Review
Biochemistry & Molecular Biology
Peter Szatmari, Eszter Ducza
Summary: ABC transporters are essential for drug efflux in the human body, with significant impact on pharmacokinetics and pharmacologic properties of drugs. P-gp and BCRP transporters, in particular, play a crucial role in barrier tissues. During pregnancy, placental and intestinal ABC transporters are of great importance for drug absorption and distribution. Their expression changes with gestational age and can affect the efficacy of various therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Sahar A. Harby, Nehal A. Khalil, Norhan S. El-Sayed, Eman H. Thabet, Samar R. Saleh, Mona Hassan Fathelbab
Summary: The overexpression of breast cancer resistance protein (BCRP), a blood-brain barrier efflux transporter, hampers the entry of antiepileptic drugs into the brain. Inhibition of BCRP improves the bioavailability and efficacy of lamotrigine, playing an important role in the management of drug-resistant epilepsy.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2023)
Article
Oncology
Yan Zou, Zi'xiang Liu, Yi'nan Zhou, Jing Wang, Qin'yi Xu, Xu'dong Zhao, Zeng'li Miao
Summary: Research has found that TRPC5 and P-gp are upregulated in TMZ-resistant glioblastoma cells, and downregulation of TRPC5 can inhibit P-gp expression and significantly reverse TMZ resistance; TRPC5-siRNA limited the tumor xenograft growth of TMZ-resistant cells in an athymic nude mouse model; in specimens from patients with recurrent glioblastoma, TRPC5 and P-gp are highly expressed.
TRANSLATIONAL ONCOLOGY
(2021)
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
Biochemical Research Methods
Vigneshwaran Namasivayam, Katja Stefan, Katja Silbermann, Jens Pahnke, Michael Wiese, Sven Marcel Stefan
Summary: This study successfully extracted molecular structural features of inhibitors of the model protein family of ATP-binding cassette (ABC) transporters using a feature-driven computer-aided pattern analysis (C@PA) method and expanded the known multitarget modulator landscape of pan-ABC transporter inhibitors.
Article
Pharmacology & Pharmacy
Tingting Zhao, Xuening Li, Yanwei Chen, Jie Du, Xiaodong Chen, Dalong Wang, Liyan Wang, Shan Zhao, Changyuan Wang, Qiang Meng, Huijun Sun, Kexin Liu, Jingjing Wu
Summary: Cancer patients are at high risk of thrombotic diseases, but anticoagulant therapy increases bleeding risks. This study explores the combination safety of rivaroxaban with tyrosine kinase inhibitors (TKIs) and finds significant drug-drug interactions in different combinations. Imatinib increases bleeding risks while sunitinib reduces therapeutic efficacy. Therefore, caution should be exercised in the coadministration of rivaroxaban and TKIs to avoid harmful interactions.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Surabhi Talele, Wenjuan Zhang, Danielle M. Burgenske, Minjee Kim, Afroz S. Mohammad, Sonja Dragojevic, Shiv K. Gupta, Ranjit S. Bindra, Jann N. Sarkaria, William F. Elmquist
Summary: The study examines the restricted brain delivery and efficacy of the ATR inhibitor berzosertib in the treatment of GBM. The active efflux at the blood-brain barrier and high binding affinity to brain tissue result in low free drug concentrations in the brain, with heterogeneous distribution into different regions of the brain and tumor. This limited and uneven brain distribution of berzosertib may significantly impact its therapeutic efficacy in GBM.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Dhanamjai Penta, Priya Mondal, Jagadish Natesh, Syed Musthapa Meeran
Summary: The study demonstrates that diindolylmethane can enhance the efficacy of Centchroman in treating breast cancer by modulating drug efflux transporters, inhibiting cell proliferation, inducing apoptosis, and hindering stemness of cancer cells.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Jessica Chu, Erika Panfen, Linna Wang, Anthony Marino, Xue-Qing Chen, R. Marcus Fancher, Raviraj Landage, Omprakash Patil, Salil Dileep Desai, Devang Shah, Yongjun Xue, Michael Sinz, Hong Shen
Summary: The aim of this study was to evaluate the differences between intestinal and systemic P-gp and BCRP in drug disposition. The results showed that ECD is a potent inhibitor of intestinal P-gp and BCRP. The inhibition potential of ECD towards human and animal P-gp and BCRP was assessed in vitro and in vivo.
PHARMACEUTICAL RESEARCH
(2023)
Article
Materials Science, Multidisciplinary
Mohamed S. Attia, Mohamed T. Elsebaey, Galal Yahya, Hitesh Chopra, Mohammed A. Marzouk, Ahmed Yahya, Ahmed S. Abdelkhalek
Summary: Drug resistance is a major obstacle in the treatment of chronic diseases, and various approaches have been developed to overcome it, including targeting other factors involved in altered pathways or targeting the resistance factors themselves. P-glycoprotein (P-gp) and multidrug resistance proteins are among the most causative factors for drug resistance. This review focuses on the use of pharmaceutical polymers as P-gp inhibitors and discusses how modifying their properties can affect P-gp's function. Various P-gp inhibitors, such as chitosan, Soluplus (R), Poloxamers, polyethylene glycols, dendrimers, anionic gums, sodium alginate, and other functionalized polymers, show promise as drug delivery tools by interfering with P-gp. Additionally, pharmaceutical polymers have been utilized in different therapies due to their exceptional physicochemical properties, enhancing their bioavailability, antimicrobial activity, and anticancer properties.
MATERIALS TODAY COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Rong Yang, Zhenxing Chen, Fuda Xie, Mingxiang Xie, Na Liu, Ziren Su, Jiangyong Gu, Ruizhi Zhao
Summary: The study investigated the inhibitory effect of (+)-borneol and (-)-borneol on P-glycoprotein (Pgp) in reversing mitoxantrone (MTO) resistance. The results showed that both borneol enantiomers could enhance the efficacy of MTO in cancer cells by reducing the protein expression of Pgp and interfering with the binding affinity between MTO and Pgp in the drug-binding pocket. Using molecular docking and dynamics simulations, the study identified key amino acid residues responsible for borneols' ability to reverse MTO resistance through noncompetitive inhibition.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Microbiology
Katy Moore, Nilay Thakkar, Mindy Magee, Heather Sevinsky, Blisse Vakkalagadda, Susan Lubin, Cyril Llamoso, Peter Ackerman
Summary: Fostemsavir is a new drug that effectively prevents HIV-1 from entering host cells. Its metabolism is influenced by certain enzymes, and coadministration with other drugs may affect its concentration. This study evaluates the impact of combining fostemsavir with different antiretroviral drugs, showing that some combinations increase temsavir concentrations while others decrease them. Overall, fostemsavir is well tolerated in various combination regimens and does not require dosage adjustments.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Medicine, Research & Experimental
Jun Wu, Quan Wang, Xiaoqi Dong, Min Xu, Juliang Yang, Xiaoqing Yi, Biao Chen, Xiyuan Dong, Ying Wang, Xiaoding Lou, Fan Xia, Shixuan Wang, Jun Dai
Summary: Nanoparticle drug delivery system (NDDS) offers a solution to drug resistance and side effects in traditional chemotherapy. Py-TPE/siRNA@PMP is a multifunctional polymeric nanoparticle designed to combat resistance and side effects in chemotherapy for ovarian cancer, showing promising therapeutic effects in both in vitro and in vivo experiments.
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
Oncology
Lydia Kuhnert, Robert Kuhnert, Menyhart B. Sarosi, Cathleen Lakoma, Birte K. Scholz, Peter Loennecke, Evamarie Hey-Hawkins, Walther Honscha
Summary: Chemotherapy is often hindered by multidrug resistance, and the inhibition of ABCG2 efflux transporter shows promise in overcoming drug resistance. This study successfully enhanced the affinity of baicalein towards ABCG2 by replacing the phenyl ring with a meta-carborane and adding three methoxy substituents. The modified compound demonstrated significant inhibitory effects on ABCG2-mediated drug resistance and holds potential for the development of efficient ABCG2 inhibitors.
MOLECULAR ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Somanath Kundu, Sandeep Kumar, Avinash Bajaj
Article
Biochemistry & Molecular Biology
Manish Singh, Sandhya Bansal, Somanath Kundu, Priyanshu Bhargava, Ashima Singh, Rajender K. Motiani, Radhey Shyam, Vedagopuram Sreekanth, Sagar Sengupta, Avinash Bajaj
Article
Biochemistry & Molecular Biology
Somanath Kundu, Sandhya Bansal, Kalai Mangai Muthukumarasamy, Chetana Sachidanandan, Rajender K. Motiani, Avinash Bajaj
Article
Biochemistry & Molecular Biology
Manish Singh, Ashima Singh, Somanath Kundu, Sandhya Bansal, Avinash Bajaj
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2013)
Article
Biochemical Research Methods
Vedagopuram Sreekanth, Sandhya Bansal, Rajender K. Motiani, Somanath Kundu, Sravan Kumar Muppu, Tapodhara Datta Majumdar, Kuppusamy Panjamurthy, Sagar Sengupta, Avinash Bajaj
BIOCONJUGATE CHEMISTRY
(2013)
Article
Biochemistry & Molecular Biology
Aashish Sharma, Somanath Kundu, Amarendar M. Reddy, Avinash Bajaj, Aasheesh Srivastava
MACROMOLECULAR BIOSCIENCE
(2013)
Article
Oncology
Somanath Kundu, Mohan S. Nandhu, Sharon L. Longo, John A. Longo, Shawn Rai, Lawrence S. Chin, Timothy E. Richardson, Mariano S. Viapiano
Summary: DLG5 is upregulated in malignant gliomas and promotes invasion, viability, and self-renewal of glioblastoma stem cells. It regulates Sonic Hedgehog (Shh) signaling, making DLG5-deficient cells insensitive to Shh ligand, and its loss increases the proteasomal degradation of Gli1, leading to tumor stem cell sensitization. These findings reveal a novel and pro-tumoral role for DLG5 in glioblastoma, distinct from its proposed tumor-suppressor role in other solid tumors.
Article
Oncology
Arivazhagan Roshini, Chandra Goparaju, Somanath Kundu, Mohan S. Nandhu, Sharon L. Longo, John A. Longo, Joan Chou, Frank A. Middleton, Harvey I. Pass, Mariano S. Viapiano
Summary: Fibulin-3 is upregulated in malignant pleural mesothelioma (MPM) tissue and promotes malignant behavior of MPM cells. Targeting fibulin-3 can reduce tumor progression and improve prognosis.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Dimitrius Tansini Pramio, Felipe Monteleone Vieceli, Elisa Varella-Branco, Carolina Purcell Goes, Gerson Shigeru Kobayashi, Diogo Vieira da Silva Pelegrina, Beatriz Caroline de Moraes, Aicha El Allam, Bony De Kumar, Gabriel Jara, Jose Marcelo Farfel, David Alan Bennett, Somanath Kundu, Mariano S. Viapiano, Eduardo Moraes Reis, Paulo Sergio Lopes de Oliveira, Maria Rita dos Santos Passos-Bueno, Carla V. Rothlin, Sourav Ghosh, Deborah Schechtman
Summary: This study identified an epigenetic mechanism regulating the expression of Protein kinase M zeta (PKMζ) in the human brain. DNA methylation at the internal promoter and CREB binding were found to play a critical role in PKMζ expression and its function in neuronal differentiation and Alzheimer's disease.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2023)
Editorial Material
Pharmacology & Pharmacy
Ramanathan Srinivasan, Xiangmin Lin, Natarajan Suganthy, Balakrishnan Shanmuganathan, Kundu Somanath
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Sai Giridhar Sarma Kandanur, Somanath Kundu, Christian Cadena, Homero San Juan, Avinash Bajaj, Juan David Guzman, Srinivas Nanduri, Nageswara Rao Golakoti