A5030233937- Prostate Cancer Treatment and Research
- PI3K/AKT/mTOR signaling in cancer
- Sulfur-Based Synthesis Techniques
- Cancer, Lipids, and Metabolism
- Lung Cancer Treatments and Mutations
- Fibroblast Growth Factor Research
- Chronic Myeloid Leukemia Treatments
- Synthesis and Catalytic Reactions
- Synthesis and Biological Evaluation
- Colorectal Cancer Treatments and Studies
- Microtubule and mitosis dynamics
- Immune cells in cancer
- Cancer Treatment and Pharmacology
- Biochemical and Molecular Research
- Cancer-related Molecular Pathways
- Tuberculosis Research and Epidemiology
- Phagocytosis and Immune Regulation
- Cancer therapeutics and mechanisms
- Chemical Reactions and Isotopes
- Protein Degradation and Inhibitors
- Lipid Membrane Structure and Behavior
- Organic and Inorganic Chemical Reactions
- Genetics, Bioinformatics, and Biomedical Research
- Liver physiology and pathology
- Macrophage Migration Inhibitory Factor
Vichem Chemie (Hungary)
2011-2024
Semmelweis University
2010-2013
Hungarian Academy of Sciences
2006-2010
Helmholtz-Zentrum Berlin für Materialien und Energie
2010
Budapest University of Technology and Economics
2006-2008
Tuberculosis (TB) is a major infectious disease associated increasingly with drug resistance. Thus, new anti-tubercular agents novel mechanisms of action are urgently required for the treatment drug-resistant TB. In prior work, we identified compound 1 (cyclohexyl(4-(isoquinolin-5-ylsulfonyl)piperazin-1-yl)methanone) and showed that its activity attributable to inhibition inosine-5′-monophosphate dehydrogenase (IMPDH) in Mycobacterium tuberculosis. present study, explored structure–activity...
Abstract Treatment-naïve small cell lung cancer (SCLC) is typically susceptible to standard-of-care chemotherapy consisting of cisplatin and etoposide recently combined with PD-L1 inhibitors. Yet, in most cases, SCLC patients develop resistance first-line therapy alternative therapies are urgently required overcome this resistance. In study, we tested the efficacy dinaciclib, an FDA-orphan drug inhibitor cyclin-dependent kinase (CDK) 9, among other CDKs, SCLC. Furthermore, report on a newly...
The Warburg effect occurs both in cancer cells and inflammatory macrophages. aim of our work was to demonstrate the role PI3K-Akt-mTOR axis HL-60 derived, rat peritoneal human blood macrophages investigate potential selected inhibitors this pathway antagonize it. M1 polarization HL-60-derived monocyte-derived supported by increased expression NOS2 cytokines. All polarized investigated expressed higher levels HIF-1α NOS2, which were reduced kinase inhibitors, supporting axis. Using Seahorse...
Background: Activated proximal tubular cells play an important role in renal fibrosis. We investigated whether sunitinib and a kidney-targeted conjugate of were capable attenuating fibrogenic events tubulointerstitial Methods: A was prepared by linkage analog (named 17864) via platinum-based linker to the kidney-specific carrier lysozyme. Pharmacological activity 17864-lysozyme evaluated human kidney (HK-2); capability kidney-directed accumulate kidneys studied mice. Potential antifibrotic...
The hepatocyte growth factor/scatter factor (HGF/SF) tyrosine kinase (TK) receptor c-Met plays a crucial role in the development of invasive phenotype tumors and thus represents an attractive candidate for targeted therapies variety malignancies, including human malignant melanoma (MM). In contrast to what has been shown previously, we were not able detect any genetic alterations, either juxtamembrane- or TK-domain c-Met, studied MM cell lines. Nevertheless, was constitutively active these...
The evaluation of the radial electron density profile a drug containing sterically stabilized liposomal system is described. Using synchrotron small-angle X-ray scattering, we were able to characterize hydrophilic shell polyethylene glycol chains. Gaussian model for describing along normal bilayer, got an asymmetric distribution PEGylated lipids in accordance with theoretical considerations. Moreover, used anomalous scattering study localization hydrophobic (a kinase inhibitor), which...
3D tissue cultures provide a more physiologically relevant context for the screening of compounds, compared with 2D cell cultures. Cells cultured in hydrogels also show complex phenotypes, increasing scope phenotypic profiling. Here we describe high-content platform that uses invasive human prostate cancer cells standard 384-well assay plates to study activity potential therapeutic small molecules and antibody biologics. Image analysis tools were developed process image data measure over 800...
Abstract The development of a macromolecular conjugate multitargeted tyrosine kinase inhibitor is described that can be used for renal‐specific delivery into proximal tubular cells. A novel sunitinib analogue, is, 17864, conjugated to NH 2 ‐PAMAM‐G3 dendrimer via the platinum (II)‐based Universal Linkage System (ULS™). activity 17864 retained after coordination ULS linker alone or when coupled ‐PAMAM‐G3. 17864‐UlS‐NH non‐toxic cells in vitro. After intravenous administration mice, rapidly...
Multikinase inhibitors are potent anticancer drugs that simultaneously intervene in multiple related signaling cascades, thus being capable of blocking salvage pathways may play a role the development drug resistance. increasingly evaluated for indications other than cancer, but long-term safety risks dictated by off-organ toxicities these agents prevent their safe and effective use. Here, we describe new approach which platinum coordination chemistry is applied cell-selective multikinase...
Abstract Prostate cancer remains a major cause of male mortality. Genetic alteration the PI3K/AKT/mTOR pathway is one key events in tumor development and progression prostate cancer, with inactivation PTEN suppressor being very common this type. Extensive evaluation has been performed on therapeutic potential inhibitors resistance mechanisms arising patients PTEN-mutant background. However, wild-type phenotype, have not demonstrated efficacy, an area clinical unmet need. In study, we...
Activating mutations in the epidermal growth factor receptor (EGFR) have been identified a subset of non-small cell lung cancer (NSCLC), which is one leading types worldwide. Application EGFR tyrosine kinase inhibitors leads to acquired resistance by secondary or amplification hepatocyte (c-Met) gene. Although several and c-Met reported, potent dual EGFR/c-Met inhibitors, can overcome this latter mechanism, hitherto not published reached clinical trials. In present study we designed novel...
Fibroblast growth factor receptor-4 (FGFR4) is a tyrosine kinase with range of important physiological functions. However, it also frequently mutated in various cancers and now generating significant interest as potential therapeutic target. Unfortunately, biochemical characterization its role disease, further evaluation drug target hampered by lack specific inhibitor. We aimed to discover new inhibitors for FGFR4 ab initio using strategy combining silico, vitro cell-based assays. used the...
Background: Anti-EGFR antibody therapy is still one of the clinical choices in head and neck squamous cell carcinoma (HNSCC) patients, but emergence cetuximab resistance questioned its effectiveness reduced applicability. Although several possible reasons against treatment alternative therapeutic proposals have been described (EGFR alterations, activation other signaling pathways), there no method to predict anti-EGFR treatments suggest novel therapeutics. Our study investigated effect EGFR...
JAK/STAT pathway plays a well-known role in macrophage polarization, but other signaling routes may also be involved. The aim of this study was to identify new pathways and repolarize macrophages by selected protein kinase inhibitors. HL-60 derived were chosen as model cells human blood used for comparison. M1 M2 polarization HL60 promoted LPS + IFNγ (LIF) IL-4 treatments, respectively. In macrophages, mediated Erk1/2 p38 phosphorylation, while HSP27 phosphorylation involved polarization....
Abstract magnified image Valuable new synthetic intermediates, 5(6)‐(chloromethyl)benzimidazoles, were prepared by the facile elimination of sulfur dioxide under influence thionyl chloride from benzimidazole‐5(6)‐methane‐sulfonic acids easily obtained (3,4‐diaminophenyl)methanesulfonic acid with formic‐, or trifluoroacetic acid. Both reaction steps involved only acidic conditions, thus synthesis polysubstituted 5(6)‐(chloromethyl)benzimidazoles incorporating base‐sensitive substituents...
The JAK/STAT (Janus Kinase/Signal Transducer and Activator of Transcription) pathway plays a pivotal role in macrophage polarization, but other signaling routes may also be involved. aim this study was to reveal the relationship activation between rat peritoneal macrophages their detect involved, find selective protein kinase inhibitors decreasing production inflammatory proteins activated macrophages. Rat were elicited with i.p. casein injection. CD80 CD206 markers, NOS2 (Nitric oxide...
The valuable new synthetic intermediates, ethyl 4-, 6- and 7-formyl-1H-indole-2-carboxylates (10, 11, 12) were prepared from 2-ethoxycarbonyl-1H-indole-4-, 7-methanesulfonic acids (1, 2, 3), respectively. transformation of sulfomethyl group to formyl function was accomplished through elimination SO2 yield 7-chloromethyl-1H-indole-2-carboxylates (4, 5, 6), hydrolysed 7-hydroxymethyl-1H-indole-2-carboxylates (7, 8, 9), then oxidized aldehydes 12). Protection at N1 indole not necessary. A...
<div>Abstract<p>Prostate cancer remains a major cause of male mortality. Genetic alteration the PI3K/AKT/mTOR pathway is one key events in tumor development and progression prostate cancer, with inactivation PTEN suppressor being very common this type. Extensive evaluation has been performed on therapeutic potential inhibitors resistance mechanisms arising patients PTEN-mutant background. However, wild-type phenotype, have not demonstrated efficacy, an area clinical unmet need....