Quick Definition
What is BCRP (Breast Cancer Resistance Protein / ABCG2)?: BCRP (Breast Cancer Resistance Protein), encoded by the ABCG2 gene, is an ABC efflux half-transporter expressed at the intestinal epithelium, blood-brain barrier, liver, kidney, and placenta. It limits oral bioavailability, restricts CNS penetration, and confers multidrug resistance in cancer. Along with P-gp, BCRP is one of two mandatory DDI transporter targets for all NMEs under FDA, EMA, and ICH M12 guidance.
BCRP vs P-gp — key differences
BCRP and P-gp share overlapping but distinct substrate profiles. Several drugs are substrates of both (topotecan, imatinib, gefitinib) — additive efflux limitation at the intestinal barrier. Clinical co-administration of dual BCRP/P-gp inhibitors causes the largest DDI effects due to simultaneous inhibition of both pathways.
In vitro BCRP assessment
Substrate: cell-based bidirectional transport (MDCKII-BCRP) — preferred for low-permeability compounds. Inhibitor IC50: vesicular transport assay with HEK293-BCRP inside-out vesicles — preferred for high-permeability compounds where cell-based efflux ratio is compressed.
Key Facts
- Encoded by ABCG2 — 'half transporter' that forms homodimers to create a functional efflux pump
- Expression: intestinal epithelium (apical), blood-brain barrier (luminal), hepatocyte canalicular membrane, renal proximal tubule, placenta, breast tissue
- Major substrates: rosuvastatin, sulfasalazine, methotrexate, imatinib, topotecan, mitoxantrone, uric acid
- Key inhibitors: fumitremorgin C (FTC, selective in vitro), Ko143, elacridar, gefitinib
- FDA, EMA and ICH M12 require BCRP substrate and inhibitor assessment for all NMEs
- Cutoff: intestinal [I]/IC50 ≥ 0.1 or systemic Cmax,u/IC50 ≥ 0.02 triggers clinical DDI study requirement
- ABCG2 Q141K polymorphism (common in Asian populations ~30% allele frequency) reduces uric acid excretion → 2–3× gout risk
Further Reading
- What is P-glycoprotein (P-gp)?
- What is BSEP?
- FDA & EMA Mandatory Transporters for IND
- Vesicular vs Cell-Based vs ATPase Assay
SeamlessBio GmbH · Passau, Germany · info@seamlessbio.de
English 
Deutsch