A5080164497- Hippo pathway signaling and YAP/TAZ
- Cancer-related Molecular Pathways
- Mast cells and histamine
- Inflammatory mediators and NSAID effects
- Cytokine Signaling Pathways and Interactions
- Microtubule and mitosis dynamics
- Cellular Mechanics and Interactions
Goethe University Frankfurt
2021-2025
Benzoxazepinones have been extensively studied as exclusively selective RIP kinase 1 inhibitors. This scaffold binds a type-III inhibitor targeting the αC-out/DFG-out conformation. inactive conformation results in large expansion of back pocket, that has also reported for LIM kinases. Scaffold hopping is common design orthosteric inhibitors, but not explored allosteric mainly due to typically exclusive selectivity type III Here, we hypothesized shared structural properties LIMKs and RIPKs...
Benzoxazepinones have been extensively studied as exclusively selective RIP kinase 1 inhibitors. This scaffold binds to an allosteric pocket created by αC-out/DFG-out conformation. inactive conformation results in a large expansion of the back pocket, that has also reported for LIM kinases. Scaffold hopping is common design orthosteric inhibitors but not explored inhibitors, mainly due typically exclusive selectivity type III Here, we hypothesized shared structural properties LIMKs and RIPKs...
Abstract Selectivity for closely related isoforms of protein kinases is a major challenge in the design drugs and chemical probes. Covalent targeting unique cysteines potential strategy to achieve selectivity highly conserved binding sites. Here, we used pan-LIMK inhibitor selectively probe LIMK1 over LIMK2 by LIMK1-specific cysteine C349 located glycine-rich loop region. Binding kinetics both non-covalent covalent LIMK inhibitors were investigated, fast on-rate small size type-I inhibitor....
CASK (Ca2+/calmodulin-dependent Ser/Thr kinase) is a member of the MAGUK (membrane-associated guanylate family that functions as neurexin kinases with roles implicated in neuronal synapses and trafficking. The lack canonical DFG motif, which altered to GFG CASK, led classification pseudokinase. However, functional studies revealed can still phosphorylate substrates absence divalent metals. dysfunction has been linked many diseases, including colorectal cancer, Parkinson's disease, X-linked...