A5047867480- Estrogen and related hormone effects
- Computational Drug Discovery Methods
- 14-3-3 protein interactions
- Neurobiology and Insect Physiology Research
- Microbial Natural Products and Biosynthesis
- Cholinesterase and Neurodegenerative Diseases
- Enzyme Structure and Function
- Pharmacogenetics and Drug Metabolism
- Radiopharmaceutical Chemistry and Applications
- Circadian rhythm and melatonin
- Bone health and treatments
- Natural product bioactivities and synthesis
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Cancer therapeutics and mechanisms
- Bioactive Compounds and Antitumor Agents
- Adipose Tissue and Metabolism
- Mass Spectrometry Techniques and Applications
- bioluminescence and chemiluminescence research
- Cytomegalovirus and herpesvirus research
- MicroRNA in disease regulation
- Boron Compounds in Chemistry
- Ferrocene Chemistry and Applications
- Biochemical and Molecular Research
Czech Academy of Sciences, Institute of Molecular Genetics
2013-2025
Czech Academy of Sciences
2005-2024
Institute of Molecular Genetics
2024
Institute of Entomology
2024
Česká Zbrojovka (Czechia)
2019
University of California, Berkeley
2004-2007
University of California, Davis
2004
Accumulation of senescent cells in tissues with advancing age participates the pathogenesis several human age-associated diseases. Specific secretome, resistance to apoptotic stimuli, and lack immune system response contribute accumulation their adverse effects tissues. Inhibition antiapoptotic machinery, augmented cells, by BCL-2 protein family inhibitors represents a promising approach eliminate from This study aimed explore synergistic selective senolytic anti-apoptotic targeting...
Silychristin is the second most abundant flavonolignan (after silybin) present in fruits of Silybum marianum. A group compounds containing silychristin (3) and its derivatives such as 2,3-dehydrosilychristin (4), 2,3-dehydroanhydrosilychristin (5), anhydrosilychristin (6), silyhermin (7), isosilychristin (8) were studied. Physicochemical data these acquired at high resolution compared. The absolute configuration (7) was proposed to be identical (3a) ring D (10R,11S). preparation (4)...
Steroid hormone receptors represent a major target in drug discovery. As ligand inducible transcription factors, their activity can be modulated by small lipophilic molecules. Here we describe two panels of potent and selective luciferase reporter cell lines based on cells with low endogenous steroid receptor (U2OS). The contain for estrogen α β, androgen, glucocorticoid, mineralocorticoid, progesterone receptors. In the first panel, activation either synthetic, response elements containing...
Selective agonism of the estrogen receptor (ER) subtypes, ERα and ERβ, has historically been difficult to achieve due high degree ligand-binding domain structural similarity. Multiple efforts have focused on use classical organic scaffolds model 17β-estradiol geometry in design ERβ selective agonists, with several proceeding various stages clinical development. Carborane offer many unique advantages including potential for novel ligand/receptor interactions but remain relatively unexplored....
Objective: In search of efficient anticancer agents, we aimed at the design and synthesis a library tetrasubstituted alkenes. These are structural analogues tamoxifen, one widely used therapeutics. Methods: Our small organic compound was prepared via chemical in solution using Larock three-component coupling reaction, which is known to tolerate diverse functional groups. Further, have integrated this synthetic approach four- fivecomponent alkene assembly by Sonogashira coupling, A3 AHA...
The increase in the number of bacterial strains resistant to known antibiotics is alarming. In this study we report synthesis novel compounds termed Lipophosphonoxins II (LPPO II). We show that LPPO display excellent activities against Gram-positive and -negative bacteria, including pathogens multiresistant strains. describe their mechanism action-plasmatic membrane pore-forming activity selective for bacteria. Importantly, neither damage nor cross eukaryotic plasmatic at bactericidal...
We report for the first time an autosomal recessive inborn error of de novo purine synthesis (DNPS)-PAICS deficiency. investigated two siblings from Faroe Islands born with multiple malformations resulting in early neonatal death. Genetic analysis affected individuals revealed a homozygous missense mutation PAICS (c.158A>G; p.Lys53Arg) that affects structure catalytic site bifunctional enzyme phosphoribosylaminoimidazole carboxylase (AIRC, EC 4.1.1.21)/phosphoribosylaminoimidazole...
Juvenile hormones (JHs) control insect metamorphosis and reproduction. JHs act through a receptor complex consisting of methoprene-tolerant (Met) taiman (Tai) proteins to induce transcription specific genes. Among chemically diverse synthetic JH mimics (juvenoids), some which serve as insecticides, unique peptidic juvenoids stand out being highly potent yet exquisitely selective family true bugs. Their mode action is unknown. Here we demonstrate that, like established agonists, upon the JHR...
Despite intensive research efforts, the distinct biological roles of two closely related estrogen receptors, ERα and ERβ, are only partially understood. Therefore, ligands selective for either isotypes useful tools because they allow exerting a desired subset effects mediated by one receptors. Here we report on synthesis new class potent represented series 17α-substituted estradiols bearing lipophilic perfluoroalkyl chains. These 17α-perfluoroalkylated were synthesized Ru-catalyzed cross...
To identify novel estrogen receptor ligands a series of substituted 17α-arylestradiols were synthesized using the catalytic [2 + 2 2]cyclotrimerization 17α-ethynylestradiol with various 1,7-diynes in presence Wilkinson's catalysts [Rh(PPh3)3Cl]. The compounds subjected to competitive binding assays, cell-based luciferase reporter and proliferation assays. These experiments confirmed their estrogenic character revealed some interesting properties like mixed partial/full agonism for ERα/ERβ...
MicroRNAs (miRNAs) are small RNAs repressing gene expression. They contribute to many physiological processes and pathologies. Consequently, strategies for manipulation of the miRNA pathway interest as they could provide tools experimental or therapeutic interventions. One such be chemical compounds identified through high-throughput screening (HTS) with reporter assays. While a number have been in screens, their application potential remains elusive. Here, we report our experience...
Abstract Transcription factors of the bHLH-PAS family play vital roles in animal development, physiology, and disease. Two members require binding low-molecular weight ligands for their activity: vertebrate aryl hydrocarbon receptor (AHR) insect juvenile hormone (JHR). In fly Drosophila melanogaster , paralogous proteins GCE MET constitute ligand-binding component JHR complexes. Whilst GCE/MET AHR are phylogenetically heterologous, mode action is similar. targeted by several synthetic...
Computational exploration of chemical space is crucial in modern cheminformatics research for accelerating the discovery new biologically active compounds. In this study, we present a detailed analysis library potential glucocorticoid receptor (GR) ligands generated by molecular generator, Molpher. To generate targeted GR and to construct classification models, structures from ChEMBL database as well internal IMG library, that was experimentally screened biological activity primary...
Computational exploration of chemical space is crucial in modern cheminformatics research for accelerating the discovery new biologically active compounds. In this study, we present a detailed analysis library potential glucocorticoid receptor (GR) ligands generated by molecular generator, Molpher. To generate targeted GR and construct classification models, structures from ChEMBL database as well internal IMG library, which was experimentally screened biological activity primary luciferase...