Copper transport protein 1 (CTR1) (CTR1)

Copper transport protein 1 (CTR1), encoded by the SLC31A1 gene, is the primary high-affinity transporter responsible for the influx of copper ions across the plasma membrane into the cytoplasm (UniProt: O15431). It is essential for maintaining copper homeostasis, which supports the activity of vital cuproenzymes involved in energy production, iron metabolism, and antioxidant defense (PubMed: 21339183). In clinical oncology, CTR1 is a critical determinant of the efficacy of platinum-based chemotherapy, as it serves as a major gateway for the entry of drugs like cisplatin and carboplatin into tumor cells (PubMed: 12023331). Reduced expression of CTR1 is frequently associated with the development of platinum resistance, making it a target for strategies aimed at modulating drug uptake (PubMed: 16166297). Beyond cancer, the broader copper transport system, including the efflux transporters ATP7A and ATP7B, is implicated in genetic disorders such as Menkes and Wilson diseases (NIH: GeneReviews). In these conditions, impaired transport leads to systemic copper deficiency or toxic accumulation, respectively, requiring therapeutic intervention with copper supplements or chelators (PubMed: 23535945). Emerging research also links copper transport dysregulation to neurodegenerative diseases like Alzheimer's, where copper-mediated oxidative stress plays a role (PubMed: 22524482). Drugs like tetrathiomolybdate are being investigated for their ability to inhibit CTR1 and reduce copper levels in both Wilson disease and certain cancers (PubMed: 15623864).

Other names

Solute carrier family 31 member 1SLC31A1High affinity copper uptake protein 1COPT1Copper ion transport across cellular membranes (biological process)

The primary mechanism of action for drugs interacting with this target involves serving as substrates for facilitated transport into cells, as seen with platinum-based chemotherapeutics like cisplatin (PubMed: 12023331). Other agents, such as tetrathiomolybdate, act by inhibiting the transporter or its associated chaperones to reduce copper uptake (PubMed: 15623864). Additionally, chelating agents like penicillamine and trientine lower the availability of copper ions for transport, thereby managing conditions of copper overload (NIH: GeneReviews).