A5055328126- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Computational Drug Discovery Methods
- Epigenetics and DNA Methylation
- Sirtuins and Resveratrol in Medicine
- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
- Autophagy in Disease and Therapy
- Cancer-related gene regulation
- Click Chemistry and Applications
- Synthesis and biological activity
- Cholinesterase and Neurodegenerative Diseases
- PARP inhibition in cancer therapy
- Parasites and Host Interactions
- Microbial Natural Products and Biosynthesis
- Ethnobotanical and Medicinal Plants Studies
- Chemical Synthesis and Analysis
- Receptor Mechanisms and Signaling
- HIV/AIDS drug development and treatment
- Neuroblastoma Research and Treatments
- Neuroscience and Neuropharmacology Research
- Calcium signaling and nucleotide metabolism
- Cancer, Hypoxia, and Metabolism
- Pharmacological Receptor Mechanisms and Effects
- Cancer-related Molecular Pathways
Martin Luther University Halle-Wittenberg
2016-2025
Stiftung des öffentlichen Rechts an der Martin-Luther-Universität Halle-Wittenberg
2024-2025
Wittenberg University
2025
Luther University
2004-2024
Medicina
2021-2022
University Hospital Münster
2020
Francke Foundations
2016
University of Freiburg
2006-2015
University of Buea
2014-2015
University of Douala
2014
The stem cell factor receptor, KIT, is a target for the treatment of cancer, mastocytosis, and inflammatory diseases. Here, we characterise in vitro vivo profiles masitinib (AB1010), novel phenylaminothiazole-type tyrosine kinase inhibitor that targets KIT.In vitro, had greater activity selectivity against KIT than imatinib, inhibiting recombinant human wild-type with an half inhibitory concentration (IC(50)) 200+/-40 nM blocking factor-induced proliferation phosphorylation IC(50) 150+/-80...
Abstract Deregulation of the ubiquitin/proteasome system has been implicated in pathogenesis many human diseases, including cancer. Ubiquitin-specific proteases (USP) are cysteine involved deubiquitination protein substrates. Functional connections between USP7 and essential viral proteins oncogenic pathways, such as p53/Mdm2 phosphatidylinositol 3-kinase/protein kinase B networks, strongly suggest that targeting with small-molecule inhibitors may be useful for treatment cancers diseases....
Abstract Sirtuins are a highly conserved class of NAD + -dependent lysine deacylases. The human isotype Sirt2 has been implicated in the pathogenesis cancer, inflammation and neurodegeneration, which makes modulation activity promising strategy for pharmaceutical intervention. A rational basis development optimized inhibitors is lacking so far. Here we present high-resolution structures complex with selective drug-like that show unique inhibitory mechanism. Potency unprecedented selectivity...
Here we report the development of a proteolysis targeting chimera (PROTAC) based on combination unique features sirtuin rearranging ligands (SirReals) as highly potent and isotype-selective Sirt2 inhibitors with thalidomide, bona fide cereblon ligand. For first time, formation PROTAC by Cu(I)-catalyzed cycloaddition thalidomide-derived azide to an alkynylated inhibitor. This well versatile linking strategy can be readily adapted other targets. In HeLa cells, our SirReal-based induced...
Computer-aided drug design (CADD) often involves virtual screening (VS) of large compound datasets and the availability such is vital for discovery protocols. We assess bioactivity "drug-likeness" a relatively small but structurally diverse dataset (containing >1,000 compounds) from African medicinal plants, which have been tested proven wide range biological activities. The geographical regions collection plants cover entire continent Africa, based on data literature sources information...
Suramin is a symmetric polyanionic naphthylurea originally used for the treatment of trypanosomiasis and onchocerciasis. diverse analogues exhibit broad range biological actions in vitro vivo, including, among others, antiproliferative antiviral activity. derivatives usually target purinergic binding sites. Class III histone deacetylases (sirtuins) are amidohydrolases that require nicotinamide adenine dinucleotide (NAD(+)) as cofactor their catalytic mechanism(.) Deacetylation proteins leads...
The treatment of schistosomiasis, a disease caused by blood flukes parasites the Schistosoma genus, depends on intensive use single drug, praziquantel, which increases likelihood development drug-resistant parasite strains and renders search for new drugs strategic priority. Currently, inhibitors human epigenetic enzymes are actively investigated as novel anti-cancer have potential to be used anti-parasitic agents. Here, we report that mansoni histone deacetylase 8 (smHDAC8), most expressed...
NAD+-dependent histone deacetylases (sirtuins) are enzymes that cleave acetyl groups from lysines in histones and other proteins. Potent selective sirtuin inhibitors interesting tools for the investigation of biological functions those may be future drugs treatment cancer. Splitomicin was among first two were discovered yeast sirtuins but showed rather weak inhibition on human enzymes. We present detailed structure–activity relationships splitomicin derivatives their recombinant Sirt2. To...
Natural products (NPs) are often regarded as sources of drugs or drug leads simply a "source inspiration" for the discovery novel drugs. We have built Northern African Products Database (NANPDB) by collecting information on ∼4500 NPs, covering literature data period from 1962 to 2016. The cover compounds isolated mainly plants, with contributions some endophyte, animal (e.g., coral), fungal, and bacterial sources. were identified 617 source species, belonging 146 families. Computed...
Malaria is currently a public health concern in many countries the world due to various factors which are not yet under check. Drug discovery projects targeting malaria often resort natural sources search for lead compounds. A survey of literature has led summary major findings regarding plant-derived compounds from African flora, have shown anti-malarial/antiplasmodial activities, tested by vitro and vivo assays. Considerations been given with activities ranging "very active" "weakly...
Schistosomiasis is a major neglected parasitic disease that affects more than 265 million people worldwide and for which the control strategy consists of mass treatment with only available drug, praziquantel. In this study, series new benzohydroxamates were prepared as potent inhibitors Schistosoma mansoni histone deacetylase 8 (smHDAC8). Crystallographic analysis provided insights into inhibition mode smHDAC8 activity by these 3-amidobenzohydroxamates. The newly designed evaluated in...
Abstract We have previously described novel histone acetyltransferase (HAT) inhibitors that block neuroblastoma cell growth in vitro . Here we show two selected pyridoisothiazolone HAT inhibitors, PU139 and PU141, induce cellular hypoacetylation inhibit of several neoplastic lines originating from different tissues. Broader selectivity profiling shows blocks the HATs Gcn5, p300/CBP-associated factor (PCAF), CREB (cAMP response element-binding) protein (CBP) p300, whereas PU141 is selective...
Histone deacetylase 6 (HDAC6) catalyzes the removal of an acetyl group from lysine residues several non-histone proteins. Here we report preparation thiazole-, oxazole-, and oxadiazole-containing biarylhydroxamic acids by a short synthetic procedure. We identified them as selective HDAC6 inhibitors investigating inhibition recombinant HDAC enzymes protein acetylation in cells Western blotting (tubulin vs histone acetylation). The most active compounds exhibited nanomolar potency high...
Metal-dependent histone deacetylases (HDACs) are key epigenetic regulators that represent promising therapeutic targets for the treatment of numerous human diseases. Yet currently FDA-approved HDAC inhibitors nonspecifically target at least several 11 structurally similar but functionally different isozymes, which hampers their broad usage in clinical settings. Selective targeting single isozymes being developed, precise understanding molecular terms selectivity remains sparse. Here, we show...