![]() ![]() ORDER BY CAST(mt4.meta_value AS SIGNED) DESC, CAST(dxsjj_ta_value AS SIGNED) DESC, CAST(mt2.meta_value AS CHAR) ASC ) AND dxsjj_posts.post_type = 'cnio_publication' AND ((dxsjj_posts.post_status = 'publish')) ( mt4.meta_key = 'anyo' AND CAST(mt4.meta_value AS SIGNED) >= '2018' ) ( mt3.meta_key = 'id_grupos' AND mt3.meta_value LIKE '' ) PublicacionesįROM dxsjj_posts LEFT JOIN dxsjj_postmeta ON ( dxsjj_posts.ID = dxsjj_postmeta.post_id ) LEFT JOIN dxsjj_postmeta AS mt1 ON ( dxsjj_posts.ID = mt1.post_id AND mt1.meta_key = 'factor_impacto' ) LEFT JOIN dxsjj_postmeta AS mt2 ON ( dxsjj_posts.ID = mt2.post_id ) LEFT JOIN dxsjj_postmeta AS mt3 ON ( dxsjj_posts.ID = mt3.post_id ) LEFT JOIN dxsjj_postmeta AS mt4 ON ( dxsjj_posts.ID = mt4.post_id )ĭxsjj_ta_key = 'factor_impacto' ![]() These results have identified structural vulnerabilities that will make it possible to design selective RAF1 degraders. To identify such compounds, we have determined the tertiary structure of the full RAF1 protein using Cryo-Electron Microscopy (Cryo-EM) technologies. Hence, pharmacological targeting of RAF1 will require the use of strategies capable of degrading the protein. Ironically, the tumour-inducing effect of RAF1 is not mediated by its kinase activity. Ablation of this kinase induced significant levels of tumour regression with limited toxicities in experimental models. Unfortunately, all inhibitors tested thus far in the clinic have failed due to excessive toxicities. Yet patients develop drug resistance rather quickly indicating that successful treatment of KRAS mutant tumours will require combination with inhibitors of KRAS signalling pathways, such as the MAP kinase and the PI3 kinase pathways. However, selective KRAS inhibitors, at least against one of the KRAS oncogenic isoforms, KRAS G12C, have been recently approved by the FDA. For almost 4 decades, KRAS oncoproteins were thought to be undruggable targets. The main area of interest of our Group is to identify therapeutic strategies against KRAS mutant lung and pancreatic tumours. ![]()
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