A5038329456- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- MicroRNA in disease regulation
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Cancer-related gene regulation
- Cancer Genomics and Diagnostics
- Genetics and Neurodevelopmental Disorders
- Cancer-related molecular mechanisms research
- Fungal Plant Pathogen Control
- Synthesis and biological activity
- Nuclear Receptors and Signaling
- Catalytic C–H Functionalization Methods
- Asymmetric Hydrogenation and Catalysis
- Cancer, Hypoxia, and Metabolism
- Muscle metabolism and nutrition
- Multiple Myeloma Research and Treatments
- Hedgehog Signaling Pathway Studies
- HIV Research and Treatment
- Genomics and Chromatin Dynamics
- Peroxisome Proliferator-Activated Receptors
- Acute Myeloid Leukemia Research
- Bioactive Compounds and Antitumor Agents
- Family Support in Illness
- Phytochemical compounds biological activities
Sapienza University of Rome
2015-2024
Google (United States)
2018
Istituto Pasteur
2016-2017
We report the stereoselective synthesis and biological activity of a novel series tranylcypromine (TCPA) derivatives (14a-k, 15, 16), potent inhibitors KDM1A. The new compounds strongly inhibit clonogenic potential acute leukemia cell lines. In particular three molecules (14d, 14e, 14g) showing selectivity versus MAO A remarkably inhibiting colony formation in THP-1 human cells, were assessed mouse for their preliminary pharmacokinetic. 14d 14e further tested vivo murine promyelocytic model,...
Since the histone modifying enzymes EZH2 and HDACs control a number of epigenetic-dependent carcinogenic pathways, we designed first-in-class dual EZH2/HDAC inhibitor 5 displaying (sub)micromolar inhibition against both targets. When tested in several cancer cell lines, hybrid impaired viability at low micromolar level leukemia U937 rhabdomyosarcoma RH4 cells provided G1 arrest, apoptotic induction, increased differentiation, associated with an increase acetyl-H3 acetyl-α-tubulin decrease...
Glioblastoma (GBM) is the most lethal and aggressive malignant primary brain tumor in adults. After surgical resection of tumor, patient typically should be subjected to chemotherapy (temozolomide, TMZ) concomitant radiotherapy. Since TMZ treatment does not lead complete remission often develops resistance, identification efficacious therapeutics strongly pursue. Among epigenetic players, H3K27 methyltransferase (MT) EZH2 (enhancer zeste homologue 2) has been found overexpressed or mutated...
Abstract Background DNA methyltransferases (DNMTs) are epigenetic enzymes involved in embryonic development, cell differentiation, epithelial to mesenchymal transition, and control of gene expression, whose overexpression or enhanced catalytic activity has been widely reported cancer initiation progression. To date, two DNMT inhibitors (DNMTi), 5-azacytidine (5-AZA) 5-aza-2′-deoxycytidine (DAC), approved for the treatment myelodysplastic syndromes acute myeloid leukemia. Nevertheless, they...
// Evelina Miele 1, 10, * , Sergio Valente 2, Vincenzo Alfano 3 Marianna Silvano Paolo Mellini 2 Diana Borovika 4 Biagina Marrocco Agnese Po 5 Zein Mersini Besharat Giuseppina Catanzaro Giuseppe Battaglia 6 Luana Abballe Clemens Zwergel Giulia Stazi Ciro Milite 7 Sabrina Castellano 7, 8 Marco Tafani Peteris Trapencieris Antonello Mai 9 and Elisabetta Ferretti 3, 1 Center for Life NanoScience@Sapienza, Istituto Italiano di Tecnologia, Rome 00161, Italy Department of Chemistry Technologies...
The identification of new therapeutic strategies against osteosarcoma, the most common primary bone tumor, continues to be a goal improve outcomes patients refractory conventional chemotherapy. Osteosarcoma originates from transformation mesenchymal stem cells (MSC) and/or osteoblast progenitors, and loss differentiation is biological osteosarcoma feature, which has strong significance in predicting tumor aggressiveness. Thus, restoring through epigenetic reprogramming potentially...
Disruption of EZH2-embryonic ectoderm development (EED) protein-protein interaction (PPI) is a new promising cancer therapeutic strategy. We have previously reported the discovery astemizole, small-molecule inhibitor targeting EZH2-EED PPI. Herein, we report cocrystal structure EED in complex with astemizole at 2.15 Å. The elucidates detailed binding mode to and provides structure-guided design for novel inhibitor, DC-PRC2in-01, an affinity Kd 4.56 μM. DC-PRC2in-01 destabilizes PRC2 complex,...
Ligands for the bromodomain and extra-terminal domain (BET) family of bromodomains have shown promise as useful therapeutic agents treating a range cancers inflammation. Here we report that our previously developed 3,5-dimethylisoxazole-based BET ligand (OXFBD02) inhibits interactions BRD4(1) with RelA subunit NF-κB, in addition to histone H4. This shows promising profile screen NCI-60 panel but was rapidly metabolised (t
Novel pyrazole-based EZH2 inhibitors have been prepared through a molecular pruning approach from known bearing bicyclic moiety as central scaffold. The hit compound 1o ( N -((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-methyl-1-phenyl-1 H -pyrazole-4-carboxamide) showed low micromolar EZH2/PRC2 inhibition and high selectivity towards panel of other methyltransferases. Moreover, displayed cell growth arrest in breast MDA-MB231, leukaemia K562, neuroblastoma SK-N-BE cancer cells...
DNA methyltransferases (DNMTs) play a relevant role in epigenetic control of cancer cell survival and proliferation. Since only two DNMT inhibitors (azacitidine decitabine) have been approved to date for the treatment hematological malignancies, development novel potent specific is urgent. Here we describe design, synthesis, biological evaluation new series compounds acting at same time as DNMTs (mainly DNMT3A) degraders. Tested against leukemic solid lines, 2a–c 4a–c (the last leukemias)...