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[EN] The invention relates to a compound having formula (I) or a stereoisomer, a salt or a solvate, in which: A is -CH(OH)- or -C(=0)-; Z is H or OH; n is 0 or 1; R1 is alkyl(C1-C30), alkenyl(C2-C30) or alkynyl(C2-C30); B is -H, -N3 or -C?CH; R2 is -NHR3 or maleimide; R3 is -COR4, -COCOR4 or -SO2R4; and R4 is alkyl(C1-C16), alkenyl(C2-C16), alkynyl(C2-C16), epoxide or aziridine, on the condition that: a) when A is -CH(OH) and B is H, R3 is different from -COR4, R4 being alkyl(C1-C16); b) when A is -CH(OH), B is H and R3 is -COCOR4,R4 beingalkyl(C6), R1 is different from -CH=CH2-alkyl(C12), -C?CH-alkyl(C12) or alkyl(C13-C15); or c) when A is -C(=O), R1 is alkenyl(C2-C30), B is H and n is 0, R3 is different from -COR4, R4 being alkyl(C1C16). The invention also relates to the use of the compound having formula (I), 2,2-dibromo-N-((2S,3R)-1,3-dihydroxyoctadecan-2-il)acetamide or 2-bromo-N-((2S,3R)-1,3-dihydroxyoctadecan-2-il)acetamide in the treatment or prevention of a disease associated with cellular hyperproliferation, either alone or in combination., Consejo Superior de Investigaciones Científicas (España), Universidad de Barcelona (España), A1 Solicitud de patente con informe sobre el estado de la técnica

Fecha de solicitud: 04-02-2009.- Titular: Consejo Superior de Investigaciones Científicas (CSIC), The invention relates to a compound R-(CR 1 R 2 )q-CO-N(R 3 )-C(R 4< /sub>R 5 )-CO-NH 2 (I), wherein: R is a heterocyclyl radical; R 1 and R 2 independently represent H or alkyl; R 3 is H, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl; R 4 and R 5 independently represent H or alkyl; q is a number between 0 and 1; and the salts, solvates, pro-drugs or stereoisomers thereof, which can inhibit UBC13-UEV interactions and be used in the production of pharmaceutical compositions intended for antitumour therapy or the treatment and/or prophylaxis of diseases associated with metabolic routes involving the UBC13 enzyme, metabolic routes involving transcriptional factor NF-kappaB or routes involving PCNA or RAD6., La invención relaciona a un r del compuesto (CR 1 R 2) q-CO-n (R 3) - C (R 4< /sub> R 5) - CO-NH 2 (i), en donde: R es un heterociclil radical R 1 y R 2 representan independientemente H o el alquílico R 3 es H, alquílico, cicloalquil, cicloalquilalquilo, alquenil, arílico, arilalquilo, heterociclil o heterocyclylalkyl R 4 y R 5 representan independientemente H o el alquílico q es un número entre 0 y 1 y las sales, los solvates, los pro-drugs o los stereoisomers de eso, que el bote inhibe interacciones de UBC13-UEV y sea utilizado en la producción de composiciones farmacéuticas destinadas para la terapia antitumour o el tratamiento y/o la profilaxis de las enfermedades asociadas con las vías metabólicas que implican la enzima UBC13, las vías metabólicas que implican el factor transcripcional N-F-kappaB o las vías que implican PCNA o RAD6.

Modelos celulares de cáncer de próstata. Líneas celulares, PC-3/S-luc y PC-3/M-luc, derivadas de la línea de cáncer de próstata PC-3, modificadas de forma que expresan el gen luciferasa (luc) para el desarrollo de un modelo de cáncer, útil para el diagnóstico y/o pronóstico de cáncer, específicamente de próstata, determinando la diferente expresión génica de los marcadores biológicos de invasividad y metástasis. Así como, un método in vitro de búsqueda de agentes para tratamiento o prevención del cáncer., Consejo Superior de Investigaciones Científicas (España), A1 Solicitud de patente con informe sobre el estado de la técnica

Fecha de solicitud: Titulares: Consejo Superior de Investigaciones Científicas (CSIC).- Hospital Vall d´Hebron .- Reventos Puigjaner., [EN]The invention relates to the tissue-type plasminogen activator (t-PA) which is a serine protease that is overexpressed in various different types of tumours, including cancer of the pancreas, melanomas and neuroblastomas. More specifically, the invention relates to t-PA activity and expression inhibitors that have been developed as antitumour agents. [ES]El activador tisular del plasminógeno (t-PA) es una serina proteasa sobreexpresada en varios tipos de tumores, incluyendo cáncer de páncreas, melanomas y neuroblastomas. En la presente invención han sido desarrollados inhibidores de la expresión y actividad del t-PA como agentes antitumorales.

Fecha de solicitud:14.03.2002.- Titulares:Consejo Superior de Investigaciones Científicas (CSIC).-Hospital Vall D´Hebron., [EN] The invention relates to a novel overexpressed gene and protein in prostate cancer that has been identified and sequenced and the invention demonstrates that said protein is overexpressed in prostate adenocarcinoma using the western-blot and RT-PCR technique. The expression of said protein is correlated with the proliferation of tumours. Specific antibodies have been generated that specifically detect the protein both in cell lines and in human normal and tumour tissue using immunological methods. Using said antibodies, the invention demonstrates that the protein is overexpressed in the majority of human prostate adenocarcinomas and, therefore, the detection of said transcript and protein constitutes a novel marker for this type of tumour, with potential use in the diagnosis thereof. Furthermore, said protein is a target protein. The invention also relates to the identification of compounds for antitumour therapies.[ES]Un nuevo gen y proteína sobreexpresado en cáncer de próstata ha sido identificado y secuenciado. En la presente invención se demuestra que se sobreexpresa en adenocarcinoma de próstata mediante la técnica RT-PCR y western-blot. La expresión de esta proteína está correlacionada con la proliferación de tumores. Han sido generados anticuerpos específicos que detectan específicamente la proteína tanto en líneas celulares como en tejidos humanos normales y tumorales usando métodos inmunológicos. Empleando estos anticuerpos, demostramos que la proteína se sobreexpresa en la mayoría de los adenocarcinomas de próstata humanos, por lo que la detección de este tránscrito y proteína constituye un nuevo marcador de este tipo de tumores, con potencial utilidad en su diagnóstico. Esta proteína es además una proteína diana la identificación de compuestos para terapias antitumorales.

The “one-gene, one-protein” rule, coined by Beadle and Tatum, has been fundamental to molecular biology. The rule implies that the genetic complexity of an organism depends essentially on its gene number. The discovery, however, that alternative gene splicing and transcription are widespread phenomena dramatically altered our understanding of the genetic complexity of higher eukaryotic organisms; in these, a limited number of genes may potentially encode a much larger number of proteins. Here we investigate yet another phenomenon that may contribute to generate additional protein diversity. Indeed, by relying on both computational and experimental analysis, we estimate that at least 4%–5% of the tandem gene pairs in the human genome can be eventually transcribed into a single RNA sequence encoding a putative chimeric protein. While the functional significance of most of these chimeric transcripts remains to be determined, we provide strong evidence that this phenomenon does not correspond to mere technical artifacts and that it is a common mechanism with the potential of generating hundreds of additional proteins in the human genome.

Epithelial-mesenchymal-transition promotes intra-tumoral heterogeneity, by enhancing tumor cell invasiveness and promoting drug resistance. We integrated transcriptomic data for two clonal subpopulations from a prostate cancer cell line (PC-3) into a genome-scale metabolic network model to explore their metabolic differences and potential vulnerabilities. In this dual cell model, PC-3/S cells express Epithelial-mesenchymal-transition markers and display high invasiveness and low metastatic potential, while PC-3/M cells present the opposite phenotype and higher proliferative rate. Model-driven analysis and experimental validations unveiled a marked metabolic reprogramming in long-chain fatty acids metabolism. While PC-3/M cells showed an enhanced entry of long-chain fatty acids into the mitochondria, PC-3/S cells used long-chain fatty acids as precursors of eicosanoid metabolism. We suggest that this metabolic reprogramming endows PC-3/M cells with augmented energy metabolism for fast proliferation and PC-3/S cells with increased eicosanoid production impacting angiogenesis, cell adhesion and invasion. PC-3/S metabolism also promotes the accumulation of docosahexaenoic acid, a long-chain fatty acid with antiproliferative effects. The potential therapeutic significance of our model was supported by a differential sensitivity of PC-3/M cells to etomoxir, an inhibitor of long-chain fatty acid transport to the mitochondria.

Endothelial Cells (ECs) dysfunctionality and pathological blood vessel responses are associated with metabolic alterations and can be considered a primary factor in the onset and progression of atherosclerosis [1] and other vascular related diseases, such as acute myocardial infarction. This disease is a leading cause of morbidity worldwide and occurs when myocardial ischemia exceeds a critical threshold and overcomes myocardial cellular repair mechanisms designed to maintain normal function and homeostasis. Preliminary data from our group have suggested that ECs derived from acute myocardial infarction patients show an altered phenotype with lower proliferation and contribute to neovascularization. In this study we aim to establish an in vitro model of endothelial pathology [2] using patient-derived endothelial cell lines which are subjected to a systematic evaluation against control cells, to determine the metabolic profile and deep investigate if the endothelial dysfunctionality is a consequence of an abnormal endothelial cell metabolism. The recent results obtained are a part of this attempt, and include a preliminary study of cells growth and of its ability in migration. This study also aims at performing a complete characterization of the metabolic profiles of ECs in normal and pathological conditions, and will include an integrated systems biology approach and proteomic analysis. The identification of novel therapeutic targets to enhance endothelial function and prevent acute coronary syndrome is one of the principal objectives of our research. This work was supported by funds of European Union’s Horizon MOGLYNET (grant agreement nº 6755279); AGAUR – Generalitat de Catalunya (2014SGR1017); M.C. acknowledges the support received through “ICREA Academia” (ICREA foundation – Generalitat de Catalunya). References [1] J.Goveia, P.Stapor, P.Carmeliet “Principles of targeting endothelial cell metabolism to treat angiogenesis and endothelial cell dysfunction in disease” EMBO Molecular Medicine. 2014; 6(9):1105-20 [2] Mills NL, Tura O, Padfield GJ, Millar C, Lang NN, Stirling D, Ludlam C, Turner ML, Barclay GR, Newby DE. “Dissociation of phenotypic and functional endothelial progenitor cells in patients undergoing percutaneous coronary intervention.” Heart, 2009; 95(24):2003-8

Atherosclerosis is a disease associated with premature biological aging, [1] as atherosclerotic plaques show evidence of cellular senescence. Emerging evidences indicate that pathological blood vessel responses and dysfunctionality of Endothelial Cells (ECs) are associated with metabolic alterations and can be considered a primary factor in the onset and progression of atherosclerosis and other vascular related diseases, such as acute myocardial infarction. This is a leading cause of morbidity worldwide and occurs when myocardial ischemia exceeds a critical threshold and overcomes myocardial cellular repair mechanisms designed to maintain normal function and homeostasis. Preliminary data from our group have suggested that ECs derived from acute myocardial infarction patients show an altered phenotype with lower proliferation and contribute to neovascularization. In this study we aim to establish an in vitro model of endothelial pathology using patient-derived endothelial cell lines which are subjected to a systematic evaluation against control cells, [2] to determine the metabolic profile and deep investigate if the endothelial dysfunctionality is a consequence of an abnormal endothelial cell metabolism. The recent results obtained are a part of this attempt, and include a preliminary study of cells growth and of its ability in migration. This study also aims at performing a complete characterization of the metabolic profiles of ECs in normal and pathological conditions, and will include an integrated systems biology approach and proteomic analysis. The identification of novel therapeutic targets to enhance endothelial function and prevent acute myocardial syndrome is one of the principal objectives of our research. [1] J.Goveia, P.Stapor, P.Carmeliet “Principles of targeting endothelial cell metabolism to treat angiogenesis and endothelial cell dysfunction in disease” EMBO Molecular Medicine. 2014; 6(9):1105-20 [2] Mills NL, Tura O, Padfield GJ, Millar C, Lang NN, Stirling D, Ludlam C, Turner ML, Barclay GR, Newby DE. “Dissociation of phenotypic and functional endothelial progenitor cells in patients undergoing percutaneous coronary intervention.” Heart, 2009; 95(24):2003-8 This work was supported by funds of European Union’s Horizon MOGLYNET (grant agreement nº 6755279); AGAUR – Generalitat de Catalunya (2014SGR1017); M.C. acknowledges the support received through “ICREA Academia” (ICREA foundation – Generalitat de Catalunya).