Learn More
Protein kinases are critical components of signaling pathways and trigger various biological events. Several members of this superfamily are interesting targets for novel therapeutic approaches. All known eukaryotic protein kinases exhibit a conserved catalytic core domain with an adenosine 5'-triphosphate (ATP) binding site, which often is targeted in drug(More)
Target- and ligand-based virtual screening have emerged as resource-saving techniques that have been successfully applied to identify novel chemotypes in biologically active molecules. Eight confirmed virtual screening hits have recently been described and are discussed in this review, with focus on the workflow. These are then evaluated in the light of(More)
Additional resources and features associated with this article are available within the HTML version: • Supporting Information • Links to the 4 articles that cite this article, as of the time of this article download • Access to high resolution figures • Links to articles and content related to this article • Copyright permission to reproduce figures and/or(More)
In this paper, we compare protein- and ligand-based virtual screening techniques for identifying the ligands of four biogenic amine-binding G-protein coupled receptors (GPCRs). For the screening of the virtual compound libraries, we used (1) molecular docking into GPCR homology models, (2) ligand-based pharmacophore and Feature Tree models, (3)(More)
To gain insight into the structural determinants for the matrix metalloproteinase (MMP) family, we characterized the binding sites of 56 MMP structures and one TACE (tumor necrosis factor alpha converting enzyme) structure using molecular interaction fields (MIFs). These MIFs were produced by two approaches: the GRID force field and the knowledge-based(More)
The control of hypertension and associated cardiovascular risk factors is possible by selective inhibition of the aspartyl protease renin due to its unique position in the renin-angiotensin system. Starting from a previously disclosed series of potent and nonchiral indole-3-carboxamides, we further explored this motif by structure-based drug design guided(More)
Inhibition of matrix metalloproteases (MMPs) for the treatment of diseases, such as cancer, arthritis and other diseases associated with tissue remodeling, has become an area of intense interest in the pharmaceutical industry in recent years. Despite tremendous efforts over the last decade to explore individual members of this target family, along with(More)
Pathological nitric oxide (NO) generation in sepsis, inflammation, and stroke may be therapeutically controlled by inhibiting NO synthases (NOS). Here we targeted the (6R)-5,6,7,8-tetrahydro-l-biopterin (H(4)Bip)-binding site of NOS, which, upon cofactor binding, maximally increases enzyme activity and NO production from substrate l-arginine. The first(More)
The family of nitric oxide synthases (NOS) catalyzes the conversion of L-arginine to L-citrulline and nitric oxide (NO), an important cellular messenger molecule which has been implicated in the pathophysiology of septic shock and inflammatory and neurodegenerative disease states. NOS can be maximally activated by the ubiquitous cofactor,(More)
The family of homodimeric nitric oxide synthases (NOS I-III) catalyzes the generation of the cellular messenger nitric oxide (NO) by oxidation of the substrate L-arginine. The rational design of specific NOS inhibitors is of therapeutic interest in regulating pathological NO levels associated with sepsis, inflammatory, and neurodegenerative diseases. The(More)