Showing papers by "Michael Hennig published in 2008"
TL;DR: A structural model involving a ligand-induced relative movement of the kinase domain resulting in a more compact heterotrimer and a conformational change in the Kinase domain that protects AMPK from dephosphorylation of Thr172 is proposed, thus positively affecting AMPK activity.
97 citations
TL;DR: Biodistribution studies in nude mice bearing an AR4-2J tumour or a transfected HEK-sst2 cell-based tumour showed high and specific uptake in the tumour and in other sst-receptor-expressing tissues, which reflects the high receptor binding affinity and the high rate of internalisation.
Abstract: Somatostatin-based radioligands have been shown to have sensitive imaging properties for neuroendocrine tumours and their metastases. The potential of [(55)Co(dotatoc)] (dotatoc =4,7,10-tricarboxymethyl-1,4,7,10-tetraazacyclododecane-1-ylacetyl-D-Phe-(Cys-Tyr-D-Trp-Lys-Thr-Cys)-threoninol (disulfide bond)) as a new radiopharmaceutical agent for PET has been evaluated. (57)Co was used as a surrogate of the positron emitter (55)Co and the pharmacokinetics of [(57)Co(dotatoc)] were investigated by using two nude mouse models. The somatostatin receptor subtype (sst1-sst5) affinity profile of [(nat)Co(dotatoc)] on membranes transfected with human somatostatin receptor subtypes was assessed by using autoradiographic methods. These studies revealed that [(57)Co(dotatoc)] is an sst2-specific radiopeptide which presents the highest affinity ever found for the sst2 receptor subtype. The rate of internalisation into the AR4-2J cell line also was the highest found for any somatostatin-based radiopeptide. Biodistribution studies, performed in nude mice bearing an AR4-2J tumour or a transfected HEK-sst2 cell-based tumour, showed high and specific uptake in the tumour and in other sst-receptor-expressing tissues, which reflects the high receptor binding affinity and the high rate of internalisation. The pharmacologic differences between [(57)Co(dotatoc)] and [(67)Ga(dotatoc)] are discussed in terms of the structural parameters found for the chelate models [Co(II)(dota)](2-) and [Ga(III)(dota)](-) whose X-ray structures have been determined. Both chelates show six-fold coordination in pseudo-octahedral arrangements.
65 citations
TL;DR: Fragment screening revealed that tyramine binds to the active site of the Alzheimer's disease drug target BACE-1 and structure-guided ligand design led to the synthesis of further low molecular weight compounds that are starting points for chemical leads.
52 citations
TL;DR: An optimized pre-organization of the pharmacophores could be realized, leading to antagonists with improved affinities, and the replacement of NeuNAc by bulky (R)- and (S)-adamantyl-lactic acid was studied, which showed a slightly reduced affinity.
9 citations
Patent•
23 Dec 2008TL;DR: The present invention relates to polymorphic forms of Oseltamivir phosphate, especially the (3R,4R,5S) -5-amino-4-acetylamino-3-(1-ethyl-propoxy)-cyclohex-1-ene-carboxylic acid ethyl ester phosphate, which is a potent inhibitor of viral neuraminidase as discussed by the authors.
Abstract: The present invention relates to polymorphic forms of Oseltamivir phosphate, especially the (3R,4R,5S) -5-amino-4-acetylamino-3-(1-ethyl-propoxy)-cyclohex-1-ene-carboxylic acid ethyl ester phosphate, which is a potent inhibitor of viral neuraminidase.
2 citations