A5037817637- Histone Deacetylase Inhibitors Research
- Chemical Synthesis and Analysis
- Enzyme Production and Characterization
- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Click Chemistry and Applications
- Cell Adhesion Molecules Research
- Protein Degradation and Inhibitors
- Reproductive Biology and Fertility
- Sperm and Testicular Function
- Signaling Pathways in Disease
- Phytochemistry and Bioactivity Studies
- Nuclear Structure and Function
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Ubiquitin and proteasome pathways
- Microbial Metabolism and Applications
- Microbial Metabolic Engineering and Bioproduction
- GABA and Rice Research
- Synthesis and Characterization of Pyrroles
- Microbial Metabolites in Food Biotechnology
- Synthetic Organic Chemistry Methods
- Enzyme Structure and Function
University of Bonn
2024-2025
Fraunhofer Institute for Cell Therapy and Immunology
2018-2023
Histone deacetylase 6 (HDAC6) is an emerging drug target to treat oncological and non-oncological conditions. Since highly selective HDAC6 inhibitors display limited anticancer activity when used as single agent, they usually require combination therapies with other chemotherapeutics. In this work, we synthesized a mini library of analogues the preferential inhibitor HPOB in only two steps via Ugi four-component reaction key step. Biochemical HDAC inhibition cell viability assays led...
In this work, we designed, synthesized, and evaluated two types of multineurotargeting compounds using a pharmacophore merging strategy, aiming to develop potential treatments for Alzheimer's disease. We combined belinostat, an FDA-approved unselective histone deacetylase (HDAC) inhibitor, with the 5-substituted indole core contilisant, known its antioxidant neuroprotective properties as well potent inhibitory activity against monoamine oxidases (MAOs), acetylcholinesterase (AChE),...
Histone deacetylase 6 (HDAC6) is an important drug target for the treatment of cancer, inflammation, and neurodegenerative disorders. In recent years, development proteolysis-targeting chimeras (PROTACs) has emerged to achieve chemical knockdown HDAC6. Consequently, there urgent need develop efficient methods engagement studies enable a thorough characterization degradation efficiency kinetics HDAC6 PROTACs. this work, we present simple NanoBRET assay assess cellular using HeLaHDAC6-HiBiT...
Abstract Metalloproteinases of the astacin family are drawing ever increasing attention as potential drug targets. However, knowledge regarding inhibitors thereof is limited in most cases. Crucial for development metalloprotease high selectivity, to avoid side effects brought about by inhibition off‐target proteases and interference with physiological pathways. In this study we aimed at design novel selective proteinase meprin α. Based on a recently identified tertiary amine scaffold, series...
Histone deacetylase 6 (HDAC6) is an emerging drug target to treat oncological and non-oncological conditions. Since highly selective HDAC6 inhibitors display limited anticancer activity when used as single agent, they usually require combination therapies with other chemotherapeutics. In this work, we synthesized a mini library of analogues the preferential inhibitor HPOB in only two steps via Ugi four-component reaction key step. Biochemical HDAC inhibition cell viability assays led...
Astacin metalloproteinases, in particular meprins α and β, as well ovastacin, are emerging drug targets. Drug-discovery efforts have led to the development of first potent selective inhibitors last few years. However, most recent compounds based on a highly flexible tertiary amine scaffold that could cause metabolic liabilities or decreased potency due entropic penalty upon binding target. Thus, aim this study was discover novel conformationally constrained scaffolds starting points for...
Histone deacetylase 6 (HDAC6) is an emerging drug target to treat oncological and non-oncological conditions. Since highly selective HDAC6 inhibitors display limited anticancer activity when used as single agent, they usually require combination therapies with other chemotherapeutics. In this work, we synthesized a mini library of analogues the preferential inhibitor HPOB in only two steps via Ugi four-component reaction key step. Biochemical HDAC inhibition cell viability assays led...
Targeting metalloproteinases has been in the focus of drug design for a long time. However, meprin α and β emerged as potential targets just recently are linked to several diseases with different pathological background. Nevertheless, validation meprins suitable still requires highly potent selective inhibitors chemical probes elucidate their role pathophysiology. Albeit have already reported, only modest activity or selectivity known. Starting from reported heteroaromatic scaffolds, aim...
Abstract Despite huge progress in hormonal therapy and improved vitro fertilization methods, the success rates infertility treatment are still limited. A recently discovered mechanism revealed interplay between plasma protein fetuin‐B cortical granule‐based proteinase ovastacin to be a novel key regulation of fertilization. Upon sperm–egg fusion, cleavage distinct zona pellucida component by destroys sperm receptor, enhances robustness, eventually provides definitive block against...
Epigenetic drug targets have become an important focus in discovery. One of the key mechanisms epigenetics is acetylation and deacetylation histone proteins. In this study, we synthesized evaluated novel deacetylase (HDAC) inhibitors derived from clinical candidate quisinostat. A library 16 compounds categorized three chemotypes was rapidly generated using multicomponent reactions (MCRs), enabling efficient structure-activity relationship studies. The were for their activity against...
Epigenetic drug targets have become an important focus in discovery. One of the key mechanisms epigenetics is acetylation and deacetylation histone proteins. In this study, we synthesized evaluated novel deacetylase (HDAC) inhibitors derived from clinical candidate quisinostat. A library 16 compounds categorized three chemotypes was rapidly generated using multicomponent reactions (MCRs), enabling efficient structure-activity relationship studies. The were for their activity against...
In this study, we synthesized and evaluated novel histone deacetylase (HDAC) inhibitors derived from the clinical candidate quisinostat. A library of 16 compounds categorized in three chemotypes was rapidly generated using multicomponent reactions (MCRs), enabling efficient structure-activity relationship studies. First, were for their activity against Plasmodium falciparum strains 3D7 Dd2, main malaria-causing parasite, identifying compound 18b type C series as most potent. It demonstrated...
Despite huge progress in hormonal therapy and improved vitro fertilization methods, the success rates infertility treatment are still limited. A recently discovered mechanism revealed interplay between plasma protein fetuin-B cortical granule-based proteinase ovastacin as novel key-mechanism regulation of fertilization. Upon sperm-egg fusion, cleavage a distinct zona pellucida component by destroys sperm receptor, enhances robustness eventually provides definitive block against polyspermy....
<p>Despite huge progress in hormonal therapy and improved vitro fertilization methods, the success rates infertility treatment are still limited. A recently discovered mechanism revealed interplay between plasma protein fetuin-B cortical granule-based proteinase ovastacin as novel key-mechanism regulation of fertilization. Upon sperm-egg fusion, cleavage a distinct zona pellucida component by destroys sperm receptor, enhances robustness eventually provides definitive block against...
Targeting metalloproteinases has been in focus of drug design for a long time. However, human proteinases the astacin family, particular meprin α and β emerged as potential targets just recently. More more data links them to several diseases with different pathological background. Nevertheless, validation meprins suitable requires highly potent selective inhibitors chemical probes elucidate their role pathophysiology. Albeit have already reported, only modest activity or selectivity are...