Multidrug resistance proteins (MRPs)

Multidrug resistance proteins (MRPs/ABCCs) are ATP-binding cassette export pumps that transport anionic compounds, including glutathione, glucuronide, and sulfate conjugates^[1]. Mechanistically, MRP1 and MRP2 mediate ATP-dependent export of leukotriene C₄, bilirubin glucuronides, 17β-glucuronosyl estradiol, and glutathione disulfide, linking detoxification with oxidative-stress defense^[1]. In tumor models, MRP overexpression increases ATP-dependent glutathione S-conjugate transport and supports multidrug resistance by exporting drug modification products from cancer cells^[2]. Compared with MDR1 P-glycoprotein, MRP1 and MRP2 show distinct substrate specificity and function as conjugate-transporting ATPases rather than broad neutral-drug pumps^[1]. Isoform distinction is central: MRP1 occurs in many plasma membranes, whereas MRP2 localizes apically in polarized epithelia, including hepatocyte canalicular and kidney proximal tubule luminal membranes^[1]. MRP4 differs further because it transports cyclic nucleotides, steroid conjugates, bile acid conjugates, arsenic metabolites, and paracetamol glutathione or cysteine conjugates in defined experimental systems^[3]^[4]^[5]. For research applications, MK571 inhibits MRP-associated glutathione S-conjugate transport, while glutathione-conjugated catechol metabolites and registered oral drugs modulate MRP1 or MRP2 transport activity in vesicle assays^[6]^[7]^[8].

References:

[1]. Keppler D, et al. ATP-dependent transport of glutathione S-conjugates by the multidrug resistance protein MRP1 and its apical isoform MRP2. Chem Biol Interact. 1998 Apr 24;111-112:153-61.

[2]. Müller M, et al. Overexpression of the gene encoding the multidrug resistance-associated protein results in increased ATP-dependent glutathione S-conjugate transport. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):13033-7.

[3]. Zelcer N, et al. Steroid and bile acid conjugates are substrates of human multidrug-resistance protein (MRP) 4 (ATP-binding cassette C4). Biochem J. 2003 Apr 15;371(Pt 2):361-7. [Content Brief]

[4]. Banerjee M, et al. A novel pathway for arsenic elimination: human multidrug resistance protein 4 (MRP4/ABCC4) mediates cellular export of dimethylarsinic acid (DMAV) and the diglutathione conjugate of monomethylarsonous acid (MMAIII). Mol Pharmacol. 2014 Aug;86(2):168-79.

[5]. Koenderink JB, et al. Human multidrug resistance protein 4 (MRP4) is a cellular efflux transporter for paracetamol glutathione and cysteine conjugates. Arch Toxicol. 2020 Sep;94(9):3027-3032.

[6]. Pulaski L, et al. Identification of the multidrug-resistance protein (MRP) as the glutathione-S-conjugate export pump of erythrocytes. Eur J Biochem. 1996 Oct 15;241(2):644-8.

[7]. Slot AJ, et al. Modulation of human multidrug resistance protein (MRP) 1 (ABCC1) and MRP2 (ABCC2) transport activities by endogenous and exogenous glutathione-conjugated catechol metabolites. Drug Metab Dispos. 2008 Mar;36(3):552-60.

[8]. Pedersen JM, et al. Prediction and identification of drug interactions with the human ATP-binding cassette transporter multidrug-resistance associated protein 2 (MRP2; ABCC2). J Med Chem. 2008 Jun 12;51(11):3275-87.

Multidrug resistance proteins (MRPs) Inhibitor (1)

Multidrug resistance proteins (MRPs) Related Products (1):

Cat. No.	Product Name	Effect	Purity

HY-W010649

Isoxazole	Inhibitor	99.98%
Isoxazole is a member of the five-membered heterocycle drug scaffold. Isoxazole has been used as a BET bromodomain inhibitor and can improve β-cell function in a diabetic mouse model. Isoxazole and its derivatives exhibit broad biological activities (such as antimicrobial, antibacterial, antifungal, antiviral, anticancer, anti-inflammatory, immunomodulatory, analgesic, anti-tuberculosis, and anti-diabetic effects). For example, the bicyclic Isoxazole can act as an HSP90 inhibitor, and the tricyclic Isoxazole is promising as a selective multidrug resistance protein (MRP1) inhibitor.

Name
Email *

	Sorry, but the email address you supplied was invalid.