KSTi prodrug

KSTi prodrug is a novel small-molecule prodrug designed to inhibit the lysine succinyltransferase (KSTase) activity of carnitine palmitoyltransferase 1A (CPT1A). While CPT1A is classically known as a rate-limiting enzyme in mitochondrial fatty acid oxidation (FAO), it also exhibits moonlight enzymatic activity as a KSTase. CPT1A-mediated KSTase activity directly succinylates and stabilizes fatty acid synthase (FASN), thereby promoting de novo lipogenesis (DNL) and the accumulation of saturated fatty acids like palmitate, which can impair T-cell function. By inhibiting FASN succinylation and expression, KSTi prodrug reduces intracellular palmitate levels without affecting FAO. Developed by researchers at the Mayo Clinic, KSTi prodrug is utilized for the one-time ex-vivo conditioning of chimeric antigen receptor (CAR) T cells (such as anti-BCMA CAR-T cells) during the manufacturing process to enhance their cytotoxicity, cytokine production (including TNF-alpha and IFN-gamma), and in vivo persistence and durability against multiple myeloma.

Other names

KSTase inhibitor prodrugKSTiprodrug of KSTi