Article
Chemistry, Medicinal
Laura Braconi, Silvia Dei, Marialessandra Contino, Chiara Riganti, Gianluca Bartolucci, Dina Manetti, Maria Novella Romanelli, Maria Grazia Perrone, Nicola Antonio Colabufo, Stefano Guglielmo, Elisabetta Teodori
Summary: New 2,5- and 1,5-disubstituted tetrazoles, and 2,5-disubstituted-1,3,4-oxadiazoles were synthesized and studied as MDR reversers, showing potent inhibitory effects on P-gp transport activity and increasing the antiproliferative effect of doxorubicin in MDR cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Lei Zhang, Biwei Ye, Yunfeng Lin, Yi-Dong Li, Jing-Quan Wang, Zhuo Chen, Feng-Feng Ping, Zhe-Sheng Chen
Summary: In this study, the researchers investigated the effect of the CDK4/6 inhibitor, ribociclib, on multidrug resistance (MDR) mediated by P-glycoprotein (P-gp) in human epidermoid carcinoma cells. They found that ribociclib increased the efficacy of a P-gp substrate drug, colchicine, by down-regulating the expression of P-gp and increasing its ATPase activity. Docking studies suggested that ribociclib interacted with the drug-substrate binding site of P-gp. Additionally, ribociclib inhibited the drug efflux activity of P-gp, leading to increased intracellular accumulation of doxorubicin. These findings suggest that ribociclib may be a potential agent for combined therapy in cancers with P-gp-mediated MDR.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Chemistry, Medicinal
Hang Zhang, Haiwei Xu, Charles R. Ashby, Yehuda G. Assaraf, Zhe-Sheng Chen, Hong-Min Liu
Summary: This review highlights the recent achievements in drug design and mechanism studies of newly synthetic P-gp inhibitors in the past 5 years, which will help overcome multidrug resistance in cancer chemotherapy.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Pharmacology & Pharmacy
Sai-Qi Wang, Qiu-Xu Teng, Shuai Wang, Zi-Ning Lei, Hui-Hui Hu, Hui-Fang Lv, Bei-Bei Chen, Jian-Zheng Wang, Xiao-Jing Shi, Wei-Feng Xu, Hong-Min Liu, Xiao-Bing Chen, Zhe-Sheng Chen, Bin Yu
Summary: The compound WS-716 based on triazolo[1,5-a]pyrimidine was reported as a highly potent, specific, and orally active P-gp inhibitor against MDR cancer, showing therapeutic promise. WS-716 and PTX synergistically inhibited growth of resistant cells, induced apoptosis, and increased sensitivity of MDR tumors to PTX.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Biochemistry & Molecular Biology
Yasmeen Cheema, Yusra Sajid Kiani, Kenneth J. J. Linton, Ishrat Jabeen
Summary: Researchers developed a pharmacophore model based on the cryo-EM structure of ABCB1 to screen for new inhibitors, resulting in the identification of six potential inhibitors with distinct chemistries and favorable properties. The compounds exhibited low nanomolar range inhibitory concentrations and two of them were able to resensitize ABCB1-expressing cells to taxol. This study demonstrates the utility of cryo-electron microscopy in drug identification and design.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Lina Jia, Xiaoyun Gao, Yi Fang, Haotian Zhang, Lihui Wang, Xing Tang, Jingyu Yang, Chunfu Wu
Summary: TM2, a taxane derivative, shows significant anti-cancer activity against drug-resistant non-small cell lung cancer cells by inhibiting P-gp function and stabilizing microtubule polymerization.
Article
Chemistry, Multidisciplinary
Shi-Jie Hao, Ya-Xuan Zhu, Fu -Gen Wu
Summary: Researchers developed a membrane fusion liposome (MFL) loaded with a small-molecule tyrosine kinase inhibitor (TKI) and doxorubicin (Dox) to achieve tumor cell membrane fusion-mediated drug delivery and enhanced chemotherapy of drug-resistant tumor.
JOURNAL OF CONTROLLED RELEASE
(2023)
Review
Pharmacology & Pharmacy
Sachin Rathod, Heta Desai, Rahul Patil, Jayant Sarolia
Summary: This article discusses the significance of studying P-glycoprotein in drug delivery and highlights the effective reversal of P-gp inhibition using nonionic surfactants. Nonionic surfactants, being inert, non-toxic, and efficient, show potential as P-gp inhibitors and improve drug absorption and bioavailability through various mechanisms.
Article
Pharmacology & Pharmacy
Zhihao Liu, Xiaozhou Wen, Guangji Wang, Ying Zhou
Summary: 23-HBA significantly enhances the efficacy of anti-tumor agents in MDR cells, related to P-gp inhibition. Experimental results demonstrate that 23-HBA can improve cytotoxicity of ADR and VCR in MDR cells and affect the transport of P-gp substrates.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Mahdi Ghadi, Seyed Jalal Hosseinimehr, Fereshteh Talebpour Amiri, Alireza Mardanshahi, Zohreh Noaparast
Summary: P-glycoprotein (P-gp) serves as a vital efflux pump in chemotherapy resistance in human colon cancer. The study demonstrates the synergistic anti-tumor activity of itraconazole and paclitaxel, showing enhanced cytotoxicity and tumor growth suppression. Additionally, Tc-99m-MIBI is identified as an effective radiotracer for monitoring response to treatment in MDR tumors.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Kunal S. Taskar, Xinning Yang, Sibylle Neuhoff, Mitesh Patel, Kenta Yoshida, Mary F. Paine, Kim L. R. Brouwer, Xiaoyan Chu, Yuichi Sugiyama, Jack Cook, Joseph W. Polli, Imad Hanna, Yurong Lai, Maciej Zamek-Gliszczynski
Summary: This article discusses the role of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) in drug-drug interactions, drug absorption, and brain penetration. Based on clinical evidence, the article suggests that inhibition of P-gp or BCRP in the liver or kidneys has limited clinical implications on drug disposition.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Ashutosh Singh, Sandesh Kumar Patel, Prateek Kumar, Kanhu Charan Das, Deepanshu Verma, Rohit Sharma, Timir Tripathi, Rajanish Giri, Natalia Martins, Neha Garg
Summary: The resistance of cancer cells to chemotherapy is a major challenge in drug discovery. P-glycoprotein (P-gp) overexpression is directly linked to multidrug resistance (MDR) in cancer cells. Quercetin has been reported to inhibit the activity of P-gp, but the underlying mechanism is not fully understood. This study reveals the mechanistic understanding of quercetin-induced modulation of P-gp using molecular docking and molecular dynamics simulation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Review
Pharmacology & Pharmacy
Sepideh Mirzaei, Mohammad Hossein Gholami, Farid Hashemi, Amirhossein Zabolian, Mahdi Vasheghani Farahani, Kiavash Hushmandi, Ali Zarrabi, Aaron Goldman, Milad Ashrafizadeh, Gorka Orive
Summary: In this review, the molecular pathways regulating P-gp and its involvement in DOX resistance are highlighted. The development of nanocarriers for co-delivery of DOX with anticancer compounds and genes is also discussed. Furthermore, the surface modification of nanocarriers to enhance selectivity towards cancer cells is explored.
DRUG DISCOVERY TODAY
(2022)
Article
Biochemistry & Molecular Biology
Wenqin Sun, Iris L. K. Wong, Helen Ka-Wai Law, Xiaochun Su, Terry C. F. Chan, Gege Sun, Xinqing Yang, Xingkai Wang, Tak Hang Chan, Shengbiao Wan, Larry M. C. Chow
Summary: Tea polyphenol derivative EC31 is a potent and nontoxic P-gp inhibitor that can reverse multidrug resistance and enhance the efficacy of anticancer drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Liadys Mora Lagares, Yunierkis Perez-Castillo, Nikola Minovski, Marjana Novic
Summary: P-gp is an important protein involved in drug efflux and multidrug resistance. Molecular dynamics simulations can provide valuable insights into the binding behavior and conformational changes of P-gp in the presence of different compounds.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)