A5044326924- Histone Deacetylase Inhibitors Research
- Peptidase Inhibition and Analysis
- Computational Drug Discovery Methods
- Signaling Pathways in Disease
- Synthesis and Catalytic Reactions
- Crystallization and Solubility Studies
- Biochemical and Molecular Research
- X-ray Diffraction in Crystallography
- Cholinesterase and Neurodegenerative Diseases
- Enzyme function and inhibition
- Chemical Reaction Mechanisms
- Click Chemistry and Applications
- Synthesis and biological activity
- Advanced Breast Cancer Therapies
- Pharmacological Receptor Mechanisms and Effects
- Chemical Synthesis and Analysis
- Metal complexes synthesis and properties
- Cancer therapeutics and mechanisms
- Protein Degradation and Inhibitors
- Magnetism in coordination complexes
- Cancer Mechanisms and Therapy
- Alzheimer's disease research and treatments
- Enzyme Structure and Function
- Oxidative Organic Chemistry Reactions
- Multicomponent Synthesis of Heterocycles
Martin Luther University Halle-Wittenberg
2022-2025
Stiftung des öffentlichen Rechts an der Martin-Luther-Universität Halle-Wittenberg
2024-2025
Napo Pharmaceuticals (United States)
2016
October 6 University
2016
Hypoxia in tumors contributes to chemotherapy resistance, worsened by acidosis driven carbonic anhydrases (
HDAC11 is a class IV histone deacylase with no crystal structure reported so far. The catalytic domain of shares low sequence identity other HDAC isoforms, which makes conventional homology modeling less reliable. AlphaFold machine learning approach that can predict the 3D proteins high accuracy even in absence similar structures. However, fact models are predicted small molecules and ions/cofactors complicates their utilization for drug design. Previously, we optimized an model by adding...
HDAC11 is a class IV histone deacylase with no crystal structure reported so far. The catalytic domain of shares low sequence identity other HDAC isoforms which makes the conventional homology modeling less reliable. AlphaFold neural network machine learning approach that can predict 3D proteins high accuracy even in absence similar structures. However fact models are predicted small molecules and ions/cofactors complicate their utilization for drug design. Previously we optimized an model...
Histone deacetylase 11 (HDAC11), an enzyme that cleaves acyl groups from acylated lysine residues, is the sole member of class IV HDAC family with no reported crystal structure so far. The catalytic domain HDAC11 shares low sequence identity other isoforms which complicates conventional template-based homology modeling. AlphaFold a neural network machine learning approach for predicting 3D structures proteins atomic accuracy even in absence similar structures. However, predicted by are...
The therapeutic potential of HDAC inhibitors containing a hydroxamic acid moiety as zinc-binding group (ZBG) is limited in clinical use due to their mutagenicity. In addition, acids often exhibit off-target effects that can lead undesirable toxicity. Therefore, the development with alternative ZBGs has proven be promising approach overcome these drawbacks. carrying alkyl hydrazide ZBG have recently been published selective for different subtypes. present study, ligand-based virtual screening...
Novel tropane-based compounds were synthesized exhibiting antiproliferative properties against HepG2 and MCF7 carcinoma cell lines.
AlphaFold is an artificial intelligence approach for predicting the 3D structures of proteins with atomic accuracy. One challenge that limits use models drug discovery correct prediction folding in absence ligands and cofactors, which compromises their direct use. We have previously described optimization HDAC11-AlphaFold model docking selective inhibitors such as FT895 SIS17. Based on predicted binding mode optimized HDAC11 model, a new scaffold was designed, resulting compounds were tested...
AlphaFold is an artificial intelligence approach for predicting the three-dimensional (3D) structures of proteins with atomic accuracy. One challenge that limits use models drug discovery correct prediction folding in absence ligands and cofactors, which compromises their direct use. We have previously described optimization histone deacetylase 11 (HDAC11) model docking selective inhibitors such as FT895 SIS17. Based on predicted binding mode optimized HDAC11 model, a new scaffold was...
In a fragment-based approach using NMR spectroscopy, benzyloxyacetohydroxamic acid-derived inhibitors of the bacterial deacetylase LpxC bearing substituent to target uridine diphosphate-binding site enzyme were developed. By appending privileged fragments via suitable linker, potent with promising antibacterial activities could be obtained, like one-digit nanomolar inhibitor (
3‐(2,4‐Dichlorophenyl)‐7‐[(2,4‐dichlorophenyl)methylidene]‐11‐methyl‐4‐phenyl‐4,5,11‐triazatricyclo[6.2.1.0*2,6*]undec‐5‐ene ( 3 ) was synthesized in a stereoselective manner. Single crystal X‐ray study of revealed that the structure belongs to triclinic system with space group . The is further stabilized by an intermolecular CH … π interaction. Molecular mechanics force field (MM + ), followed either semi‐empirical AM1 or PM3, used calculate optimized geometrical parameters determined...
Structure-based pharmacophores were generated and validated using the bioactive conformations of different co-crystallized enzyme-inhibitor complexes for allosteric palm-1 thumb-2 inhibitors NS5B. Two pharmacophore models obtained, one with sensitivity = 0.929 specificity 0.983, other 1 0.979. In addition, a quantitative structure activity relationship (QSAR) developed based on values scoring functions as descriptors predicting both binding sites (palm-1 thumb-2). QSAR studies revealed good...
Histone deacetylase 11 (HDAC11), an enzyme that is cleaving acyl groups from acylated lysine residues, the sole member of class IV HDAC family with no reported crystal structure so far. The catalytic domain HDAC11 shares low sequence identity other isoforms which complicates conventional template based homology modeling. AlphaFold a neural network machine learning approach for predicting 3D structures proteins atomic accuracy even in absence similar structures. However, predicted by are...
HDAC11 is a class IV histone deacylase with no crystal structure reported so far. The catalytic domain of shares low sequence identity other HDAC isoforms which makes the conventional homology modeling less reliable. AlphaFold neural network machine learning approach that can predict 3D proteins high accuracy even in absence similar structures. However fact models are predicted small molecules and ions/cofactors complicate their utilization for drug design. Previously we optimized an model...
Abstract The scaffolds of two known CDK inhibitors (CAN508 and dinaciclib) were the starting point for synthesizing series pyarazolo[1,5‐ a ]pyrimidines to obtain potent with proper selectivity. study presented four promising compounds; 10d , 10e 16a 16c based on cytotoxic studies. Compound revealed superior activity in preliminary anticancer screening GI % = 79.02–99.13 against 15 cancer cell lines at 10 μM from NCI full panel 60 was then selected further investigation. Furthermore,...
Abstract Class I histone deacetylases (HDACs) are considered promising targets in current cancer research. To obtain subtype‐selective and potent HDAC inhibitors, we used the aminobenzamide scaffold as zinc‐binding group prepared new derivatives with a pyrazole ring linking group. The synthesized compounds were analyzed vitro using an enzymatic assay against HDAC1, −2, −3. Compounds 12b , 15b 15i found to be HDAC1 also comparison reference entinostat tacedinaline, IC 50 values of 0.93, 0.22,...
Background: Alzheimer's disease (AD) drugs in therapy are limited to acetylcholine esterase inhibitors and memantine. Newly developed against a single target structure have an insufficient effect on symptomatic AD patients. Results: Novel aromatically anellated pyridofuranes been evaluated for inhibition of AD-relevant protein kinases cdk1, cdk2, gsk-3b Fyn. Best activities found naphthopyridofuranes with hydroxyl function as part the 5-substituent hydrogen or halogen substituent 8-position....