CMP25, a synthetic new agent, targets multidrug resistance-associated protein 7 (MRP7/ABCC10).

Antineoplastic Agents / administration & dosage Cell Survival / drug effects Drug Delivery Systems Drug Resistance, Neoplasm / drug effects Drug Therapy, Combination Gene Expression Regulation / drug effects HEK293 Cells Humans Models, Molecular Molecular Dynamics Simulation Molecular Structure Multidrug Resistance-Associated Proteins / antagonists & inhibitors Protein Conformation
1,2,3-Triazole-pyrimidine hybrid ABC transporters ABCC10 MRP7 Multidrug resistance

Journal

Biochemical pharmacology
ISSN: 1873-2968
Titre abrégé: Biochem Pharmacol
Pays: England
ID NLM: 0101032

Informations de publication

Date de publication:
08 2021
Historique:
received: 13 05 2021
revised: 08 06 2021
accepted: 08 06 2021
pubmed: 15 6 2021
medline: 18 11 2021
entrez: 14 6 2021
Statut: ppublish

Résumé

Multidrug resistance-associated protein 7 (MRP7) is an important member of ABC transporter superfamily and has been revealed to mediate the cross-membrane translocation of a wide range of chemotherapeutic agents including taxanes, epothilones, Vinca alkaloids, Anthracyclines and Epipodophyllotoxins.In our previous study, a 1,2,3-triazole-pyrimidine hybridCMP25was synthesized and found able to efficiently reverse multidrug resistance (MDR) mediated by P-glycoprotein. In this study, we evaluated the efficacy of compound CMP25in reversing MDR mediated by MRP7in vitro. The results showed that CMP25significantly sensitized MRP7-overexpressing cells to anticancer drugs that are MRP7 substrates. Mechanistic study showed that CMP25reversed MRP7-mediated MDR by increasing the intracellular accumulation of anticancer drugs and decreasing drug efflux, without altering protein expression level or subcellular localization. Currently, very few studies on synthetic MRP7 modulators have been published. Our findings provide a valuable prototype for designing drugs to combine with conventional anticancer drugs to overcome MDR-mediated by MRP7.

Identifiants

DOI: 10.1016/j.bcp.2021.114652 PMID: 34126072
pubmed: 34126072
pii: S0006-2952(21)00265-3
doi: 10.1016/j.bcp.2021.114652
pii:
doi:

Substances chimiques

ABCC10 protein, human 0
Antineoplastic Agents 0
Multidrug Resistance-Associated Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

114652

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Auteurs

Jing-Quan Wang (JQ)

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.

Bo Wang (B)

Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, PR China; Key Laboratory of Henan Province for Drug Quality and Evaluation, PR China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China.

Qiu-Xu Teng (QX)

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.

Zi-Ning Lei (ZN)

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.

Yi-Dong Li (YD)

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.

Zhi Shi (Z)

Department of Cell Biology & Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong 510632, PR China.

Li-Ying Ma (LY)

Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, PR China; Key Laboratory of Henan Province for Drug Quality and Evaluation, PR China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China.

Hong-Min Liu (HM)

Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, PR China; Key Laboratory of Henan Province for Drug Quality and Evaluation, PR China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China. Electronic address: liuhm@zzu.edu.cn.

Zhijun Liu (Z)

Department of Medical Microbiology, Weifang Medical University, Weifang 261053, PR China. Electronic address: zhijun.liu@wfmc.edu.cn.

Zhe-Sheng Chen (ZS)

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA. Electronic address: chenz@stjohns.edu.

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Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › CMP25, a synthetic new agent, targets...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Survie cellulaire › CMP25, a synthetic new agent, targets...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Systèmes de délivrance de médicaments › CMP25, a synthetic new agent, targets...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Résistance aux médicaments antinéoplasiques › CMP25, a synthetic new agent, targets...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Association de médicaments › CMP25, a synthetic new agent, targets...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › CMP25, a synthetic new agent, targets...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › CMP25, a synthetic new agent, targets...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › CMP25, a synthetic new agent, targets...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles moléculaires › CMP25, a synthetic new agent, targets...
questionsmedicales.fr › Sciences de l'information › Méthodologies informatiques › Simulation numérique › Simulation de dynamique moléculaire › CMP25, a synthetic new agent, targets...
questionsmedicales.fr › Phénomènes chimiques › Structure moléculaire › CMP25, a synthetic new agent, targets...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Pompes ioniques › Transporteurs d'anions › Transporteurs d'anions organiques › Transporteurs d'anions organiques ATP-dépendants › Protéines associées à la multirésistance aux médicaments › CMP25, a synthetic new agent, targets...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › CMP25, a synthetic new agent, targets...