An insight into advances and challenges in the development of potential stearoyl Co-A desaturase 1 inhibitors

Stearoyl-CoA desaturase 1 (SCD1) is one of the key enzymes involved in lipid metabolism, plays a vital role in the synthesis of monounsaturated fatty acids (MUFAs) from saturated fatty acids (SFAs). Due to its promising therapeutic potential in treating metabolic disorders, cancers, and skin diseases there is an increasing interest in the development of novel inhibitors against SCD1. This review comprehensively explores the evolution of potential SCD1 inhibitors, focusing on systemic and liver-targeted inhibitors and discusses their structure-activity relationship (SAR) pattern. Among the various small molecules reported, natural products like sterculic acid have emerged as significant SCD1 inhibitors, highlighting the potential of naturally derived compounds in therapeutic development. This review also addresses the challenges in optimizing pharmacokinetic properties and reducing adverse effects, providing insights into the future directions for the development of potential novel SCD1 inhibitors with maximum therapeutic effect and minimum side effects.