Recent Advances in the Development of Fatty Acid Synthase Inhibitors as Anticancer Agents

Area of Science:

• Biochemistry
• Medicinal Chemistry
• Oncology

Background:

• Fatty acid synthase (FASN) is crucial for lipid biosynthesis and is overexpressed in various diseases, notably cancer.
• FASN's role in cancer involves altering cell membrane structure and function through signaling pathways and protein palmitoylation.
• This overexpression makes FASN a promising therapeutic target for developing novel anticancer drugs.

Purpose of the Study:

• To review recent advancements in anticancer drug discovery targeting FASN.
• To provide insights into the medicinal chemistry of small molecule FASN inhibitors.
• To analyze structural requirements for FASN inhibition to guide the development of new drugs.

Main Methods:

• Literature review of FASN inhibitors and their medicinal chemistry.
• Analysis of small molecule inhibitors targeting different FASN enzyme domains.
• Critical evaluation of structural requirements for FASN inhibition.

Main Results:

• Several natural and synthetic FASN inhibitors exist, with varying potencies (e.g., GSK 2194069 at 7.7 nM, platensimycin at 300 nM).
• Most reported FASN inhibitors have not progressed to clinical trials, except for TVB-2640.
• Insights into medicinal chemistry and structural aspects of FASN inhibitors are presented.

Conclusions:

• FASN remains an attractive target for anticancer drug discovery.
• Understanding the medicinal chemistry and structure-activity relationships of FASN inhibitors is key for developing clinically viable drugs.
• Further research into rational drug design can lead to next-generation FASN inhibitors for cancer treatment.