Advancement of Structure-Activity Relationship of Multidrug Resistance-Associated Protein 2 Interactions
Journal Title: The AAPS Journal - Year 2009, Vol 11, Issue 3
Abstract
Multidrug resistance-associated protein 2 (MRP2/ABCC2) is mainly expressed in the apical phase of barrier membranes. It functions as a critical efflux pump in the biliary excretion of endogenous substances, such as conjugated bilirubin and bile salts, as well as many structurally diverse xenobiotics and their metabolites. Due to its important role in defining ADME/Tox properties, efforts have emerged to build the structure–activity relationship (SAR) for MRP2/ABCC2 at early stages of drug discovery process. MRP2/ABCC2 is a member of the integral membrane protein family whose high-resolution crystal structure has not been described. To overcome the obstacle of lacking detailed structural depiction, various molecular modeling approaches have been applied to derive the structural requirements for binding interactions with MRP2/ABCC2 protein, including two-dimensional (2D) and three-dimensional (3D) quantitative SAR (QSAR) analysis, pharmacophore models, and homology modeling of the transporter. Here we summarize recent progresses in understanding the SAR of MRP2/ABCC2 recognition of substrates and/or inhibitors, and describe some of the useful in vitro tools for characterizing the interactions with the transporter.
Authors and Affiliations
Li Xing, Yiding Hu, Yurong Lai
Keywords
Related Articles
- EP ID EP681494
- DOI 10.1208/s12248-009-9117-0
- Views 57
- Downloads 0
Therapeutic Paint of Cidofovir/Sucralfate Gel Combination Topically Administered by Spraying for Treatment of orf virus Infections
The aim of the research was to study a new cidofovir/sucralfate drug product to be used as a spray for treating the mucosal and/or skin lesions. The product, i.e., a water suspension of sucralfate (15% w/w) and cidofovir...
Molecular Mechanisms of Silibinin-Mediated Cancer Chemoprevention with Major Emphasis on Prostate Cancer
Despite advances in early detection, prostate cancer remains the second highest cancer mortality in American men, and even successful interventions are associated with enormous health care costs as well as prolonged dele...
Blood pressure as an example of a biomarker that functions as a surrogate
There are many important uses of biomarkers in drug development. An area of particular interest is the use of biomarkers as surrogate end points. Only a small minority of biomarkers are established surrogate end points....
How to Regulate Nonbiological Complex Drugs (NBCD) and Their Follow-on Versions: Points to Consider
The aim of this critical review is to reach a global consensus regarding the introduction of follow-on versions of nonbiological complex drugs (NBCD). A nonbiological complex drug is a medicinal product, not being a biol...
Nanoparticles Containing Anti-inflammatory Agents as Chemotherapy Adjuvants: Optimization and In Vitro Characterization
The pre-administration of dexamethasone (DEX) has previously been shown to enhance the anti-tumor efficacy of chemotherapeutic agents. The delivery of anti-inflammatory agents specifically to tumors via nanoparticle carr...