Multidrug resistance protein 1 (MRP1/ABCC1) is an ATP-dependent efflux transporter, and responsible for the transport of a broad spectrum of xenobiotics, toxins, and physiological substrates across the plasma membrane. As an efflux pump, it plays a significant role in the absorption and disposition of drugs including anticancer drugs, antivirals, antimalarials, and antibiotics and their metabolites across physiological barriers in cells. MRP1 is also known to aid in the regulation of several physiological processes such as redox homeostasis, steroid metabolism, and tissue defense. However, its overexpression has been reported to be a key clinical marker associated with multidrug resistance (MDR) of several types of cancers including lung cancer, childhood neuroblastoma, breast and prostate carcinomas, often resulting in a higher risk of treatment failure and shortened survival rates in cancer patients. Aside MDR, overexpression of MRP1 is also implicated in the development of neurodegenerative and cardiovascular diseases. Due to the cellular importance of MRP1, the identification and biochemical/molecular characterization of modulators of MRP1 activity and expression levels are of key interest to cancer research and beyond. This review primarily aims at highlighting the physiological and pharmacological importance of MRP1, known MRP1 modulators, current challenges encountered, and the potential benefits of conducting further research on the MRP1 transporter.

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The Multidrug Resistance Associated Protein 1 is a key feature in drug resistance within cancerous cells. This protein is involved in efflux of a broad spectrum of substrates, including organic anions and several chemical therapeutic agents, like doxorubicin. In addition, MRP1 has implications in separate physiologies such as cardiovascular disease and age‐related macular degradation. As such, its overexpression has been implicated in multidrug resistance of several cancers. This project is aimed at evaluating the effect of chemotherapeutic agents on the expression levels of MRP1 in HEK293/MRP1 cells. A unique library of FDA drugs were screened using a high throughput In‐Cell ELISA Assay. A total of 88 drugs were screened. Drugs that showed modulation of MRP1 protein expression above 30% were considered as Hit compounds. A significant number of hits were identified, from which some of the drugs increased MRP1 protein expression and decreased its expression. This protein enhances the cells ability to efflux toxic compounds, such as anticancer drugs, out of the cell. A cell’s ability to increase expression of this protein results from a genetic mutation. As a result, higher concentrations of traditional anticancer drug compounds are required to demonstrate similar results as cells that do not over express MRP1. However, discovery of drugs that can decrease the expression of this protein would play a valuable role in assisting the fight against cancer. Support or Funding Information I would like to thank Jack and Mary East for their support and funding for this project