TARGETING HUMAN FATTY ACID SYNTHASE IN CANCER THERAPY: STRUCTURAL INSIGHTS AND SAR OF DOMAIN SPECIFIC INHIBITOR

Fatty acid synthase is a key enzyme in humans that drives the biosynthesis of lipids essential for energy storage and cell membrane formation. Upregulation of FAS is significantly seen in cancer cells due to increased demands of lipids and cell proliferation. Cancer cells rely heavily on fatty acid synthesis to sustain their growth and maintain their malignant characteristics. Over the past two decades, FAS has gained considerable attention as a potential target for cancer therapy, as inhibiting this enzyme could disrupt lipid biosynthesis and impair cancer cell viability. Among the various inhibitors developed so far, TVB-2640 is the only one that has advanced into clinical trials. Here we discuss in detail about the structure and function of various domains of human fatty acid synthase enzyme with its inhibitors. In this review detailed of inhibitors for each domain are discussed. Review highlights how specific modifications to the inhibitor structure can enhance their binding affinity and selectivity towards each domain of FAS. By focusing on the Structural Activity Relationship, we aim to offer insights into the rational design of novel inhibitors that can effectively target FAS in cancer cells, thereby providing new avenues for cancer therapy.