Cystine and thiol–disulfide transporters (HATs)

The term Cystine and thiol–disulfide substrates refers to a functional classification of transporters within the Solute Carrier (SLC) family that mediate the movement of cystine and related thiol-disulfide molecules across cellular membranes (IUPHAR/BPS Guide to PHARMACOLOGY). This group primarily includes the heteromeric amino acid transporters (HATs) System xc- (composed of SLC7A11 and SLC3A2) and System b0,+ (composed of SLC7A9 and SLC3A1). System xc- is a critical therapeutic target in oncology and neurology because it exchanges extracellular cystine for intracellular glutamate, providing the necessary precursor for glutathione (GSH) synthesis, which protects cells from oxidative stress and ferroptosis (PMID: 33461485). System b0,+ is primarily involved in the renal and intestinal reabsorption of cystine, and its dysfunction leads to cystinuria, a condition characterized by the formation of cystine stones in the urinary tract (PMID: 31105042). Drugs targeting these systems include inhibitors like sulfasalazine and erastin, which induce ferroptosis in cancer cells by depleting GSH, as well as thiol-depleting agents like tiopronin used to manage cystinuria (PubChem). Safety concerns associated with modulating these targets include the potential for systemic oxidative damage and alterations in excitatory neurotransmission due to changes in extracellular glutamate levels (PMID: 31105042).

Other names

System xc-System b0,+Cystine/glutamate transporterSLC7A11SLC7A9xCTrBAT/b0,+ATHeteromeric amino acid transporters (HATs)

Inhibition of cystine uptake to deplete intracellular glutathione and induce ferroptosis; modulation of disulfide exchange to prevent cystine stone formation.