Article
Biochemistry & Molecular Biology
Ingrid Fatima Zattoni, Thales Kronenberger, Diogo Henrique Kita, Lais Danciguer Guanaes, Matheus Murmel Guimaraes, Larissa de Oliveira Prado, Melanie Ziasch, Luis C. Vesga, Fabiane Gomes de Moraes Rego, Geraldo Picheth, Marcos Brown Goncalves, Miguel D. Noseda, Diogo R. B. Ducatti, Antti Poso, Robert W. Robey, Suresh Ambudkar, Vivian Rotuno Moure, Alan Guilherme Goncalves, Glaucio Valdameri
Summary: A newly discovered porphyrin derivative (4B) was identified as an inhibitor of the ABCG2 transporter, capable of overcoming multidrug resistance in vitro and showing selective inhibition towards ABCG2 without being transported by it.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Chemistry, Medicinal
Ingrid Fatima Zattoni, Leticia Carani Delabio, Julia de Paula Dutra, Diogo Henrique Kita, Gustavo Scheiffer, Marina Hembecker, Giovana da Silva Pereira, Vivian Rotuno Moure, Glaucio Valdameri
Summary: The primary source of failure in cancer therapies is multidrug resistance (MDR) caused by overexpression of ABC transporters, particularly the breast cancer resistance protein (BCRP/ABCG2). Inhibiting ABCG2 function and modulating its expression are promising strategies to overcome MDR. This review provides an overview of various ABCG2 inhibitors and discusses their chemical aspects, experimental methods used for identification and characterization, as well as the biological requirements for preclinical tests. Additionally, the potential use of ABCG2 inhibitors in cancer stem cells (CSC) to improve treatment response and the mechanism of ABCG2 modulators at the transcriptional and protein expression levels are discussed.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Endocrinology & Metabolism
Nicolas Tournier, Sebastien Goutal, Severin Mairinger, Irene Hernandez-Lozano, Thomas Filip, Michael Sauberer, Fabien Caille, Louise Breuil, Johann Stanek, Anna F. Freeman, Gaia Novarino, Charles Truillet, Thomas Wanek, Oliver Langer
Summary: This study investigated the feasibility of simultaneous inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar. The combination led to increased brain distribution of the model substrate in mice and macaques, potentially enhancing brain delivery of molecularly targeted anticancer drugs for the treatment of brain tumors. Additionally, tolerability and induction of apoptosis were assessed in human cerebral organoids, showing promising results for future applications.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Imen Dakhlaoui, Sahel Vahdati, Emna Maalej, Fakher Chabchoub, Michael Wiese, Jose Marco-Contelles, Lhassane Ismaili
Summary: Multidrug resistance is a major obstacle in successful cancer chemotherapy, driven by ABC transport proteins. This study focused on designing and synthesizing new pyrimidopyrimidines, identifying a promising compound with selective and effective inhibition of ABCG2.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Shoji Kokubo, Shinobu Ohnuma, Megumi Murakami, Haruhisa Kikuchi, Shota Funayama, Hideyuki Suzuki, Taiki Kajiwara, Akihiro Yamamura, Hideaki Karasawa, Norihiko Sugisawa, Kosuke Ohsawa, Kuniyuki Kano, Junken Aoki, Takayuki Doi, Takeshi Naitoh, Suresh V. Ambudkar, Michiaki Unno
Summary: This study identified a novel ABCG2 inhibitor, PFC, through high-throughput screening, which significantly decreased IC50 of SN-38 in cancer cells and reversed resistance to irinotecan without causing toxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Chung-Pu Wu, Sung-Han Hsiao, Yu-Shan Wu
Summary: The overexpression of human ATP-binding cassette (ABC) transporters in cancer cells can lead to multidrug resistance (MDR), which poses a significant obstacle to chemotherapy. Currently, there are no approved drugs specifically designed to treat multidrug-resistant cancers. However, drug repurposing has emerged as a practical approach to discover effective modulators of drug transporters.
DRUG RESISTANCE UPDATES
(2023)
Article
Biochemistry & Molecular Biology
Yan-Qing Li, Megumi Murakami, Yang-Hui Huang, Tai-Ho Hung, Shun-Ping Wang, Yu-Shan Wu, Suresh V. Ambudkar, Chung-Pu Wu
Summary: This study demonstrates that hydroxygenkwanin can reverse multidrug resistance in cancer cells by inhibiting the drug transport function of ABCG2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Hongtao Zhao
Summary: Kinetic modeling provides insights into the relationship between substrate-Pgp interactions and efflux. Matched molecular pair analysis supports guidelines for efflux control, but rule-based approaches may be insufficient. PROTACs show a preference for physicochemical properties opposite to rule-of-five compliant compounds. Passive permeability plays a critical role in efflux ratio and its mitigation often involves increasing passive permeability.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Iris L. K. Wong, Xuezhen Zhu, Kin-Fai Chan, Zhen Liu, Chin-Fung Chan, Tsun Sing Chow, Tsz Cheung Chong, Man Chun Law, Jiahua Cui, Larry M. C. Chow, Tak Hang Chan
Summary: The synthesized triazole-containing flavonoids exhibit potent and selective BCRP inhibitory activity in cells overexpressing BCRP, showing promise for combination therapy to overcome multidrug resistance in cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Tomoka Gose, Heather M. Aitken, Yao Wang, John Lynch, Evadnie Rampersaud, Yu Fukuda, Medb Wills, Stefanie A. Baril, Robert C. Ford, Anang Shelat, Megan L. O' Mara, John D. Schuetz
Summary: This research reveals the mechanism of substrate selection by ABCG2, identifying a crucial residue N436 that acts as a discriminator for substrate recognition and is required for optimal inhibitor action.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Nikola Pastvova, Petr Dolezel, Petr Mlejnek
Summary: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults with complex genetic alterations and protection from the blood-brain barrier (BBB). The study found that heat shock protein 90 (HSP90) inhibitors, GDN and 17-AAG, induced extensive cell death with apoptotic characteristics in glioma cell lines, regardless of genetic alterations. These inhibitors were weak substrates of ABCB1 and ABCG2, suggesting potential benefits for GBM patients.
Article
Chemistry, Multidisciplinary
Stephanie A. Newman, Jennifer L. Short, Joseph A. Nicolazzo
Summary: This study investigates the impact of ferric ammonium citrate (FAC) on the expression of BCRP and reveals that FAC downregulates ABCG2 mRNA through ROS and ERK1/2 signaling pathways. These mechanisms could be exploited to modulate the expression of BCRP at the BBB.
PHARMACEUTICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Rossitza N. Irobalieva, Ioannis Manolaridis, Scott M. Jackson, Dongchun Ni, Els Pardon, Henning Stahlberg, Jan Steyaert, Kaspar P. Locher
Summary: This study explores the potential of inhibitors targeting sites other than the substrate binding pocket of ABCG2 and develops novel nanobodies as inhibitors. The results show that these nanobodies allosterically bind to different regions of the nucleotide binding domains and prevent the transporter from undergoing conformational changes required for substrate transport.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chung-Pu Wu, Yen-Ching Li, Megumi Murakami, Sung-Han Hsiao, Yun-Chieh Lee, Yang-Hui Huang, Yu-Tzu Chang, Tai-Ho Hung, Yu-Shan Wu, Suresh V. Ambudkar
Summary: This study aims to evaluate whether furmonertinib overcomes drug resistance mediated by ABCB1 and ABCG2 transporters, and explore its interaction mechanisms with these proteins. The results suggest that furmonertinib holds potential as a candidate for combination therapy, enhancing the efficacy of conventional anticancer drugs and overcoming MDR in cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Benjamin Fredrick Gruenbaum, Alexander Zlotnik, Amit Frenkel, Ilya Fleidervish, Matthew Boyko
Summary: Depression is a leading cause of disability globally, yet conventional antidepressant therapies often prove ineffective. Recent studies have identified promising glutamate-based approaches as alternatives to traditional treatments. This review explores the involvement of the glutamate system in depression and offers new insights into therapeutic strategies, particularly in relation to blood-brain barrier permeability. The authors propose further investigation into the use of blood glutamate scavengers for conditions associated with impaired blood-brain barrier function, including depression following stroke or traumatic brain injury, and neurodegenerative diseases.
Article
Veterinary Sciences
Luisa De Risio, Sofie Bhatti, Karen Munana, Jacques Penderis, Veronika Stein, Andrea Tipold, Mette Berendt, Robyn Farqhuar, Andrea Fischer, Sam Long, Paul J. J. Mandigers, Kaspar Matiasek, Rowena M. A. Packer, Akos Pakozdy, Ned Patterson, Simon Platt, Michael Podell, Heidrun Potschka, Marti Pumarola Batlle, Clare Rusbridge, Holger A. Volk
BMC VETERINARY RESEARCH
(2015)
Article
Immunology
Andreas Walker, Vera Russmann, Cornelia A. Deeg, Christine von Toerne, Kristina J. H. Kleinwort, Christoph Szober, Maruja L. Rettenbeck, Eva-Lotta von Rueden, Joanna Goc, Tanja Ongerth, Katharina Boes, Josephine D. Salvamoser, Annamaria Vezzani, Stefanie M. Hauck, Heidrun Potschka
BRAIN BEHAVIOR AND IMMUNITY
(2016)
Article
Clinical Neurology
Vera Russmann, Josephine D. Salvamoser, Maruja L. Rettenbeck, Takafumi Komori, Heidrun Potschka
Article
Pharmacology & Pharmacy
Vera Russmann, Joanna Goc, Katharina Boes, Tanja Ongerth, Josephine D. Salvamoser, Claudia Siegl, Heidrun Potschka
EUROPEAN JOURNAL OF PHARMACOLOGY
(2016)
Article
Toxicology
Kathrin Backes, Helga Lorenz, Loic Laplanche, Thomas J. Hudzik, Heidrun Potschka, Katja Hempel
TOXICOLOGY LETTERS
(2016)
Review
Biochemistry & Molecular Biology
Alexander G. Zestos, Hiram Luna-Munguia, William C. Stacey, Robert T. Kennedy
ACS CHEMICAL NEUROSCIENCE
(2019)
Article
Multidisciplinary Sciences
Hiram Luna-Munguia, Philip Starski, Wu Chen, Stephen Gliske, William C. Stacey
SCIENTIFIC REPORTS
(2017)
Correction
Multidisciplinary Sciences
Hiram Luna-Munguia, Phillip Starski, Wu Chen, Stephen Gliske, William C. Stacey
SCIENTIFIC REPORTS
(2017)
Article
Neurosciences
Hiram Luna-Munguia, Alexander G. Zestos, Stephen V. Gliske, Robert T. Kennedy, William C. Stacey
NEUROBIOLOGY OF DISEASE
(2019)
Article
Behavioral Sciences
Hiram Luna-Munguia, Deisy Gasca-Martinez, Luis Marquez-Bravo, Luis Concha
BRAIN AND BEHAVIOR
(2020)
Article
Clinical Neurology
Hiram Luna-Munguia, Luis Marquez-Bravo, Luis Concha
Summary: This study examined temporal tissue changes following experimental status epilepticus in an animal model of chronic temporal lobe epilepsy. The findings showed early reduction in dorsal hippocampus and fimbria volume in epileptic animals, as well as progressive changes in DTI parameters in both white and gray matter structures. These alterations may serve as potential imaging markers for epileptogenesis.
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY
(2021)
Article
Agriculture, Dairy & Animal Science
Lukas Breuer, Lucas Moesch, Janosch Kunczik, Verena Buchecker, Heidrun Potschka, Michael Czaplik, Carina Barbosa Pereira
Summary: By analyzing visible breathing movement in the thorax, researchers used camera-based methods to monitor the respiratory rate of laboratory rats. This study contributes to the development of non-invasive monitoring methods for rodents, reducing the need for implanted sensors and minimizing stress and pain for the animals.
Article
Agriculture, Dairy & Animal Science
Larissa Weiss, Anna M. Saller, Julia Werner, Stephanie C. Suess, Judith Reiser, Sandra Kollmansperger, Malte Anders, Heidrun Potschka, Thomas Fenzl, Benjamin Schusser, Christine Baumgartner
Summary: This research aimed to determine when chickens acquire the ability to sense pain during embryonic development. By applying mechanical stimuli to chicken embryos and measuring changes in blood pressure and heart rate, it was found that embryos at around two days before hatching showed significant responses to noxious stimuli, indicating the emergence of nociception.
Review
Biochemistry & Molecular Biology
Cecilia Zavala-Tecuapetla, Manola Cuellar-Herrera, Hiram Luna-Munguia
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)