What is a BCRp inhibitor?: A Comprehensive Guide to its Role in Pharmacology

October 14, 2025 •

4 min read

According to research, overexpression of BCRP is associated with clinical multidrug resistance in cancer, a major barrier to effective chemotherapy. A BCRp inhibitor is a compound designed to block this drug efflux pump, thereby increasing the concentration of therapeutic agents inside cancer cells.

Quick Summary

A BCRp inhibitor blocks the Breast Cancer Resistance Protein (BCRP), an efflux pump that expels drugs from cells. Inhibiting BCRP can reverse multidrug resistance in cancer, enhance drug bioavailability, and influence drug-drug interactions.

Key Points

Drug Efflux Pump: BCRP is an ATP-binding cassette (ABC) efflux transporter that pumps drugs and toxins out of cells.
Combating Multidrug Resistance (MDR): BCRP inhibitors are used in cancer treatment to reverse multidrug resistance by keeping chemotherapy drugs inside tumor cells.
Altering Pharmacokinetics: By inhibiting BCRP, these compounds can increase the absorption (bioavailability) and alter the distribution and elimination of co-administered drugs.
Drug-Drug Interactions (DDIs): Inhibiting BCRP can cause significant drug-drug interactions, a major consideration for safety and efficacy, as seen with statins.
Affecting Biological Barriers: BCRP inhibitors can increase a drug's penetration across physiological barriers like the blood-brain barrier (BBB) and placenta.
Research and Development: Developing selective BCRP inhibitors is challenging, requiring a balance between overcoming cancer resistance and avoiding toxicity in healthy tissues.

Understanding BCRP and Efflux Transporters

Breast Cancer Resistance Protein (BCRP), also known as ABCG2, is a member of the large ATP-binding cassette (ABC) transporter superfamily. Found in various tissues throughout the body, it acts as a crucial drug efflux pump that utilizes energy from ATP hydrolysis to actively transport diverse substances, including drugs and xenobiotics, out of cells. BCRP plays a key physiological role by restricting the access of potentially harmful compounds to sensitive organs, such as the brain, testes, and fetus. However, this protective mechanism can be a double-edged sword, as its overexpression in tumor cells is a primary cause of multidrug resistance (MDR) in cancer therapy.

The Function and Impact of a BCRP Inhibitor

A BCRp inhibitor is any compound that can block or reduce the activity of the BCRP transporter. By doing so, it prevents cancer cells from expelling chemotherapeutic drugs, thereby increasing the drug's intracellular concentration and restoring the tumor's sensitivity to treatment. The development of these inhibitors is a significant area of cancer research, as they offer a potential strategy to circumvent drug resistance and improve treatment outcomes.

How BCRP Inhibitors Combat Multidrug Resistance

In many cancers, cells increase their expression of efflux pumps like BCRP as a defense mechanism against chemotherapy. This leads to a phenomenon known as multidrug resistance, where the cancer becomes unresponsive to treatment. BCRP inhibitors act by interfering with this defense, effectively trapping the therapeutic agent inside the malignant cell. This re-sensitization allows the chemotherapy drug to reach its effective concentration and exert its cytotoxic effect, overcoming the resistance that would otherwise render the treatment futile.

Affecting Drug Pharmacokinetics at Physiological Barriers

BCRP's influence extends beyond cancer cells to normal tissues, where it is highly expressed in key barriers, such as:

The small intestine: BCRP limits the absorption of oral drugs, influencing their bioavailability. Inhibition can significantly increase plasma concentrations of co-administered drugs.
The blood-brain barrier (BBB): BCRP prevents many drugs from entering the central nervous system, protecting the brain from toxic substances. BCRP inhibitors can be used to increase brain penetration of certain drugs, a strategy explored for treating brain tumors.
The placenta: BCRP plays a protective role for the fetus by effluxing drugs and toxins away from fetal circulation. Inhibition can weaken this protection, increasing fetal drug exposure.
The liver and kidneys: BCRP aids in the excretion of drugs and metabolites, with its inhibition potentially altering the rate at which they are cleared from the body.

The Challenge of Drug-Drug Interactions

Because BCRP inhibitors can significantly alter the pharmacokinetics of many drugs, they are a major source of potential drug-drug interactions (DDIs). Regulators like the FDA and EMA require new drugs to be tested for their potential to inhibit BCRP. For example, the concurrent use of BCRP-inhibiting drugs with statins, like rosuvastatin, can lead to dangerously elevated plasma levels of the statin, increasing the risk of adverse effects.

Overcoming Challenges in Development

Developing selective and safe BCRP inhibitors is complex due to the transporter's widespread expression in both cancerous and healthy tissues. A compound that effectively blocks BCRP in tumor cells must also be engineered to minimize off-target toxicity in normal barrier tissues, particularly the brain. This is a major focus of ongoing research and involves carefully balancing efficacy with safety.

Comparison of BCRP Inhibitors and Modulators

Here is a comparison of some well-known BCRP inhibitors and modulators, highlighting their characteristics and uses:


Inhibitor Name	Source	Specificity	Status/Use	Notes
Fumitremorgin C (FTC)	Natural compound	High specificity for BCRP	Research tool	Potent and specific inhibitor often used in in vitro studies.
Elacridar (GF120918)	Synthetic compound	Dual P-gp/BCRP inhibitor	Clinical stage (investigational)	Increases oral bioavailability and brain penetration of co-administered drugs.
Curcumin	Natural compound (turmeric)	Non-specific inhibitor	Dietary supplement / Research	A natural compound shown to inhibit BCRP and potentially reverse MDR in lab settings.
Vemurafenib	Small molecule	Strong BCRP inhibitor	FDA-approved drug (melanoma)	Primarily a BRAF inhibitor, but also found to have strong BCRP inhibitory activity.

Conclusion: The Future of BCRp Inhibition

In summary, a BCRp inhibitor is a pharmacological agent that targets the BCRP efflux pump. These inhibitors are crucial tools for modern medicine, particularly in the fight against cancer. By reversing multidrug resistance, they have the potential to significantly enhance the efficacy of chemotherapy and other therapeutic agents. However, the development of safe and selective BCRP inhibitors remains a challenge, as their impact on physiological barriers and potential for drug-drug interactions must be carefully managed. Ongoing research in this field promises to yield new strategies for optimizing drug delivery and overcoming a significant obstacle in cancer treatment.

Frequently Asked Questions

BCRP, or ABCG2, is an energy-dependent drug efflux pump protein. It expels a wide range of substances, including chemotherapy drugs and toxins, from cells, which helps protect the body but can also lead to drug resistance.

In cancer, BCRP is often overexpressed and pumps chemotherapy drugs out of tumor cells, causing them to become resistant to treatment. A BCRP inhibitor blocks this efflux action, allowing the chemotherapy drug to accumulate inside the cancer cell and kill it.

Since BCRP is present in normal tissues like the brain, gut, and placenta, inhibiting it can increase the concentration of drugs in these areas, potentially causing toxicity. For example, blocking BCRP at the blood-brain barrier could lead to neurotoxicity.

Yes, BCRP and P-glycoprotein (P-gp) often work together at the blood-brain barrier to restrict drug entry into the brain. Inhibiting these transporters is a strategy being investigated to increase the brain penetration of anticancer drugs for treating brain tumors.

A specific BCRP inhibitor, like fumitremorgin C, targets BCRP with high selectivity, while a non-specific inhibitor, such as curcumin or some tyrosine kinase inhibitors, can also block other transporters like P-gp.

Because BCRP influences the absorption, distribution, and elimination of many drugs, its inhibition can cause clinically significant drug-drug interactions. For instance, co-administering a BCRP inhibitor with a statin like rosuvastatin can dramatically increase the statin's exposure.

While compounds with BCRP inhibitory activity exist (e.g., some tyrosine kinase inhibitors), there is currently no clinically available substance whose primary purpose is to be a BCRP inhibitor. Many are used as research tools or have other primary functions.