Comparison of Magnetic Resonance Enterography Findings and Clinical Index of the Disease Activity Score in Crohn\u27s Disease

Introduction Crohn\u27s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. It usually affects younger people, with the peak of illness between the age of 15 and 25. MR enterography (MRE) is a proven and reliable modality in the evaluation of the lesion extent within this group of patients

Human peroxisomal coenzyme A diphosphatase (NUDT7): a target enabling package (TEP)

In an effort to characterise the human NUDIX family SGC Oxford has expressed recombinant human NUDT7 as part of the SGC chemical probe programme and solved the first crystal structure of this enzyme. This enabled a crystallographic fragment screen which in conjunction with a separate covalent fragment approach yielded a first-in-class small molecule inhibitor of NUDT7 with activity in the single-digit micromolar range in a catalytic assay. This compound paves the way for chemical probe development and further functional exploration of NUDT7 in physiological and disease contexts

Unemployment as a threat to social security – the state in Poland since 2005

Unemployment is one of the most acute social issues. Th is phenomenon is complex and multidimensional, which is a threat to public safety – it brings negative consequences for the unemployed, their families and the whole society. With unemployment are related to other problems: social discontent, the load on the budget, professional deactivation, or even social marginalization. Unemployment can lead to family breakdown, or a general reduction in public health. Th erefore, the article presents the basic concepts associated with this phenomenon, but the scale of this phenomenon is shown by tests carried out on the basis of the data of the Central Statistical Offi ce and Labour Offi ces. In addition, based on the data of the Social Opinion Research Centre, examined the opinions of economically active people about their sense of threat of losing their jobs. All this is presented phenomenon of unemployment in Poland in two areas: unemployment recorded in the years 2005–2014 and the insecurity of losing current work among economically active persons in the years 2005–2015.Uznaje się, że bezrobocie jest jedną z najbardziej dotkliwych kwestii społecznych. To zjawisko złożone i wielowymiarowe, które jest zagrożeniem dla bezpieczeństwa społecznego – przynosi ujemne skutki dla bezrobotnych, ich rodzin, a także dla całego społeczeństwa. Z bezrobociem wiążą się inne problemy: niezadowolenie społeczne, obciążenie budżetu, zawodowa dezaktywacja czy nawet marginalizacja społeczna. Bezrobocie może stać się przyczyną rozpadu rodziny czy też ogólnego obniżenia zdrowotności społeczeństwa. Dlatego też w artykule przedstawiono podstawowe pojęcia związane z tym zjawiskiem, zaś jego skalę określono za pomocą badań przeprowadzonych przez Główny Urząd Statystyczny oraz Urzędy Pracy. Ponadto, w oparciu o dane Centrum Badań Opinii Społecznej, wskazano opinie osób aktywnych zawodowo na temat ich poczucia zagrożenia utratą pracy. Wszystko to zobrazowało zjawisko bezrobocia w Polsce w dwóch płaszczyznach: bezrobocie rejestrowane w latach 2005– 2014 oraz poczucie zagrożenia utratą obecnej pracy wśród osób aktywnych zawodowo w latach 2005–2015

Research data supporting '2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-one inhibitors targeting bromodomains within the Switch/Sucrose Non-Fermenting complex'.

Data in support of the characterisation of compounds and their biological binding to proteins in the above manuscript. For synthesised compounds infra-red characterisation traces, HPLC traces where performed, and processed NMR files are provided. Raw files for the interaction of key compounds with PB1(5) and SMARCA2 and SMARCA4 proteins as measured by isothermal calorimetry are included. X-ray crystallography files are available through the Protein Data Bank.This work was supported by the EPSRC [grant numbers EP/K099494/1 EP/K039520/1], Wellcome Trust [grant number 092809/Z/10/Z] and the Cambridge PhD Training Programme in Molecular Medicine

BET inhibition as a new strategy for the treatment of gastric cancer

Gastric cancer is one of the most common malignancies and a leading cause of cancer death worldwide. The prognosis of stomach cancer is generally poor as this cancer is not very sensitive to commonly used chemotherapies. Epigenetic modifications play a key role in gastric cancer and contribute to the development and progression of this malignancy. In order to explore new treatment options in this target area we have screened a library of epigenetic inhibitors against gastric cancer cell lines and identified inhibitors for the BET family of bromodomains as potent inhibitors of gastric cancer cell proliferations. Here we show that both the pan-BET inhibitor (+)-JQ1 as well as a newly developed specific isoxazole inhibitor, PNZ5, showed potent inhibition of gastric cancer cell growth. Intriguingly, we found differences in the antiproliferative response between gastric cancer cells tested derived from Brazilian patients as compared to those from Asian patients, the latter being largely resistant to BET inhibition. As BET inhibitors are entering clinical trials these findings provide the first starting point for future therapies targeting gastric cancer

Identification and Development of 2,3-Dihydropyrrolo[1,2‑<i>a</i>]quinazolin-5(1<i>H</i>)‑one Inhibitors Targeting Bromodomains within the Switch/Sucrose Nonfermenting Complex

Bromodomain containing proteins PB1, SMARCA4, and SMARCA2 are important components of SWI/SNF chromatin remodeling complexes. We identified bromodomain inhibitors that target these proteins and display unusual binding modes involving water displacement from the KAc binding site. The best compound binds the fifth bromodomain of PB1 with a <i>K</i>_D of 124 nM, SMARCA2B and SMARCA4 with <i>K</i>_D values of 262 and 417 nM, respectively, and displays excellent selectivity over bromodomains other than PB1, SMARCA2, and SMARCA4

Creation of a Novel Class of Potent and Selective MutT Homologue 1 (MTH1) Inhibitors Using Fragment-Based Screening and Structure-Based Drug Design

Recent literature has both suggested and questioned MTH1 as a novel cancer target. BAY-707 was just published as a target validation small molecule probe for assessing the effects of pharmacological inhibition of MTH1 on tumor cell survival, both <i>in vitro</i> and <i>in vivo.</i> In this report, we describe the medicinal chemistry program creating BAY-707, where fragment-based methods were used to develop a series of highly potent and selective MTH1 inhibitors. Using structure-based drug design and rational medicinal chemistry approaches, the potency was increased over 10,000 times from the fragment starting point while maintaining high ligand efficiency and drug-like properties