showing 5 related works from this author
Controlled Iontophoretic Delivery in Vitro and in Vivo of ARN14140—A Multitarget Compound for Alzheimer’s Disease
2019
ARN14140 is a galantamine-memantine conjugate that acts upon both cholinergic and glutamatergic pathways for better management of Alzheimer's disease. Poor oral bioavailability and pharmacokinetics meant that earlier preclinical in vivo studies employed intracerebroventricular injection to administer ARN14140 directly to the brain. The aim of the present study was to evaluate the feasibility of using constant current transdermal iontophoresis for the noninvasive systemic delivery of ARN14140 and to quantify the amounts present in the blood and the brain. Preliminary experiments in vitro were performed using porcine skin and validated with human skin. Cumulative ARN14140 permeation across th…
STAT1 and Its Crucial Role in the Control of Viral Infections
2022
The signal transducer and activator of transcription (STAT) 1 protein plays a key role in the immune response against viruses and other pathogens by transducing, in the nucleus, the signal from type I, type II and type III IFNs. STAT1 activates the transcription of hundreds of genes, some of which have been well characterized for their antiviral properties. STAT1 gene deletion in mice and complete STAT1 deficiency in humans both cause rapid death from severe infections. STAT1 plays a key role in the immunoglobulin class-switch recombination through the upregulation of T-bet; it also plays a key role in the production of T-bet+ memory B cells that contribute to tissue-resident humoral memory…
GPCR Inhibition in Treating Lymphoma
2022
G protein-coupled receptors (GPCRs) are important classes of cell surface receptors involved in multiple physiological functions. Aberrant expression, upregulation, and mutation of GPCR signaling pathways are frequent in many types of cancers, promoting hyperproliferation, angiogenesis, and metastasis. Recent studies showed that alterations of GPCRs are involved in different lymphoma types. Herein, we review the synthetic strategies to obtain GPCR inhibitors, focusing on CXCR4 inhibitors which represent most of the GPCR inhibitors available in the market or under preclinical investigations for these diseases.
Targeting the JAK/STAT Pathway: A Combined Ligand- and Target-Based Approach
2021
Janus kinases (JAKs) are a family of proinflammatory enzymes able to mediate the immune responses and the inflammatory cascade by modulating multiple cytokine expressions as well as various growth factors. In the present study, the inhibition of the JAK-signal transducer and activator of transcription (STAT) signaling pathway is explored as a potential strategy for treating autoimmune and inflammatory disorders. A computationally driven approach aimed at identifying novel JAK inhibitors based on molecular topology, docking, and molecular dynamics simulations was carried out. For the best candidates selected, the inhibitory activity against JAK2 was evaluated in vitro. Two hit compounds with…
Antiproliferative agents that interfere with the cell cycle at the G(1)-->S transition: further development and characterization of a small library o…
2008
In this continuation of our research on derivatives containing the stilbene privileged structure or that are derived from it, we report the results of further studies carried out on the previously initiated collection of compounds. We used a parallel synthetic approach to rapidly obtain small sets of compounds and started the annotation of the library in progress by calculating some physicochemical properties to be eventually correlated with biological activities. A pharmacophore for the antiproliferative activity was also built to summarize the features of the library. We evaluated the antiproliferative and pro-apoptotic activities of all compounds as well as the cell-cycle effects of some…