity.

Conclusions:

• VEGFR-2 inhibitors are a significant area of cancer research.
• Combination strategies involving heterocycles show potential for developing more effective and safer VEGFR inhibitors.
• Understanding structure-activity relationships is key to designing next-generation VEGFR inhibitors for cancer treatment.