Stearoyl-CoA desaturase 1 (SCD1) (SCD1)

Stearoyl-CoA desaturase 1 (SCD1) is a critical endoplasmic reticulum-anchored enzyme that catalyzes the rate-limiting step in the biosynthesis of monounsaturated fatty acids (MUFAs) from saturated fatty acids (SFAs). By introducing a cis-double bond at the delta-9 position of substrates such as stearoyl-CoA and palmitoyl-CoA, SCD1 regulates the cellular ratio of MUFAs to SFAs, which is essential for maintaining membrane fluidity, energy storage, and lipid-mediated signaling. High expression of SCD1 is strongly associated with metabolic disorders, including obesity, insulin resistance, and non-alcoholic steatohepatitis (NASH), as well as various malignancies where it supports rapid cell proliferation and survival. Consequently, SCD1 has emerged as a significant therapeutic target, with several small-molecule inhibitors like Aramchol and MK-8245 undergoing clinical evaluation for metabolic and oncological indications. However, systemic inhibition of SCD1 is often limited by mechanism-based adverse effects, such as severe skin and eye toxicities (e.g., alopecia and dry eyes), which result from the depletion of MUFAs required for sebaceous gland function. To overcome these challenges, current research focuses on developing tissue-selective or liver-targeted inhibitors to improve the therapeutic window and minimize off-target inflammatory responses.

Other names

Acyl-CoA desaturase 1Delta(9)-desaturase 1Fatty acid desaturase 1hSCD1SCD

Inhibition of delta-9 fatty acid desaturase activity to reduce the conversion of saturated fatty acids into monounsaturated fatty acids.