Search results for "CFT"

Proton-coupled folate transporter as a biomarker of outcome to treatment for pleural mesothelioma.

2018

Caffeine boosts Ataluren's readthrough activity

2019

Abstract The readthrough of nonsense mutations by small molecules like Ataluren is considered a novel therapeutic approach to overcome the gene defect in several genetic diseases as cystic fibrosis (CF). This pharmacological approach suppresses translation termination at premature termination codons (PTCs readthrough) thus restoring the expression of a functional protein. However, readthrough might be limited by the nonsense-mediated mRNA decay (NMD), a cell process that reduces the amount/level of PTCs containing mRNAs. Here we investigate the combined action of Ataluren and caffeine to enhance the readthrough of PTCs. IB3.1 CF cells with a nonsense mutation were treated with caffeine to a…

Exploring the readthrough of nonsense mutations by non-acidic Ataluren analogues selected by ligand-based virtual screening

2016

Abstract Ataluren, also known as PTC124, is a 5-(fluorophenyl)-1,2,4-oxadiazolyl-benzoic acid suggested to suppress nonsense mutations by readthrough of premature stop codons in the mRNA. Potential interaction of PTC124 with mRNA has been recently studied by molecular dynamics simulations highlighting the importance of H-bonding and stacking π−π interactions. A series of non-acidic analogues of PTC124 were selected from a large database via a ligand-based virtual screening approach. Eight of them were synthesized and tested for their readthrough activity using the Fluc reporter harboring the UGA premature stop codon. The most active compound was further tested for suppression of the UGA non…

Multicenter validation study for the certification of a CFTR gene scanning method using next generation sequencing technology.

2018

AbstractBackground:Many European laboratories offer molecular genetic analysis of theCFTRgene using a wide range of methods to identify mutations causative of cystic fibrosis (CF) and CFTR-related disorders (CFTR-RDs). Next-generation sequencing (NGS) strategies are widely used in diagnostic practice, and CE marking is now required for most in vitro diagnostic (IVD) tests in Europe. The aim of this multicenter study, which involved three European laboratories specialized in CF molecular analysis, was to evaluate the performance of Multiplicom’s CFTR MASTR Dx kit to obtain CE-IVD certification.Methods:A total of 164 samples, previously analyzed with well-established “reference” methods for t…

Unité et scissions dans l’histoire de la CGT

2019

National audience; La question de l’unité tient une place particulière dans l’histoire de la CGT dans la mesure où elle est l’exception qui confirme la règle. En dehors des périodes 1895-1921, 1936-39 et 1943-47, la spécificité du syndicalisme confédéré réside dans sa division et son éclatement. Sur plus de 120 ans d’existence, la CGT n’a connu l’unité organique que durant une trentaine d’années (soit ¼ de son histoire). La division, ou le pluralisme si l’on préfère, est en somme la situation « normale » du syndicalisme français.Ce chapitre propose donc de comprendre les raisons et les processus qui ont conduit à cet état de dispersion ; et inversement, d’analyser les facteurs qui ont rendu…

La juridicisation de l’activité syndicale durant le Front populaire (CGT, CFTC, CSPF)

2014

National audience; Dans l’histoire du mouvement ouvrier, le Front populaire constitue un tournant puisque les syndicats tendent à s’affirmer en tant que véritables acteurs sociaux grâce à une représentativité nouvellement acquise dans le cadre d’une expérience unique d’un syndicalisme de masse. La signature des accords Matignon et les différentes dispositions juridiques qui suivent - loi sur la conciliation et l’arbitrage du 31 décembre 1936 et création de la Cour supérieure d’arbitrage en 1938 - ouvrent un chantier considérable en termes de droit du travail qui nécessite un investissement important des militants syndicaux désormais impliqués dans des procédures nouvelles (délégués-ouvriers…

Furocoumarins as multi-target agents in the treatment of cystic fibrosis.

2019

Multi-target molecular entities, offer a path to progress both in understanding causes of disease and in defining effective small molecule treatments. Coumarin and its derivatives belong to an important group of natural compounds with diverse biological properties. They are found in vegetables and plants for which literature reports thousands of publications for the great variety of biological applications among which the photoprotective effects, thus being considered multi-targeting agents. Their furan condensed analogues constitute the family of furocoumarins, less represented in the literature, endowed with photosensitizing properties and often used for the treatment of skin diseases suc…

Enhancement of premature stop codon readthrough in the CFTR gene by Ataluren (PTC124) derivatives.

2015

Abstract Premature stop codons are the result of nonsense mutations occurring within the coding sequence of a gene. These mutations lead to the synthesis of a truncated protein and are responsible for several genetic diseases. A potential pharmacological approach to treat these diseases is to promote the translational readthrough of premature stop codons by small molecules aiming to restore the full-length protein. The compound PTC124 (Ataluren) was reported to promote the readthrough of the premature UGA stop codon, although its activity was questioned. The potential interaction of PTC124 with mutated mRNA was recently suggested by molecular dynamics (MD) studies highlighting the importanc…

HETEROCYCLIC COMPOUNDS AND MEDICAL USE THEREOF

2019

The present invention relates to heterocyclic nitrogen compounds, use thereof as a medicament and pharmaceutical compositions thereof. Furthermore, the invention provides combinations of compounds of general formula (I) with therapeutic agents, such as correctors, potentiators and amplifiers of dysfunctional proteins.

Identification of a new molecule with readthrough activity to rescue CFTR protein function

In Cystic fibrosis (CF) disease nonsense mutations in the CFTR gene cause absence of the CFTR protein expression and a more severe form of the disease. About 10% of patient affected by CF show a nonsense mutation. A potential treatment of this alteration is to promote translational readthrough of premature termination codons (PTCs) by translational readthrough inducing drugs such as Ataluren. In this context we aimed to compare the 1,2,4-oxadiazole core of Ataluren with a slightly different scaffold, the 1,3,4oxadiazole core. By a validated protocol consisting of computational screening, synthesis and biological tests we identified, a new small molecule with 1,3,4-oxadiazole core (2a/NV2445…