A5059757863- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Computational Drug Discovery Methods
- Cholinesterase and Neurodegenerative Diseases
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Synthesis and Catalytic Reactions
- Nicotinic Acetylcholine Receptors Study
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Alzheimer's disease research and treatments
- Multiple Myeloma Research and Treatments
- Protein Structure and Dynamics
- Eicosanoids and Hypertension Pharmacology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Adenosine and Purinergic Signaling
- Field-Flow Fractionation Techniques
- Chemical Synthesis and Analysis
- Heat shock proteins research
- Analytical Chemistry and Sensors
- Steroid Chemistry and Biochemistry
- Chromatin Remodeling and Cancer
- Molecular Sensors and Ion Detection
University of Salerno
2015-2024
NanoTemper Technologies (Germany)
2017
Istituto Nazionale di Fisica Nucleare, Gruppo Collegato di Salerno
1998
Several findings propose the altered tau protein network as an important target for Alzheimer's disease (AD). Particularly, two points of pharmacological intervention can be envisaged: inhibition phosphorylating kinase GSK-3β and aggregation process. On basis this consideration on our interest in multitarget paradigms AD, we report discovery 2,4-thiazolidinedione derivatives endowed with such a profile. 28 30 displayed micromolar IC50 values toward GSK-3β, together capacity inhibiting AcPHF6...
In a high percentage (≥85%) of both sporadic and familial adenomatous polyposis forms colorectal cancer (CRC), the inactivation APC tumor suppressor gene initiates formation modulates Wnt/β-Catenin transduction pathways involved in control cell proliferation, adhesion metastasis. Increasing evidence showed that endocannabinoids growth progression, vitro vivo. We evaluated effect Rimonabant, Cannabinoid Receptor 1 (CB1) inverse agonist, on pathway HCT116 SW48 lines carrying genetic profile...
Selective inhibitors of the two paralogue KAT3 acetyltransferases (CBP and p300) may serve not only as precious chemical tools to investigate role these enzymes in physiopathological mechanisms but also lead structures for development further antitumor agents. After application a molecular pruning approach hardly optimizable very cell-permeable garcinol core structure, we prepared many analogues that were screened their inhibitory effects using biochemical biophysical (SPR) assays. Further...
Since the discovery of compound BIX01294 over 10 years ago, only a very limited number nonquinazoline inhibitors H3K9-specific methyltransferases G9a and G9a-like protein (GLP) have been reported. Herein, we report identification novel chemotype for G9a/GLP inhibitors, based on underinvestigated 2-alkyl-5-amino- 2-aryl-5-amino-substituted 3H-benzo[e][1,4]diazepine scaffold. Our research efforts resulted in 12a (EML741), which not maintained high vitro cellular potency its quinazoline...
Protein arginine methyltransferases (PRMTs) are important therapeutic targets, playing a crucial role in the regulation of many cellular processes and being linked to diseases. Yet, there is still much be understood regarding their functions biological pathways which they involved, as well on structural requirements that could drive development selective modulators PRMT activity. Here we report deconstruction-reconstruction approach that, starting from series type I inhibitors previously...
Inhibition of Carbonic Anhydrases (CAs) has been clinically exploited for many decades a variety therapeutic applications. Within research project aimed at developing novel classes CA inhibitors (CAIs) with proper selectivity certain isoforms, series derivatives featuring the 2-substituted-benzimidazole-6-sulfonamide scaffold, conceived as frozen analogs Schiff bases and secondary amines previously reported in literature CAIs, were investigated. Enzyme inhibition assays on physiologically...
KAT8 is a lysine acetyltransferase primarily catalyzing the acetylation of Lys16 histone H4 (H4K16). dysregulation linked to development and metastatization many cancer types, including non-small cell lung (NSCLC) acute myeloid leukemia (AML). Few inhibitors have been reported so far, none which displaying selective activity. Based on KAT3B/KDAC inhibitor C646, we developed series N-phenyl-5-pyrazolone derivatives identified compounds 19 34 as low-micromolar over panel KATs KDACs. Western...
SIRT1, a NAD+-dependent deacetylase, is the most well-studied member of class III histone deacetylases. Due to its wide range activities and substrate targets, this enzyme has emerged as major regulator different physiological processes. However, SIRT1-mediated alterations are also implicated in pathogenesis several conditions, including metabolic neurodegenerative disorders, cancer. Current evidence highlights potential role SIRT1 an attractive therapeutic target for disease prevention...
Less studied than the other protein arginine methyltransferase isoforms, PRMT7 and PRMT9 have recently been identified as important therapeutic targets. Yet, most of their biological roles functions are still to be defined, well structural requirements that could drive identification selective modulators activity. We described led potent PRMT4 inhibitors spanning both substrate cosubstrate pockets. The reanalysis data suggested a preferential binding for shorter derivatives prompted us...
Being the standard solvent for preparing stock solutions of compounds drug discovery, DMSO is always present in assay buffers concentrations ranging from 0.1 % to 5 (v/v). Even at lowest concentrations, DMSO-containing can have significant effects on individual proteins and possible pitfalls cannot be eliminated. Herein, we used two protein systems, lysine methyltransferases G9a/KMT1 C SETD8/KMT5 A, study stability binding corresponding inhibitors, using different biophysical methods such as...
Aim: Alzheimer's disease is a still untreatable multifaceted pathology, and drugs able to stop or reverse its progression are urgently needed. In this picture, the recent reformulation of cholinergic hypothesis renewed interest for acetylcholinesterase inhibitors. paper, series naturally inspired chalcone-based carbamates was designed target cholinesterase enzymes possibly generate fragments endowed with neuroprotective activity in situ. Results & methodology: All compounds presented study...
Abstract Dysregulation of the activity lysine acetyltransferases (KATs) is related to a variety diseases and/or pathological cellular states; however, their role remains unclear. Therefore, development selective modulators these enzymes paramount importance, because molecules could be invaluable tools for assessing importance KATs in several pathologies. We recently found that diethyl pentadecylidenemalonate (SPV106) possesses previously unobserved inhibitor/activator profile against protein...
Protein arginine methyltransferase (PRMT) 4 (also known as coactivator-associated 1; CARM1) is involved in a variety of biological processes and considered an emerging target class oncology other diseases. A successful strategy to identify PRMT substrate-competitive inhibitors has been exploit chemical scaffolds able mimic the substrate. (S)-Alanine amide moiety valuable for development potent selective PRMT4 inhibitors; however, its high hydrophilicity led derivatives with poor cellular...
The bromodomain and extra-terminal (BET) family of proteins includes BRD2, BRD3, BRD4, the testis-specific protein, BRDT, each containing two N-terminal tandem (BRD) modules. Potent selective inhibitors targeting bromodomains are required to elucidate their biological role(s), with potential clinical applications. In this study, we designed synthesized a series benzimidazole-6-sulfonamides starting from azobenzene compounds MS436 (7 a) MS611 b) that exhibited preference for first (BD1) over...
// Francesca Petraglia 1, * , Abhishek A. Singh 2, Vincenzo Carafa Angela Nebbioso 1 Mariarosaria Conte 3 Lucia Scisciola Sergio Valente 4 Alfonso Baldi 5 Amit Mandoli 2 Valeria Belsito Petrizzi 6 Concetta Ingenito Sandro De Falco 7 Cicatiello Ivana Apicella Eva M. Janssen-Megens Bowon Kim Guoqiang Yi Colin Logie Simon Heath 8 Menotti Ruvo 9 Albertus T.J. Wierenga 10 Paul Flicek 11 Marie Laure Yaspo 12 Veronique Della Valle 13 Olivier Bernard Stefano Tomassi 14 Ettore Novellino Alessandra...
<h2>Abstract</h2> MRG15 is a transcription factor containing the methyl-lysine reader chromodomain. Despite its involvement in different physiological and pathological states, to date role of this protein has not been fully elucidated due lack specific potent chemical probe. In work, we report development microscale thermophoresis (MST)-based assay for study MRG15–ligand binding interactions. After development, was validated using small focused library UNC1215 as reference compound, yield...