TY - JOUR
T1 - About P-glycoprotein
T2 - a new drugable domain is emerging from structural data
AU - Ferreira, Ricardo J.
AU - Bonito, Cátia A.
AU - Ferreira, Maria José U.
AU - dos Santos, Daniel J.V.A.
N1 - Publisher Copyright:
© 2017 John Wiley & Sons, Ltd
PY - 2017/9/1
Y1 - 2017/9/1
N2 - P-glycoprotein (P-gp) has been considered an important molecular target in the reversal of multidrug resistance (MDR). As such, the development of P-gp modulators able to restore drug sensitivity in resistant cells is still considered one of the most promising strategies for overcoming MDR. Since the identification of the P-gp's role in MDR, several studies have been performed in order to develop effective P-gp modulators and understand the efflux mechanism. However, no efflux modulator is still clinically available for treating multidrug-resistant cancers. Nevertheless, recent experimental studies suggest that MDR can be surpassed by targeting a specific region within the ABC transporter structure rather than the polyspecific drug-binding pocket. This article will focus on the information available about this new target region and on a brief overview of which scaffolds would be suitable for modulating P-gp at this new location. WIREs Comput Mol Sci 2017, 7:e1316. doi: 10.1002/wcms.1316. For further resources related to this article, please visit the WIREs website.
AB - P-glycoprotein (P-gp) has been considered an important molecular target in the reversal of multidrug resistance (MDR). As such, the development of P-gp modulators able to restore drug sensitivity in resistant cells is still considered one of the most promising strategies for overcoming MDR. Since the identification of the P-gp's role in MDR, several studies have been performed in order to develop effective P-gp modulators and understand the efflux mechanism. However, no efflux modulator is still clinically available for treating multidrug-resistant cancers. Nevertheless, recent experimental studies suggest that MDR can be surpassed by targeting a specific region within the ABC transporter structure rather than the polyspecific drug-binding pocket. This article will focus on the information available about this new target region and on a brief overview of which scaffolds would be suitable for modulating P-gp at this new location. WIREs Comput Mol Sci 2017, 7:e1316. doi: 10.1002/wcms.1316. For further resources related to this article, please visit the WIREs website.
UR - http://www.scopus.com/inward/record.url?scp=85018777656&partnerID=8YFLogxK
U2 - 10.1002/wcms.1316
DO - 10.1002/wcms.1316
M3 - Review article
AN - SCOPUS:85018777656
SN - 1759-0876
VL - 7
JO - Wiley Interdisciplinary Reviews: Computational Molecular Science
JF - Wiley Interdisciplinary Reviews: Computational Molecular Science
IS - 5
M1 - e1316
ER -