Article
Chemistry, Medicinal
Md Khalilur Rahman, Yassir Al-Zubaidi, Kirsi Bourget, Yongjuan Chen, Stanton Tam, Fanfan Zhou, Michael Murray
Summary: Long-term use of cytotoxic agents promotes drug resistance in triple-negative breast cancer. Combination analysis showed that the combination of ixabepilone with VEGFR inhibitors and PARP inhibitors effectively reduced cell viability, suggesting potential clinical applications.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Lara Garcia-Varela, Pascalle Mossel, Pablo Aguiar, Daniel A. Vazquez-Matias, Aren van Waarde, Antoon T. M. Willemsen, Anna L. Bartels, Nicola A. Colabufo, Rudi A. J. O. Dierckx, Philip H. Elsinga, Gert Luurtsema
Summary: This study found that small changes in P-gp function caused by low doses of tariquidar could be detected by [F-18]MC225-K-1 values, confirming the high sensitivity of the radiotracer.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Biochemistry & Molecular Biology
Qingjie Xiao, Ting Xue, Wen Shuai, Chengyong Wu, Zhixiong Zhang, Ting Zhang, Shaoxue Zeng, Bo Sun, Yuxi Wang
Summary: Crystal structures of three taxane-site inhibitors, Ixabepilone, Epothilone B, and Epothilone D, were reported, showing similar binding modes to promote tubulin polymerization. Through virtual screening, novel taxane-site inhibitors with simpler chemical structures were identified, and derivatives with higher binding affinity to tubulin were designed and developed.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Sarah Lazzaro, Mark A. West, Soraya Eatemadpour, Bo Feng, Manthena V. S. Varma, A. David Rodrigues, Csilla Temesszentandrasi-Ambrus, Peter Kovacs-Hajdu, Zsuzsanna Nerada, Zsuzsanna Gaborik, Chester Costales
Summary: This study evaluated the impact of potential IC50 discrepancies between two commonly utilized assay methods (cell-based and vesicle-based) on P-gp. Non-P-gp substrates showed good correlation between the two methods, while IC50s of P-gp substrates were lower in the vesicle assays. IC50s obtained from two independent laboratories using the same method showed good correlation.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Review
Oncology
Nuhad K. Ibrahim
Summary: The epothilone drug class, including ixabepilone, has shown efficacy and safety in the treatment of metastatic breast cancer, demonstrating improved progression-free survival and overall response rates in patients who have progressed during chemotherapy. Additionally, ixabepilone's clinical benefit in special populations has been characterized, with evidence supporting its use in specific patient groups such as those with triple-negative breast cancer. Dose reductions do not appear to impact the efficacy of ixabepilone, making it a valuable option for individualized treatment plans in patients with unmet needs.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Dana M. Roque, Eric R. Siegel, Natalia Buza, Stefania Bellone, Dan-Arin Silasi, Gloria S. Huang, Vaagn Andikyan, Mitchell Clark, Masoud Azodi, Peter E. Schwartz, Gautam G. Rao, Jocelyn C. Reader, Pei Hui, Joan R. Tymon-Rosario, Justin Harold, Dennis Mauricio, Burak Zeybek, Gulden Menderes, Gary Altwerger, Elena Ratner, Alessandro D. Santin
Summary: This multi-center study evaluated the activity and safety of ixabepilone plus bevacizumab compared to ixabepilone alone in platinum-resistant/refractory ovarian cancer. The results showed that the combination of ixabepilone and bevacizumab had a higher overall response rate and longer progression-free survival, with good tolerability. Prior receipt of bevacizumab should not limit the use of ixabepilone plus bevacizumab in treatment.
BRITISH JOURNAL OF CANCER
(2022)
Article
Pharmacology & Pharmacy
Leandro Francisco Pippa, Carolina Pinto Vieira, Juciene Aparecida Caris, Adriana Rocha, Maria Paula Marques, Camile Prates Garcia, Rosamar Eulira Fontes Rezende, Vera Lucia Lanchote
Summary: This study evaluated the activity of OATP1B1, BCRP, and P-gp in patients with chronic HCV infection before and after treatment with direct-acting antiviral agents. The activity of these transporters was found to be reduced in patients with different levels of liver fibrosis, both before and after treatment. Clinicians should take into consideration the treatment response and stage of HCV infection when administering substrates of these transporters with low therapeutic indexes.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Lea Darnaud, Clement Delage, Youssef Daali, Anne-Priscille Trouvin, Serge Perrot, Nihel Khoudour, Nadia Merise, Laurence Labat, Bruno Etain, Frank Bellivier, Celia Lloret-Linares, Vanessa Bloch, Emmanuel Curis, Xavier Decleves
Summary: Drug-metabolizing enzymes and drug transporters play crucial roles in drug pharmacokinetics and response. The cocktail-based phenotyping approach involves administering multiple probe drugs to evaluate the activities of CYP and transporter simultaneously. This study determined the range of phenotyping indices in healthy volunteers and classified patients with therapeutic issues based on CYP and P-gp activities.
Article
Hematology
Floris Bosch, Frits Mulder, Linda Franken, Annelieke Willemsen, Marjolein Rentinck, Pieter van den Berg, Sylvia Luykx-de Bakker, Ankie van der Velden, Nick van Es, Ron Matho, Pieter W. Kamphuisen
Summary: This study aimed to assess the effect of tamoxifen, a commonly used P-glycoprotein inhibitor, on edoxaban clearance. The results showed that simultaneous use of tamoxifen and edoxaban did not result in reduced clearance of edoxaban in breast cancer patients.
THROMBOSIS RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Austin Sun, Joanne Wang
Summary: This study investigates the functional activity of P-gp and Bcrp at the murine blood-cerebrospinal fluid barrier (BCSFB) using live tissue imaging. The results show that Bcrp has functional activity at the apical membrane of the BCSFB, and P-gp may also have additional contributions.
PHARMACEUTICAL RESEARCH
(2023)
Article
Cell Biology
Yuling Chen, Xiaohong Li, Lei Shi, Pengfei Ma, Wei Wang, Nan Wu, Youlin Gan, Xu Han, Shanshan Huang, Xiaohui Kang, Shuxin Liu, Yuhong Zhen
Summary: The study demonstrated that the combination of GQ and miR-451 could reverse drug resistance in breast cancer cells by reducing the expression of MDR1 and P-gp.
Article
Pharmacology & Pharmacy
Stanton Tam, Yassir Al-Zubaidi, Md Khalilur Rahman, Kirsi Bourget, Fanfan Zhou, Michael Murray
Summary: This study evaluated the efficacy of clinically approved EGFR inhibitors in combination with the cytotoxic agent ixabepilone in TNBC cells. The combination of ixabepilone and vandetanib showed synergistic effects on cell proliferation and apoptosis, while the combination of ixabepilone and gefitinib exhibited antagonism.
PHARMACOLOGICAL REPORTS
(2022)
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
Pharmacology & Pharmacy
Louise Breuil, Sebastien Goutal, Solene Marie, Antonio Del Vecchio, Davide Audisio, Amelie Soyer, Maud Goislard, Wadad Saba, Nicolas Tournier, Fabien Caille
Summary: This study compared the efflux and brain exposure of domperidone and metoclopramide at the blood-brain barrier using PET imaging. The results showed that domperidone had lower penetration and exposure in the brain compared to metoclopramide.
Article
Pharmacology & Pharmacy
Sho Shimazaki, Junko Kuroda, Kenju Shimomura, Shingen Misaka
Summary: The study suggests that measuring the urinary excretion of nadolol can be a sensitive and reliable alternative to plasma pharmacokinetics for the evaluation of P-glycoprotein-mediated drug interactions.
JOURNAL OF CLINICAL PHARMACOLOGY
(2021)