Article
Oncology
Federica Loscocco, Giuseppe Visani, Annamaria Ruzzo, Irene Bagaloni, Fabio Fuligni, Sara Galimberti, Antonello Di Paolo, Fabio Stagno, Patrizia Pregno, Mario Annunziata, Antonella Gozzini, Sara Barulli, Elisa Gabucci, Mauro Magnani, Alessandro Isidori
Summary: This study identified associations between specific ABCC2 and ABCB1 gene SNPs and achievement of deep molecular responses in CML patients, as well as connections between certain ABC transporter gene SNPs and the maintenance or loss of molecular responses. The study also developed a predictive model incorporating information on four genotypes, which was found to have high prognostic significance for both achieving and maintaining molecular responses.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, Research & Experimental
Charles Awortwe, Henrike Bruckmueller, Meike Kaehler, Ingolf Cascorbi
Summary: The study investigated the effects of Echinacea purpurea compounds on the expression and transport activity of ABCB1 and ABCG2 proteins, showing heterogeneous induction by the compounds but no significant inhibition of transporter activity was found.
MOLECULAR PHARMACEUTICS
(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
Chiara Dalle Fratte, Jerry Polesel, Sara Gagno, Bianca Posocco, Elena De Mattia, Rossana Roncato, Marco Orleni, Fabio Puglisi, Michela Guardascione, Angela Buonadonna, Giuseppe Toffoli, Erika Cecchin
Summary: This study investigated the association between genetic polymorphisms in ABCB1 and ABCG2 and imatinib plasma trough concentration in GIST and CML patients. The results showed a borderline association between the ABCG2 c.421C>A genotype and imatinib plasma trough levels, which was further confirmed in a meta-analysis. However, no significant association was found between ABCB1 polymorphisms and imatinib C-trough.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Hui Li, Sheng-Lie Zhang, Yan-Han Jia, Qian Li, Zi-Wen Feng, Shi-Duo Zhang, Wei Zheng, Ye-Ling Zhou, Lin-Lin Li, Xue-Chun Liu, Ya-Qiong Chen, Hui Peng, Qi-Dong You, Xiao-Li Xu
Summary: ABCB1 and ABCG2 are important ATP-binding cassette (ABC) transporters associated with multidrug resistance (MDR). In this study, we designed a series of imidazo[1,2-a]pyridine derivatives as dual-target inhibitors of ABCB1 and ABCG2 through scaffold hopping strategy. Compound Y22 demonstrated potential efflux function inhibition towards both ABCB1 and ABCG2 without cytotoxicity, and enhanced the potency of antiproliferative drugs in vitro. Mechanistic studies showed that Y22 slightly suppressed ATPase activity, but did not affect the protein expression of ABCB1 or ABCG2. Notably, Y22 exhibited negligible CYP3A4 inhibition and enhanced the antiproliferative activity of adriamycin in vivo by restoring the sensitivity of resistant cells. Thus, Y22 may be effective clinically in combination with common chemotherapy agents.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Myriam El Biali, Rudolf Karch, Cecile Philippe, Helmuth Haslacher, Nicolas Tournier, Marcus Hacker, Markus Zeitlinger, Doreen Schmidl, Oliver Langer, Martin Bauer
Summary: The study suggests that ABCB1 and ABCG2 together limit the distribution of systemically administered ABCB1/ABCG2 substrate drugs to the human retina, with carriers of the c.421C > A SNP possibly being more susceptible to transporter-mediated drug-drug interactions at the blood-retinal barrier.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Changfu Liu, Wenge Xing, Haipeng Yu, Weihao Zhang, Tongguo Si
Summary: The findings suggest that overexpression of ABCB1 and ABCG2 may restrict the efficacy of Gedatolisib in colorectal cancer cells, while co-administration with ABC transporter inhibitors may improve the potency of Gedatolisib.
CANCER CELL INTERNATIONAL
(2021)
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)
Article
Pharmacology & Pharmacy
Youssif Budagaga, Ziba Sabet, Yu Zhang, Eva Novotna, Ivo Hanke, Tomas Rozkos, Jakub Hofman
Summary: Tazemetostat is a unique multispecific chemosensitizer that can inhibit multiple ABC transporters and enhance the synergistic effect of chemotherapy by inducing apoptosis.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Henrike Bruckmueller, Ingolf Cascorbi
Summary: Despite significant efforts, studies on genetic variants in ABC efflux transporters have shown weak associations with drug pharmacokinetics and response. Majority of studies have failed to confirm earlier findings and remain inconsistent. The impact of genetic variants on drug bioavailability is minor, with other factors regulating transporter expression and function being more critical. Overall, these genetic variants are not suitable as predictive biomarkers.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ziba Sabet, Dimitrios Vagiannis, Youssif Budagaga, Yu Zhang, Eva Novotna, Ivo Hanke, Tomas Rozkos, Jakub Hofman
Summary: This study provides a comprehensive overview of the pharmacokinetic drug-drug interactions of talazoparib and introduces it as an efficient multidrug resistance antagonist.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Yu Siong Ho, Pablo Torres-Vergara, Jeffrey Penny
Summary: This study investigated the effects of NR3C1, NR1I3, NR1I2 and NR2B1 activation on porcine brain endothelial cells (PBECs). The results showed that NR1I2 agonist Rifampicin up-regulated ABCG2 activity, while NR1I2 antagonist L-sulforaphane counteracted this effect. NR1I3 agonist and inverse agonist down-regulated ABCB1, ABCG2 and ABCC5 activity. NR3C1 agonist increased ABCB1, ABCG2 and ABCC5 activity and protein expression, which was counteracted by NR3C1 antagonist. NR1I3 and NR3C1 were found to regulate ABCC5 activity and protein expression in BBB endothelial cells.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Chung-Pu Wu, Ya-Ju Hsieh, Han-Yu Tseng, Yang-Hui Huang, Yan-Qing Li, Tai-Ho Hung, Shun-Ping Wang, Yu-Shan Wu
Summary: This study demonstrates that WDR5-0103 can reverse multidrug resistance mediated by ABCB1 and ABCG2. It enhances the sensitivity of multidrug-resistant cancer cells to conventional cytotoxic drugs by inhibiting the drug-efflux function of ABCB1 and ABCG2.
BIOMEDICINE & PHARMACOTHERAPY
(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
Oncology
Miwako Omori, Rintaro Noro, Masahiro Seike, Kuniko Matsuda, Mariko Hirao, Aya Fukuizumi, Natsuki Takano, Akihiko Miyanaga, Akihiko Gemma
Summary: This study identified key factors in the chemoresistance of SCLC, including drug efflux proteins ABCB1 and ABCG2. Inhibiting these proteins can restore drug sensitivity and promote apoptotic activity in SCLC cells. ABC transporter inhibitors may be a promising therapeutic strategy for overcoming resistance to topoisomerase inhibitors in SCLC patients.
Article
Hematology
Tatsiana V. Shman, Uladzimir U. Fedasenka, Valery P. Savitski, Olga V. Aleinikova
ANNALS OF HEMATOLOGY
(2008)
Article
Chemistry, Medicinal
O. V. Stasevich, T. V. Shman, S. G. Mikhalenok, V. P. Kurchenko
CHEMISTRY OF NATURAL COMPOUNDS
(2010)
Letter
Oncology
Tatsiana V. Shman, Ludmila V. Movchan, Olga V. Aleinikova
LEUKEMIA & LYMPHOMA
(2013)
Meeting Abstract
Hematology
N. Lipay, T. Shman
THROMBOSIS RESEARCH
(2010)
Article
Biochemistry & Molecular Biology
A. G. Kadushkin, A. D. Tahanovich, L. V. Movchan, T. S. Kolesnikova, E. V. Khadasouskaya, T. V. Shman
Summary: This study aimed to evaluate the ability of azithromycin and theophylline to enhance the anti-inflammatory effects of glucocorticoids on cytokine production by NK and NKT-like blood cells in COPD patients. The results showed that the combination of azithromycin and budesonide or theophylline and budesonide had a more pronounced inhibitory effect on cytokine production in these cells compared to using glucocorticoids alone, indicating the benefits of combined therapy in suppressing inflammation in COPD patients.
BIOCHEMISTRY MOSCOW-SUPPLEMENT SERIES B-BIOMEDICAL CHEMISTRY
(2021)
Article
Respiratory System
Aliaksei Kadushkin, Anatoli Tahanovich, Lyudmila Movchan, Elina Talabayeva, Alena Plastinina, Tatiana Shman
Summary: This study found that the combination of azithromycin and budesonide can enhance the anti-inflammatory properties of glucocorticoids in blood cells of COPD patients.
ADVANCES IN RESPIRATORY MEDICINE
(2022)
Article
Medicine, Research & Experimental
Tatsiana V. Shman, Katsiaryna P. Vashkevich, Alexandr A. Migas, Mikhail A. Matveyenka, Yauheni A. Lasiukov, Nastassia S. Mukhametshyna, Katsiaryna I. Horbach, Olga V. Aleinikova
Summary: In this study, we characterized the expansion, phenotype, and functional activity of NK cells obtained for a clinical trial. We found that ex vivo expansion of NK cells resulted in a relatively undifferentiated phenotype and enhanced cytolytic activity against cancer cells.
CLINICAL AND EXPERIMENTAL MEDICINE
(2022)
Meeting Abstract
Respiratory System
Anatoli Tahanovich, A. G. Kadushkin, L. V. Movchan, T. V. Shman, V. V. Levandovskaya
EUROPEAN RESPIRATORY JOURNAL
(2018)
Article
Medicine, Research & Experimental
T. V. Shman, V. P. Savitskii, M. P. Potapnev, O. V. Aleinikova
BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE
(2006)
Article
Medical Laboratory Technology
VP Savitskiy, TV Shman, MP Potapnev
CYTOMETRY PART B-CLINICAL CYTOMETRY
(2003)