P-glycoprotein (ABCB1) and ATP-binding cassette sub-family G member 2 (ABCG2) (P-gp; ABCG2)

P-glycoprotein and ABCG2 are integral membrane proteins that utilize ATP hydrolysis to actively transport a broad spectrum of structurally diverse substrates, including many drugs, from the intracellular to the extracellular space or into the lumen of cell organelles[1][2][3][5][7]. Both are part of the ABC transporter family, with P-glycoprotein being a full transporter composed of two nucleotide-binding domains (NBDs) and two transmembrane domains (TMDs), while ABCG2 is a half transporter functioning as a homodimer[4][5]. They are highly promiscuous in substrate recognition, often binding and moving multiple unrelated drugs. Over-expression of either transporter in cancer cells is a well-documented cause of multidrug resistance, limiting the effectiveness of many chemotherapeutic agents. Expression in normal tissues also restricts the absorption or tissue penetration of drugs, protecting sensitive tissues such as the brain.

Other names

Multidrug resistance protein 1MDR1ABCB1PGY1Breast Cancer Resistance ProteinBCRPCDw338

Drugs may act as substrates (transported out of the cell), inhibitors (blocking transporter function to increase intracellular drug accumulation), or modulators (altering transporter ATPase activity)