Publications by authors named "L Berezhkovskiy"
Article Synopsis
- NF-κB-inducing kinase (NIK) plays a key role in the noncanonical NF-κB pathway, affecting processes like B cell maturation and dendritic cell activation.
- Researchers identified a series of potent NIK inhibitors using a scaffold-hopping strategy combined with structure-based design, focusing on optimizing chemical properties.
- One of the top compounds, 4f, demonstrated effective inhibition of B cell survival linked to BAFF in lab tests, and it showed a favorable pharmacokinetic profile across different species in vivo.
Article Synopsis
- NIK is a key mediator in non-canonical NF-κB signaling linked to several TNF family members involved in system lupus erythematosus (SLE) pathology.
- Inhibition of NIK using a selective small molecule shows similar effects to BAFF blockade, successfully improving conditions in experimental lupus models.
- NIK inhibition leads to better survival rates, less kidney damage, and reduced proteinuria, indicating its potential as a new treatment strategy for SLE.
An uncommon innovative consideration of the well-stirred linear physiologically based pharmacokinetic model and the drug plasma concentration-time profile, which is measured in routine intravenous bolus pharmacokinetic study, was applied for the calculation of the drug time course in human tissues. This cannot be obtained in the in vivo pharmacokinetic study. The physiological parameters of the organ such as organ tissue volume, organ blood flow rate, and its vascular volume were used in the calculation.
View Article and Find Full Text PDF1. The steady state and terminal volumes of distribution, as well as the mean residence time of drug in the body (Vss, Vβ, and MRT) are the common pharmacokinetic parameters calculated using the drug plasma concentration-time profile (Cp(t)) following intravenous (iv bolus or constant rate infusion) drug administration. 2.
View Article and Find Full Text PDFBackground: The use of liver microsomes and hepatocytes to predict total in vivo clearance is standard practice in the pharmaceutical industry; however, metabolic stability data alone cannot always predict in vivo clearance accurately.
Results: Apparent permeability generated from Mardin-Darby canine kidney cells and rat hepatocyte uptake for 33 discovery compounds were obtained.
Conclusion: When there is underprediction of in vivo clearance, compounds with low apparent permeability (less than 3 × 10(-6) cm/s) all exhibited hepatic uptake.