A5016889491- Drug Transport and Resistance Mechanisms
- Peripheral Neuropathies and Disorders
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Receptor Mechanisms and Signaling
- Pharmacogenetics and Drug Metabolism
- Complement system in diseases
Utrecht University
2022
Abstract With the addition of compstatin-based complement C3 inhibitor pegcetacoplan, another class targeted therapeutics have recently been approved. Moreover, compstatin derivatives with enhanced pharmacodynamic and pharmacokinetic profiles are in clinical development (e.g., Cp40/AMY-101). Despite this progress, target binding inhibitory modes family remain incompletely described. Here, we present crystal structure Cp40 complexed its C3b at 2.0-Å resolution. Structure-activity-relationship...
ABSTRACT Membrane proteins (MPs) are important yet challenging targets for drug discovery. MPs can be reconstituted in protein‐lipid Nanodiscs (NDs), which resemble the native membrane environment. Drug‐membrane interactions affect apparent binding stoichiometry and affinity, as well kinetics of ligands a particular target, is extrapolation to pharmacokinetic studies. To investigate role membrane, we have applied fragment‐based discovery (FBDD) methods cytochrome P450 3A4 (CYP3A4), NDs...