Article
Medicine, Research & Experimental
Maria Lucia Souza Siqueira, Sara Michelli Vieira Andrade, Jose Luiz Fernandes Vieira, Marta Chagas Monteiro
Summary: The long-term use of tamoxifen in breast cancer patients can affect lipid metabolism, but the relationship between blood lipids and the plasma concentrations of tamoxifen and its active metabolites is not significant. Weak associations were found between the plasma concentrations of tamoxifen and the active metabolites with HDL-c, LDL-c, and VLDL-c.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Medicine, Research & Experimental
Yung-Yi Cheng, Elise T. Tuzo, Jeffrey W. Dalley, Tung-Hu Tsai
Summary: The study revealed that pre-treatment with Hedyotis diffusa extract led to a decrease in the bioavailability of tamoxifen and affected its clinical efficacy. High doses of Hedyotis diffusa extract also influenced the conversion ratios of tamoxifen metabolites.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Alejandra Martinez-Chavez, Nancy H. C. Loos, Maria C. Lebre, Matthijs M. Tibben, Hilde Rosing, Jos H. Beijnen, Alfred H. Schinkel
Summary: The study reveals that both ABCB1 and ABCG2 proteins profoundly limit the brain penetration of abemaciclib and its active metabolites, and are likely involved in their elimination through the liver, bile, or intestines. Additionally, the human CYP3A4 gene significantly reduces the plasma concentration of abemaciclib, highlighting its importance in the clinical development of abemaciclib for brain malignancies.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Medicine, Research & Experimental
Margarida L. F. Martins, Nancy H. C. Loos, Sumeyra Mucuk, Danielle de Jong, Maria C. Lebre, Hilde Rosing, Matthijs Tibben, Jos H. Beijnen, Alfred H. Schinkel
Summary: The study found that Abcb1 deficiency significantly increased the distribution of niraparib in the brain and reduced its recovery in the small intestine, which was completely inhibited by Elacridar pretreatment. OATP1 and CYP3A had minimal impact on the metabolism and distribution of niraparib, which could be advantageous in reducing the risk of drug-drug interactions or interindividual variation.
MOLECULAR PHARMACEUTICS
(2021)
Article
Chemistry, Multidisciplinary
Margarida L. F. Martins, Nancy H. C. Loos, Malika el Yattouti, Lianda Offeringa, Paniz Heydari, Michel J. X. Hillebrand, Maria C. Lebre, Jos H. Beijnen, Alfred H. Schinkel
Summary: The study found that mAbcb1a/1b can limit the exposure of 6-MAM and morphine in the brain. Genetic polymorphisms or environmental factors (such as drug interactions) may have a limited effect on the exposure of 6-MAM and morphine in individuals.
PHARMACEUTICAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Margarida L. F. Martins, Paniz Heydari, Wenlong Li, Alejandra Martinez-Chavez, Nikkie Venekamp, Maria C. Lebre, Luc Lucas, Jos H. Beijnen, Alfred H. Schinkel
Summary: This study investigated the impact of drug transporters and drug-metabolizing complex on the pharmacokinetics of ibogaine and its metabolites. The results showed that drug efflux and uptake transporters have a modest restricting effect on the systemic exposure and brain penetration of ibogaine, while drug-metabolizing complex had negligible impact on ibogaine pharmacokinetics.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Kuljeet Singh, Szabolcs Tarapcsak, Zsuzsanna Gyoengy, Zsuzsanna Ritter, Gyula Batta, Rosevalentine Bosire, Judit Remenyik, Katalin Goda
Summary: P-glycoprotein (Pgp) is an important transporter protein involved in drug absorption, metabolism, and excretion, and its overexpression in cancer cells leads to drug resistance. Some polyphenols from sour cherry origin have been shown to inhibit Pgp activity and increase drug accumulation in positive cells, while others increase Pgp activity with weaker effects on drug accumulation. These polyphenols can potentially interact with Pgp and influence drug resistance in cancer cells.
Article
Pharmacology & Pharmacy
Alejandra Martinez-Chavez, Jelle Broeders, Maria C. Lebre, Matthijs T. Tibben, Hilde Rosing, Jos H. Beijnen, Alfred H. Schinkel
Summary: The pharmacokinetics of the promising anticancer drug milciclib is influenced by various transporters and drug-metabolizing enzymes, with ABCB1 and ABCG2 cooperatively limiting its brain penetration.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Wenlong Li, Daniela Lehutova, Rolf W. Sparidans, Paniz Heydari, Jing Wang, Maria C. Lebre, Jos H. Beijnen, Alfred H. Schinkel
Summary: In this study, the functions of ABC transporters (ABCB1 and ABCG2), uptake transporters (OATP1A/1B), and drug-metabolizing enzyme complex (CYP3A) in the pharmacokinetics of Cintirorgon were investigated. The results showed that ABCB1 and Oatp1a/1b played important roles in the brain penetration and systemic exposure of Cintirorgon, while CYP3A affected its oral availability.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2022)
Article
Chemistry, Medicinal
Yaogeng Wang, Rolf W. Sparidans, Sander Potters, Rahime Senturk, Maria C. Lebre, Jos H. Beijnen, Alfred H. Schinkel
Summary: The study showed that ABCG2, especially ABCB1, limit the brain and testis penetration of selpercatinib, while CYP3A-mediated metabolism may affect selpercatinib's oral exposure and tissue concentrations.
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)
Review
Biochemistry & Molecular Biology
Liadys Mora Lagares, Marjana Novic
Summary: ABC transporters, especially P-glycoprotein (P-gp), play a critical role in drug bioavailability and toxicity. Efforts to reverse multidrug resistance (MDR) associated with overexpression of P-gp have been extensive but have yet to yield effective inhibitors due to their toxic effects. Computational studies and in silico models have shown promise in accelerating the development of P-gp inhibitors and understanding drug-transporter interactions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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)
Review
Pharmacology & Pharmacy
Jinyun Dong, Li Yuan, Can Hu, Xiangdong Cheng, Jiang -Jiang Qin
Summary: Multidrug resistance (MDR) is a major threat in chemotherapy, and the overexpression of ATP-binding cassette (ABC) transporters, particularly P-glycoprotein (P-gp)/ABCB1, plays a role in MDR. Targeting P-gp with small molecule inhibitors is an effective approach, but no clinically useful inhibitors have been identified so far. Therefore, further research is needed to overcome MDR.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Alessandro Barbieri, Nopnithi Thonghin, Talha Shafi, Stephen M. Prince, Richard F. Collins, Robert C. Ford
Summary: The study found that the presence of ivacaftor results in an additional density in the central aqueous cavity of P-glycoprotein, which is associated with a wider separation of the transporter's two halves in the inward-facing state. Additionally, conformational changes to the nucleotide-binding domains may help to explain the stimulation of ATPase activity observed when transported substrate is bound in many ATP binding cassette transporters.