345 research outputs found
Benzothiadiazole derivatives endowed with STAT3 inhibition
No full textBENZOTHIADIAZOLE DERIVATIVES ENDOWED WITH STAT3
INHIBITION
Arianna Gelain (1), Matteo Mori (1), Ettore Gilardoni (1), Luca Regazzoni (1), Alessandro Pedretti (1),
Diego Colombo (2), Gary Parkinson (3), Akira Asai (4), Fiorella Meneghetti (1), Stefania Villa (1)
1) Department of Pharmaceutical Sciences, University of Milan, via L. Mangiagalli 25, 20133 Milan, Italy
2) Department of Medical Biotechnology and Translational Medicine, University of Milan, via C. Saldini 50, 20133 Milan,
Italy
3) Department of Pharmaceutical and Biological Chemistry – UCL School of Pharmacy, University College London, 29/39
Brunswick Square, WC1N 1AX London, United Kingdom
4) Center for Drug Discovery – Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku,
422-8526 Shizuoka, Japan
Signal Transducer and Activator of Transcription 3 (STAT3) is a latent cytoplasmic protein over-expressed in
various cancer cell lines1,2. As a part of our ongoing research focused on compounds showing STAT3 SH2
domain inhibiting activity3,4, by a virtual screening approach, we identified 5,6-dimethyl-1H,3H
-2,1,3-benzothiadiazole-2,2-dioxide (1) as potential inhibitor. Several derivatives were synthesized (Figure 1)
and tested. Since compound 1 exhibited the most interesting activity (IC50 = 15.8 ± 0.6 μM by
AlphaScreen-based assay), we decided to investigate the mechanism of its activity by liquid chromatography,
MS and UV studies, discovering compound 1 unexpected interaction also with cysteine residues5.
Figure 1 . Benzothiadiazole-2,2-dioxide derivatives set
References
1) Darnell, J. Jr Science, 1997, 277, 1630-1635
2) Turkson, J. and Jove R. Oncogene, 2000, 19, 6613-6626
3) Meneghetti, F.; Villa, S.; Masciocchi, D.; Barlocco, D.; Toma, L.; Han, D.C.; Kwon, B.M.; Ogo, N.; Asai, A.; Legnani, L.;
Gelain, A. European J. Org. Chem. 2015, 2015, 4907–4912
4) Porta, F.; Facchetti, G.; Ferri, N.; Gelain, A.; Meneghetti, F.; Villa, S.; Barlocco, D.; Masciocchi, D.; Asai, A.; Miyoshi,
N.; Marchianò, S.; Kwon, B.M.; Jin, Y.; Gandin, V.; Marzano, C.; Rimoldi, Eur. J. Med. Chem. 2017, 131, 196–206
5) Mori, M.; Gilardoni, E.; Regazzoni, L.; Pedretti, A.; Colombo, D.; Parkinson, G.; Asai, A,; Meneghetti, F.; Villa, S.;
Gelain, A., Molecules 2020, 25(15), 3509
A Distributed Extended Kalman Filtering network for estimation and tracking of multiple objects
No full textThe author presents a strategy for tracking areas occupied by many objects moving in a scene and monitored by means of image sequences. The proposed strategy can be used to solve the problems of crowding estimation and localisation of groups of people in underground stations
Methodology integration along the product development process: a case study
No full textThe growing complexity of the market, customer demands for increasing quality and service, together with the need of lower prices and more timely delivery challenge companies to improve performance on every aspect of their products and processes. Continuous advances in Information Technology (IT) allow companies to understand and exploit the changes of this fast-moving environment, providing the capabilities to efficiently support the company’s product lifecycle. In fact the management of product development in a whole-life-comprehensive perspective focuses on the fragmentation of existing tools and processes with the aim of gathering a fluid flow, an efficient definition and a ready use of product information throughout the organization. In such a context a Product Lifecycle Management (PLM) system can provide a valid support for the coordination and integration of processes and applications used to define and manage the virtual product with those used to manufacture and maintain the real product. As said, a PLM system/process is supported by several IT elements that can be grouped into three main categories: Product definition, Planning and Control and Infrastructure. In this paper the attention is put on methodologies and tools for product definition, and in particular, on the integration between traditional ones and those devoted to systematic innovation since they are assuming more and more importance in order to make companies able to innovate their products and processes.Thus, the aim of this work is to illustrate methodologies and tools involving several aspects of products and processes in a product lifecycle management context. In particular among the methodologies that can be adopted to support conceptual design and management of product variants, TRIZ methodology has been fruitfully employed, together with other tools (such as Design for Modularity, Lean Manufacturing or Risk Management) to create a new paradigm of product development. A step by step roadmap has been created to guide technicians along some of the phases of product life cycle in order to decrease time to market of customized products paying attention to cost and increasing quality standards
El carácter elusivo de la historia en la "Guerra del fin del mundo" de Mario Vargas Llosa
No full textRoma, Bulzon
A real-time model-based method for 3-D object orientation estimation in outdoor scenes
No full textThis letter presents a new method for real-time determination of the three-dimensional (3-D) orientation, i.e., the rotation angle with respect to one of the principal object axes, of a moving known object from a monocular image sequence, The method is composed by three steps: 1) extraction of the morphological skeleton from binary images, 2) projection of the skeleton function on two planes and its analytical approximation by nonuniform rational B-splines, and 3) comparison with a set of data stored into a model. database, Several experiments per-formed on real images prove the method's validity
Il problema della penale «irrisoria» nella prospettiva delle clausole di esonero da responsabilità
No full textIl commento esamina criticamente gli orientamenti in merito al sindacato giudiziale sulle clausole penali di ammontare «irrisorio», individuandone il fondamento (anche in esito ad un confronto con l’ordinamento francese) in un’applicazione diretta alla clausola penale dell’art. 1229 c.c., qualora l’importo pattuito risulti notevolmente inferiore all’entità del danno prevedibile. Si analizzano inoltre gli effetti che la previsione di nullità ex art. 1229 può sortire in questa fattispecie, con lo scopo di salvaguardare le utilità derivanti dalla penale in favore del creditore.The author critically examines the various theses about the judicial review of an «extremely modest» penalty clause. After a comparison with the French legal system, the author argues that such review is allowed by the direct application of Art. 1229 of the Civil Code to the penalty clause, where the agreed amount is significantly lower than the foreseeable damage. Furthermore, an analysis is drawn of the effects that the provision of nullity under Art. 1229 may have in such a case, with the aim of maintaining the benefits granted by the penalty to the creditor
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