Results 21 to 30 of about 111,693 (253)

Development of a Fast and Sensitive UPLC–MS/MS Analytical Methodology for Fenebrutinib Estimation in Human Liver Microsomes: In Vitro and In Silico Metabolic Stability Evaluation

Separations, 2023
Fenebrutinib (GDC-0853; FNB) is an oral small molecule that was developed by Roche Pharmaceuticals to slow multiple sclerosis progression. FNB is a reversible bruton tyrosine kinase (BTK) inhibitor, which showed the maximum potency of BTK inhibitors in ...
Mohamed W. Attwa, Aishah M. Alsibaee, Haya I. Aljohar, Ali S. Abdelhameed, Adnan A. Kadi   +4 more
doaj   +1 more source

Intrinsic Clearance Assay Incubational Binding: A Method Comparison [PDF]

Drug Metabolism and Disposition, 2017
The fraction of unbound drug (fuinc) in in vitro intrinsic clearance (CLint) incubation is an important parameter in the pursuit of accurate clearance predictions and is often predicted using algorithms based on drug lipophilicity measures. However, analysis of an AstraZeneca database suggests that simple lipophilicity alone is a relatively poor ...
Sofia, Chen, Luna, Prieto Garcia, Fredrik, Bergström, Pär, Nordell, Ken, Grime   +4 more
openaire   +2 more sources

A highly sensitive LC-MS/MS method to determine novel Bruton's tyrosine kinase inhibitor spebrutinib: application to metabolic stability evaluation [PDF]

Royal Society Open Science, 2019
Spebrutinib (SBT) is a Bruton's tyrosine kinase inhibitor. SBT is currently in phase II and phase I clinical trials for the management of rheumatoid arthritis and chronic lymphocytic leukaemia, respectively.
Ali S. Abdelhameed, Mohamed W. Attwa, Nasser S. Al-Shaklia, Adnan A. Kadi   +3 more
doaj   +1 more source

The Specific Mechanism of TREM2 Regulation of Synaptic Clearance in Alzheimer’s Disease

Frontiers in Immunology, 2022
Alzheimer’s disease (AD) is a progressive neurodegenerative disease. Synaptic dysfunction is an integral feature of AD pathophysiology and a significant factor in early cognitive impairment in AD.
Qi Qin, Qi Qin, Meng Wang, Yunsi Yin, Yi Tang, Yi Tang   +5 more
doaj   +1 more source

Using partition analysis as a facile method to derive net clearances

Clinical and Translational Science, 2022
Partition analysis has been described previously by W.W. Cleland to derive net rate constants and simplify the derivation of enzyme kinetic equations. Here, we show that partition analysis can be used to derive elimination and transfer (distribution) net
Ken Korzekwa, Jaydeep Yadav, Swati Nagar
doaj   +1 more source

QSARs for estimating intrinsic hepatic clearance of organic chemicals in humans

Environmental Toxicology and Pharmacology, 2016
Quantitative structure-activity relationships (QSARs) were developed to predict the in vitro clearance (CLINT) of xenobiotics metabolised in human hepatocytes (118 compounds) and microsomes (115 compounds). Clearance values were gathered from the scientific literature and multiple linear models were built and validated selecting at most 6 predictors ...
Pirovano, Alessandra, Brandmaier, Stefan, Huijbregts, Mark A.J., Ragas, A.M.J., Veltman, Karin, Hendriks, A. Jan   +5 more
openaire   +4 more sources

Prediction of Metabolite‐to‐Parent Drug Exposure: Derivation and Application of a Mechanistic Static Model

Clinical and Translational Science, 2020
In the development of new drugs, the prediction of metabolite‐to‐parent plasma exposure ratio in humans prior to administration in a clinical study has emerged as an important need.
Ernesto Callegari, Manthena V.S. Varma, R. Scott Obach   +2 more
doaj   +1 more source

Simplifying the Execution of HepatoPac MetID Experiments: Metabolite Profile and Intrinsic Clearance Comparisons [PDF]

Drug Metabolism and Disposition, 2020
The HepatoPac micropatterned coculture (MPCC) hepatocyte system has been shown to be an effective tool to investigate the qualitative human and preclinical species' metabolite profiles of new drug candidates. However, additional improvements to the overall study conditions and execution, layout, and human-donor count could be made. To that end, we have
T Eric, Ballard, N, Kratochwil, Loretta M, Cox, Mark A, Moen, F, Klammers, A, Ekiciler, A, Goetschi, I, Walter   +7 more
openaire   +2 more sources

Metabolic stability and its role in the discovery of new chemical entities

Acta Pharmaceutica, 2019
Determination of metabolic profiles of new chemical entities is a key step in the process of drug discovery, since it influences pharmacokinetic characteristics of therapeutic compounds.
Słoczyńska Karolina, Gunia-Krzyżak Agnieszka, Koczurkiewicz Paulina, Wójcik-Pszczoła Katarzyna, Żelaszczyk Dorota, Popiół Justyna, Pękala Elżbieta   +6 more
doaj   +1 more source

The effect of gene polymorphism on ticagrelor metabolism: an in vitro study of 22 CYP3A4 variants in Chinese Han population [PDF]

PeerJ
Background Ticagrelor is a novel oral antiplatelet agent which can selectively inhibit P2Y12 receptor. Bleeding and dyspnea are common adverse reactions of ticagrelor in clinic.
Xiaoxia Hu, Peng Wang, Dali Zeng, Guo-xin Hu   +3 more
doaj   +2 more sources