Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2) (ACSS2)

Acetyl-coenzyme A synthetase, cytoplasmic (ACSS2), also frequently referred to as Acetyl-CoA synthetase 1 (AceCS1), is a critical metabolic enzyme that catalyzes the ATP-dependent conversion of acetate and coenzyme A into acetyl-CoA. It serves as a major source of acetyl-CoA for both cytosolic de novo lipogenesis and nuclear histone acetylation, particularly under conditions of metabolic stress such as hypoxia or nutrient deprivation. In many malignancies, including glioblastoma, breast cancer, and hepatocellular carcinoma, ACSS2 is significantly upregulated, allowing tumor cells to utilize acetate as an alternative carbon source when glucose-derived acetyl-CoA is limited. This metabolic flexibility supports rapid tumor growth, survival, and the epigenetic remodeling necessary for cancer progression. Consequently, ACSS2 has emerged as a promising therapeutic target, with several small-molecule inhibitors currently in preclinical development aimed at disrupting the metabolic and transcriptional adaptations of cancer cells.

Other names

Acetyl-CoA synthetase 1AceCS1ACS1Acyl-CoA synthetase short-chain family member 2Acetate--CoA ligaseAcetyl-activating enzyme

Inhibition of ACSS2 enzymatic activity to prevent the conversion of acetate to acetyl-CoA, thereby disrupting lipid synthesis and epigenetic signaling in cancer cells.