Tocchetti, Guillermo Nicolás Domínguez, Camila Juliana Zecchinati, Felipe Arana, Maite Rocío Ruiz, María Laura Villanueva, Silvina Stella Maris Weiss, Johanna Mottino, Aldo Domingo Rigalli, Juan Pablo
Published in
Biochemical pharmacology
ABC transporters are key players in drug excretion with alterations in their expression and activity by therapeutic agents potentially leading to drug-drug interactions. The interaction potential of nomegestrol acetate (NMGA), a synthetic progestogen increasingly used as oral contraceptive, had never been explored. In this work we evaluated (1) the...
Mantuano, Paola Sanarica, Francesca Conte, Elena Morgese, Maria Grazia Capogrosso, Roberta Francesca Cozzoli, Anna Fonzino, Adriano Quaranta, Angelo Rolland, Jean-Francois De Bellis, Michela
...
Published in
Biochemical pharmacology
The pharmacological stimulation of AMP-activated protein kinase (AMPK) via metabolic enhancers has been proposed as potential therapeutic strategy for Duchenne muscular dystrophy (DMD). Metformin, a widely-prescribed anti-hyperglycemic drug which activates AMPK via mitochondrial respiratory chain, has been recently tested in DMD patients in synergy...
St-Pierre, David Cabana, Jérôme Holleran, Brian J Besserer-Offroy, Élie Escher, Emanuel Guillemette, Gaétan Lavigne, Pierre Leduc, Richard
Published in
Biochemical pharmacology
G protein coupled receptors (GPCRs) produce pleiotropic effects by their capacity to engage numerous signaling pathways once activated. Functional selectivity (also called biased signaling), where specific compounds can bring GPCRs to adopt conformations that enable selective receptor coupling to distinct signaling pathways, continues to be signifi...
Harrison, Lauren E Bleiler, Marina Giardina, Charles
Published in
Biochemical pharmacology
Cancer cells have long been noted for alterations in centrosome structure, number, and function. Colorectal cancers are interesting in this regard since two frequently mutated genes, APC and CTNNB1 (β-catenin), encode proteins that directly interact with the centrosome and affect its ability to direct microtubule growth and establish cell polarity....
Granja-Galeano, Gina Zappia, Carlos Daniel Fabián, Lucas Davio, Carlos Shayo, Carina Fernández, Natalia Monczor, Federico
Published in
Biochemical pharmacology
Despite the pivotal role GPCRs play in cellular signaling, it is only in the recent years that structural biology has begun to elucidate how GPCRs function and to provide a platform for structure-based drug design. It is postulated that GPCR activation involves the movement of transmembrane helices. The finding that many residues, which have been s...
Papageorgiou, Ioannis Court, Michael H
Published in
Biochemical pharmacology
Posttranscriptional repression of UDP-glucuronosyltransferase (UGT) 2B7 and 2B15 expression by microRNAs (miRNAs) may be an important mechanism underlying inter-individual variability in drug glucuronidation. Furthermore, the UGT2B15 3'-UTR contains a common SNP (rs3100) that could influence miRNA binding. The aim of this study was to identify the ...
Karkhanis, Aneesh Tram, Nhan Dai Thien Chan, Eric Chun Yong
Published in
Biochemical pharmacology
Cardiac enzymes such as cytochrome P450 2J2 (CYP2J2) metabolize arachidonic acid (AA) to cardioprotective epoxyeicosatrienoic acids (EETs), which in turn are metabolized by soluble epoxide hydrolase (sEH) to dihydroxyeicosatrienoic acids (DHETs). As EETs and less potent DHETs exhibit cardioprotective and vasoprotective functions, optimum levels of ...
Yan, Qi Machalz, David Zöllner, Andy Sorensen, Erik J Wolber, Gerhard Bureik, Matthias
Published in
Biochemical pharmacology
We have established a protocol for the preparation of permeabilized fission yeast cells (enzyme bags) that recombinantly express human cytochrome P450 enzymes (CYPs). A direct comparison of CYP3A4 activity gave an eightfold higher space-time yield for enzyme bag-catalyzed biotransformation as compared to whole-cell biotransformation, even though th...
Cheshmehkani, Ameneh Senatorov, Ilya S Dhuguru, Jyothi Ghoneim, Ola Moniri, Nader H
Published in
Biochemical pharmacology
Agonism of the G protein-coupled free-fatty acid receptor-4 (FFA4) has been shown to promote numerous anti-inflammatory effects in macrophages that arise due to interaction with β-arrestin partner proteins. Humans express functionally distinct short and long FFA4 splice variants, such that FFA4-S signals through Gαq/11 and β-arrestin, while FFA4-L ...
Radenkovic, Filip Holland, Olivia Vanderlelie, Jessica J Perkins, Anthony V
Published in
Biochemical pharmacology
Auranofin is a thiol-reactive gold (I)-containing compound with potential asa chemotherapeutic. Auranofin has the capacity to selectively inhibit endogenous antioxidant enzymes thioredoxin reductase (TrxR) and glutathione peroxidase (GPx), resulting in oxidative stress and the initiation of a pro-apoptotic cascade. The effect of Auranofin exposure ...
