Publicaties
Gekozen filters:
Gekozen filters:
Allosteric modulation of a tyrosine kinase receptor by an extracellularly acting small-molecule chemical compound: inhibition of (lymph)angiogenesis in fish,frogs and mice by a multi-FGFR inhibitor KU Leuven
De Receptor Tyrosine Kinase (RTK) superfamilie vormt een uiterst belangrijk doelwit in de huidige ontwikkeling van anti-angiogene/kanker geneesmiddelen. De huidige RTK inhibitoren binden aan en blokkeren de orthostere bindingsplaatsen van de endogene liganden of substraten van hun respectieve receptoren of enzymes. Allostere geneesmiddelen (of middelen die binden aan topografisch verschillende locaties) vormen een groep van veelbelovende ...
BACE1 Dynamics Upon Inhibition with a BACE Inhibitor and Correlation to Downstream Alzheimer's Disease Markers in Elderly Healthy Participants Vlaams Instituut voor Biotechnologie Universiteit Antwerpen KU Leuven Vrije Universiteit Brussel
The PFKFB3 inhibitor AZ67 inhibits angiogenesis independently of glycolysis inhibition Universiteit Antwerpen
Angiogenesis is the process of new blood vessel formation. In this complex orchestrated growth, many factors are included. Lately, focus has shifted to endothelial cell metabolism, particularly to the PFKFB3 protein, a key regulatory enzyme of the glycolytic pathway. A variety of inhibitors of this important target have been studied, and a plethora of biological effects related to the process of angiogenesis have been reported. However, recent ...
Inhibition of Thrombin-Activatable Fibrinolysis Inhibitor and Plasminogen Activator Inhibitor-1 Reduces Ischemic Brain Damage in Mice KU Leuven
BACKGROUND AND PURPOSE: Cerebral ischemia and reperfusion is associated with activation of the coagulation cascade and fibrin deposition in cerebral microvessels. Both thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 (PAI-1) attenuate fibrinolysis and are therefore attractive targets for the treatment of ischemic stroke. METHODS: TAFI and PAI-1 were inhibited by monoclonal antibodies in a mouse model of ...
The Myosin II ATPase Inhibitor Blebbistatin Prevents Thrombin-Induced Inhibition of Intercellular Calcium Wave Propagation in Corneal Endothelial Cells KU Leuven
PURPOSE: Thrombin inhibits intercellular Ca(2+) wave propagation in bovine corneal endothelial cells (BCECs) through a mechanism dependent on myosin light chain (MLC) phosphorylation. In this study, blebbistatin, a selective myosin II ATPase inhibitor, was used to investigate whether the effect of thrombin is mediated by enhanced actomyosin contractility. METHODS: BCECs were exposed to thrombin (2 U/mL) for 5 minutes. MLC phosphorylation was ...
Structural and mechanistic insights into the inhibition of respiratory syncytial virus polymerase by a non-nucleoside inhibitor Universiteit Antwerpen
The respiratory syncytial virus polymerase complex, consisting of the polymerase (L) and phosphoprotein (P), catalyzes nucleotide polymerization, cap addition, and cap methylation via the RNA dependent RNA polymerase, capping, and Methyltransferase domains on L. Several nucleoside and non-nucleoside inhibitors have been reported to inhibit this polymerase complex, but the structural details of the exact inhibitor-polymerase interactions have ...
Discovery of a new Mycobacterium tuberculosis thymidylate synthase X inhibitor with a unique inhibition profile KU Leuven
Tuberculosis (TB), mainly caused by Mycobacterium tuberculosis (Mtb), is an infection that is responsible for roughly 1.5 million deaths per year. The situation is further complicated by the wide-spread resistance to the existing first- and second-line drugs. As a result of this, it is urgent to develop new drugs to combat the resistant bacteria as well as have lower side effects, which can promote adherence to the treatment regimens. Targeting ...
Inhibition of PLK1 Destabilizes EGFR and Sensitizes EGFR-Mutated Lung Cancer Cells to Small Molecule Inhibitor Osimertinib Vrije Universiteit Brussel
Tyrosine kinase inhibitors (TKI) targeting the epidermal growth factor receptor (EGFR) have significantly prolonged survival in EGFR-mutant non-small cell lung cancer patients. However, the development of resistance mechanisms prohibits the curative potential of EGFR TKIs. Combination therapies emerge as a valuable approach to preventing or delaying disease progression. Here, we investigated the combined inhibition of polo-like kinase 1 ...
Simvastatin and the Rho-kinase inhibitor Y-27632 prevent myofibroblast transformation in Peyronie's disease-derived fibroblasts via inhibition of YAP/TAZ nuclear translocation KU Leuven
OBJECTIVES: To uncover the anti-myofibroblast (MFB) properties of Rho-kinase inhibitor (compound Y-27632) and simvastatin in an in vitro model of Peyronie's disease (PD), a sexually debilitating disease caused by an irreversible fibrotic plaque in the penile tunica albuginea (TA). MATERIALS AND METHODS: Primary human fibroblasts (FBs) were isolated from surgically obtained TA tissue from patients with PD. To induce MFB status, cells were ...