Search results for " inhibitors"

Abemaciclib: safety and effectiveness of a unique cyclin-dependent kinase inhibitor

2020

Introduction: The discovery and the clinical availability of novel cyclin-dependent kinases 4 and 6 inhibitors have profoundly changed the therapeutic scenario of metastatic hormone receptor-positive breast carcinoma. Among these inhibitors, abemaciclib can induce potent and sustained cell cycle arrest and immune system stimulation. Areas covered: This review summarizes the safety profile and clinical efficacy data on abemaciclib alone or in combination with aromatase inhibitors or fulvestrant in metastatic hormone receptor-positive breast carcinoma. The management of patients treated with abemaciclib is the object of this paper. Expert opinion: As shown in phase 2 and 3 clinical trials on …

Discovery of a new class of sortase a transpeptidase inhibitors to tackle gram-positive pathogens: 2-(2-phenylhydrazinylidene)alkanoic acids and rela…

2016

A FRET-based random screening assay was used to generate hit compounds as sortase A inhibitors that allowed us to identify ethyl 3-oxo-2-(2-phenylhydrazinylidene)butanoate as an example of a new class of sortase A inhibitors. Other analogues were generated by changing the ethoxycarbonyl function for a carboxy, cyano or amide group, or introducing substituents in the phenyl ring of the ester and acid derivatives. The most active derivative found was 3-oxo-2-(2-(3,4dichlorophenyl)hydrazinylidene)butanoic acid (2b), showing an IC50 value of 50 µM. For a preliminary assessment of their antivirulence properties the new derivatives were tested for their antibiofilm activity. The most active compo…

Prevalence of aphthous stomatitis in patients with inflammatory bowel disease after the treatment with monoclonal antibodies: a systematic review and…

2022

Currently, the most frequently employed therapies in the treatment of inflammatory bowel diseases (IBD), i.e., Crohn's Disease (CD), Ulcerative Colitis (UC) or unclassified IBD (IBD-U) are monoclonal anti-TNFs and anti-integrin therapies, such as vedolizumab (VDZ). Forty-seven per cent of these patients present extra-intestinal manifestations, the second most prevalent being aphthous stomatitis (AS). The present study aims to investigate which of the two therapies is associated with a lower prevalence of AS after treatment. An electronic search of the MEDLINE (via PubMed), Web of Science, SCOPUS, LILACS and OpenGrey databases was carried out. The criteria used were those described by the PR…

Consensus modelling and molecular dynamics studies for the identification of novel telomerase inhibitors as anti-cancer agents

2018

Telomerase plays an important role in early stages of life-maintaing telomere and chromosomal integrity of frequently dividing cells. It turns dormant in most somatic cells during adulthood. However, in cancer cells, telomerase gets reactivated and works tirelessly to maintain the length of telomeres, leading to immortality of cells. Hence, in this study, we have used a combined ligand-based and structure based drug design approach for the identification of novel telomerase inhibitors as anti-cancer agents. We have generated ligand-based QSAR models and structure-based pharmacophores models, according our recent MYSHAPE approach (1), and validated exhaustively. The validated models were use…

New topoisomerase I inhibitors with condensed-azaindole structure

2012

Dipeptidyl Enoates As Potent Rhodesain Inhibitors That Display a Dual Mode of Action

2015

Dipeptidyl enoates were prepared through a high-yielding two-step synthetic route. They have a dipeptidic structure with a 4-oxoenoate moiety as a warhead with multiple reactive sites. Dipeptidyl enoates were screened against rhodesain and human cathepsins B and L, and were found to be potent and selective inhibitors of rhodesain. Among them (S,E)-ethyl 5-((S)-2-{[(benzyloxy)carbonyl]amino}-3-phenylpropanamido)-7-methyl-4-oxooct-2-enoate (6) was the most potent, with an IC50 value of 16.4 nm and kinact/Ki=1.6×106 m−1 s−1 against rhodesain. These dipeptidyl enoates display a reversible mode of inhibition at very low concentrations and an irreversible mode at higher concentrations. Inhibition…

2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation

2020

2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation

New developments in the management of hepatitis C virus infection: focus on boceprevir

2012

Chronic hepatitis C virus infection is an important public health problem, and the standard treatment (combination of pegylated interferon-α and ribavirin) has an effectiveness rate of only 40%-50%. Novel virus-specific drugs have recently been designed, and multiple compounds are under development. The approval for the clinical use of direct-acting antivirals in 2011 (boceprevir [BOC] and telaprevir, viral NS3 protease inhibitors) has increased recovery rates by up to 70%. Therefore, a highly effective treatment has been envisioned for the first time. This paper focuses on BOC and the implementation of new BOC-based treatment regimes.

Mechanisms of irreversible aquaporin-10 inhibition by organogold compounds studied by combined biophysical methods and atomistic simulations

2021

Abstract The inhibition of glycerol permeation via human aquaporin-10 (hAQP10) by organometallic gold complexes has been studied by stopped-flow fluorescence spectroscopy, and its mechanism has been described using molecular modelling and atomistic simulations. The most effective hAQP10 inhibitors are cyclometalated Au(III) C^N compounds known to efficiently react with cysteine residues leading to the formation of irreversible C–S bonds. Functional assays also demonstrate the irreversibility of the binding to hAQP10 by the organometallic complexes. The obtained computational results by metadynamics show that the local arylation of Cys209 in hAQP10 by one of the gold inhibitors is mapped int…