A5078355464- Genetics and Neurodevelopmental Disorders
- Epilepsy research and treatment
- Down syndrome and intellectual disability research
- Lung Cancer Research Studies
- Neuroscience and Neuropharmacology Research
- Cancer therapeutics and mechanisms
- Signaling Pathways in Disease
- Ion Transport and Channel Regulation
- Autism Spectrum Disorder Research
- Advanced Chemical Sensor Technologies
- Sphingolipid Metabolism and Signaling
- Synthesis and Catalytic Reactions
- Olfactory and Sensory Function Studies
- Neurogenesis and neuroplasticity mechanisms
- Synthesis and biological activity
- Protein Degradation and Inhibitors
- Bioactive Compounds and Antitumor Agents
- Salivary Gland Disorders and Functions
- Neutropenia and Cancer Infections
Italian Institute of Technology
2017-2021
Aberrant expression ratio of Cl− transporters, NKCC1 and KCC2, is implicated in several brain conditions. inhibition by the FDA-approved diuretic drug, bumetanide, rescues core symptoms rodent models and/or clinical trials with patients. However, bumetanide has a strong effect due to kidney transporter NKCC2, creating critical drug compliance issues health concerns. Here, we report discovery new chemical class selective inhibitors lead candidate ARN23746. ARN23746 restores physiological...
Alterations in the expression of Cl
We used a pharmacophore hybridization strategy to combine key structural elements of merbarone and etoposide generated new type II topoisomerase (topoII) poisons. This first set hybrid topoII poisons shows promising antiproliferative activity on human cancer cells, endorsing their further exploration for anticancer drug discovery.
We disclose a novel class of 6-amino-tetrahydroquinazoline derivatives that inhibit human topoisomerase II (topoII), validated target anticancer drugs. In contrast to topoII-targeted drugs currently in clinical use, these compounds do not act as topoII poisons enhance enzyme-mediated DNA cleavage, mechanism is linked the development secondary leukemias. Instead, tetrahydroquinazolines block function with no evidence intercalation. identified potent lead compound [compound 14 (ARN-21934) IC50...
Intracellular chloride concentration [Cl–]i is defective in several neurological disorders. In neurons, mainly regulated by the action of Na+–K+–Cl– importer NKCC1 and K+–Cl– exporter KCC2. Recently, we have reported discovery ARN23746 as lead candidate a novel class selective inhibitors NKCC1. Importantly, able to rescue core symptoms Down syndrome (DS) autism mouse models. Here, describe extensive characterization this chemical inhibitors, with focus on other promising derivatives....
Acid ceramidase (AC) hydrolyzes ceramides, which are central lipid messengers for metabolism and signaling of sphingolipids. A growing body evidence links deregulation sphingolipids to several diseases, including cancer. Indeed, AC expression is abnormally high in melanoma cells. inhibition may thus be key treating malignant melanoma. Here, we have used a systematic scaffold exploration design general pharmacophore inhibition. This comprises 6 + 5 fused ring heterocycle linked an aliphatic...
<h3>Objective:</h3> The aim of this work was to search for selective NKCC1 inhibitors devoid undesired diuretic effects as a sustainable therapeutic solution brain disorders characterized by defective NKCC1/KCC2 expression-ratio. <h3>Background:</h3> Proper intracellular chloride concentration is fundamental physiological development and function. Accordingly, the aberrant expression-ratio chloride-importer -exporter KCC2 implicated in several conditions, including drug-resistant epilepsy...