A5022888378- Computational Drug Discovery Methods
- Receptor Mechanisms and Signaling
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Protein Structure and Dynamics
- Pharmacogenetics and Drug Metabolism
- Neuropeptides and Animal Physiology
- Neuroscience and Neuropharmacology Research
- Cytokine Signaling Pathways and Interactions
- Monoclonal and Polyclonal Antibodies Research
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Peptidase Inhibition and Analysis
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Analytical Chemistry and Chromatography
- Crystallography and molecular interactions
- thermodynamics and calorimetric analyses
- Pharmacological Receptor Mechanisms and Effects
- Protein Degradation and Inhibitors
- Microbial Natural Products and Biosynthesis
- Asymmetric Synthesis and Catalysis
- Chemical synthesis and alkaloids
- Natural product bioactivities and synthesis
- Hemoglobin structure and function
- Innovative Microfluidic and Catalytic Techniques Innovation
HUN-REN Research Centre for Natural Sciences
2016-2025
Budapest University of Technology and Economics
2009-2025
Medicina
2015-2025
Centre for Drug Research and Development
2022-2025
Institute of Molecular Life Sciences
2001-2023
University of Pecs
2022
Institute of Organic Chemistry
1997-2020
Budapest Business University
2015-2020
Hungarian Academy of Sciences
1995-2018
Gedeon Richter (Hungary)
2006-2015
Abstract COVID-19, caused by SARS-CoV-2, lacks effective therapeutics. Additionally, no antiviral drugs or vaccines were developed against the closely related coronavirus, SARS-CoV-1 MERS-CoV, despite previous zoonotic outbreaks. To identify starting points for such therapeutics, we performed a large-scale screen of electrophile and non-covalent fragments through combined mass spectrometry X-ray approach SARS-CoV-2 main protease, one two cysteine viral proteases essential replication. Our...
G protein-coupled receptors (GPCRs) form both the largest family of membrane proteins and drug targets, mediating action one-third medicines. The GPCR database, GPCRdb serves >4 000 researchers every month offers reference data, analysis own or literature experiment design dissemination published datasets. Here, we describe new updated resources with a particular focus on integration sequence, structure function. contains all human non-olfactory GPCRs (and >27 orthologs), G-proteins...
Fragment-based drug discovery (FBDD) is well suited for discovering both leads and chemical probes of protein function; it can cover broad swaths space allows the use creative chemistry. FBDD widely implemented lead in industry but sometimes used less systematically academia. Design principles implementation approaches fragment libraries are continually evolving, lack up-to-date guidance may prevent more effective application This Perspective explores many theoretical, practical, strategic...
G protein-coupled receptors (GPCRs) are physiologically abundant signaling hubs routing hundreds of extracellular signal substances and drugs into intracellular pathways. The GPCR database, GPCRdb supports >5000 interdisciplinary researchers every month with reference data, analysis, visualization, experiment design dissemination. Here, we present our fifth major release setting out an overview the many resources for receptor sequences, structures, ligands. This includes recently published...
Lipophilic efficiency indices such as LLE and LELP were suggested to support balanced optimization of potency ADMET profile. Here we investigated the performance on multiple data sets representing different stages drug discovery including fragment HTS hits leads, development candidates, phase II compounds, launched drugs. Analyzing their impact ADME safety properties binding thermodynamics, found that both help identifying better quality compounds. is sensible for but does not prefer...
The transcription factor STAT5 is an essential downstream mediator of many tyrosine kinases (TKs), particularly in hematopoietic cancers. activated by FLT3-ITD, which a constitutively active TK driving the pathogenesis acute myeloid leukemia (AML). Since critical diverse malignant properties AML cells, direct targeting significant clinical value. Here, we describe development and preclinical evaluation novel, potent SH2 domain inhibitor, AC-4-130, can efficiently block pathological levels...
In contrast to designed polypharmacology that can result in efficient drugs for complex disorders, unintended drug promiscuity has detrimental contribution side effects and toxicology. Characterization of promiscuous compounds enhances the understanding interaction patterns aids design with broader selectivity against off-targets a major impact on medicinal chemistry outcome. this Miniperspective we provide insights effect physicochemical parameters promiscuity. Information collected from...
A recent viewpoint article (Improving the plausibility of success with inefficient metrics. ACS Med. Chem. Lett. 2014, 5, 2-5) argued that standard definition ligand efficiency (LE) is mathematically invalid. In this viewpoint, we address criticism and show categorically LE valid. other metrics such as lipophilic (LLE) can be useful during multiparameter optimization challenge faced by medicinal chemists.
Increased interest in covalent drug discovery led to the development of computer programs predicting binding mode and affinity inhibitors. Here we compare performance six docking tools, AutoDock4, CovDock, FITTED, GOLD, ICM-Pro, MOE, for reproducing experimental modes an unprecedently large diverse set complexes. It was found that 40–60% top scoring ligand poses are within 2.0 Å RMSD from mode. This rate showed program dependent increase achieved 50–90% when best among ten considered. is...
Beyond rule-of-five (bRo5) compounds are increasingly used in drug discovery. Here we analyze 37 target proteins that have bRo5 drugs or clinical candidates. Targets can benefit from if they "complex" hot spot structure with four more hots spots, including some strong ones. Complex I targets show positive correlation between binding affinity and molecular weight. These conventionally druggable, but reaching additional spots enables improved pharmaceutical properties. II targets, mostly...
Two interesting new X-ray structures of negative allosteric modulator (NAM) ligands for the mGlu5 receptor, M-MPEP (3) and fenobam (4), are reported. The show how binding induces different receptor water channel conformations to previously published structures. structure fenobam, where a urea replaces acetylenic linker in mavoglurant, reveals mode ligand is rotated by 180° compared proposed docking model. need multiple accurate GPCR structure-based drug design demonstrated growing vectors...
Abstract Two-thirds of signaling substances, several sensory stimuli and over one-third drugs act via receptors coupling to G proteins. Here, we present an online platform for protein research with reference data tools analysis, visualization design scientific studies across disciplines areas. This may help translate new pharmacological, structural genomic into insights on vital human physiology medicine. The database is accessible at https://gproteindb.org.
Abstract G protein-coupled receptors (GPCRs) are membrane-spanning transducers mediating the actions of numerous physiological ligands and drugs. The GPCR database GPCRdb supports a large global research community with reference data, analysis, visualization, experiment design dissemination. Here, we describe our sixth major release starting an overview all resources for ligands. As addition, ∼400 human odorant their orthologs in model organisms can now be studied across various data tool...
The docking accuracy of Glide was evaluated using 16 different protocols on 190 protein−fragment complexes representing 78 targets. Standard precision (Glide SP) based showed the best performance. average root-mean-square deviation (rmsd) between docked and cocrystallized poses achieved by SP with pre- postprocessing 1.17 Å, an acceptable binding mode rmsd < 2 Å could be found in 80% cases. Comparison results produced suggests that sampling efficacy is adequate for fragment docking. seems to...