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10.1021/jm5009902 http://scihub22266oqcxt.onion/10.1021/jm5009902 C4191604!4191604 !25211704     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25211704 &cmd=llinks): Failed to open stream: HTTP request failed! 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Identification of the first inhibitor of the GBP1:PIM1 interaction Implications for the development of a new class of anticancer agents against paclitaxel resistant cancer cells |pdf=|usr=}}{{25211704 }} gab.com Text Identification of the first inhibitor of the GBP1:PIM1 interaction Implications for the development of a new class of anticancer agents against paclitaxel resistant cancer cells JO: J Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=25211704 #FOAvip Class III ?-tubulin plays a prominent role in the development of drug resistance to paclitaxel by allowing the incorporation of the GBP1 GTPase into microtubules. Once in the cytoskeleton, GBP1 binds to prosurvival kinases such as PIM1 and initiates a signaling pathway that induces resistance to paclitaxel. Therefore, the inhibition of the GBP1:PIM1 interaction could potentially revert resistance to paclitaxel. A panel of 44 4-azapodophyllotoxin derivatives was screened in the NCI-60 cell panel. The result is that 31 are active and the comparative analysis demonstrated specific activity in paclitaxel-resistant cells. Using surface plasmon resonance, we were able to prove that NSC756093 is a potent in vitro inhibitor of the GBP1:PIM1 interaction and that this property is maintained in vivo in ovarian cancer cells resistant to paclitaxel. Through bioinformatics, molecular modeling, and mutagenesis studies, we identified the putative NSC756093 binding site at the interface between the helical and the LG domain of GBP1. According to our results by binding to this site, the NSC756093 compound is able to stabilize a conformation of GBP1 not suitable for binding to PIM1. Twit Text FOAVip Identification of the first inhibitor of the GBP1:PIM1 interaction Implications for the development of a new class of anticancer agents against paclitaxel resistant cancer cells ????J Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=25211704 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25211704 #FOAvip English Wikipedia <ref>{{Cite pmid|25211704 }}</ref> Identification of the first inhibitor of the GBP1:PIM1 interaction Implications for the development of a new class of anticancer agents against paclitaxel resistant cancer cells #MMPMID25211704 Andreoli M ; Persico M ; Kumar A ; Orteca N ; Kumar V ; Pepe A ; Mahalingam S ; Alegria AE ; Petrella L ; Sevciunaite L ; Camperchioli A ; Mariani M ; Di Dato A ; Novellino E ; Scambia G ; Malhotra SV ; Ferlini C ; Fattorusso C J Med Chem 2014[Oct]; 57 (19 ): 7916-32 PMID25211704 show ga Class III ?-tubulin plays a prominent role in the development of drug resistance to paclitaxel by allowing the incorporation of the GBP1 GTPase into microtubules. Once in the cytoskeleton, GBP1 binds to prosurvival kinases such as PIM1 and initiates a signaling pathway that induces resistance to paclitaxel. Therefore, the inhibition of the GBP1:PIM1 interaction could potentially revert resistance to paclitaxel. A panel of 44 4-azapodophyllotoxin derivatives was screened in the NCI-60 cell panel. The result is that 31 are active and the comparative analysis demonstrated specific activity in paclitaxel-resistant cells. Using surface plasmon resonance, we were able to prove that NSC756093 is a potent in vitro inhibitor of the GBP1:PIM1 interaction and that this property is maintained in vivo in ovarian cancer cells resistant to paclitaxel. Through bioinformatics, molecular modeling, and mutagenesis studies, we identified the putative NSC756093 binding site at the interface between the helical and the LG domain of GBP1. According to our results by binding to this site, the NSC756093 compound is able to stabilize a conformation of GBP1 not suitable for binding to PIM1. |Antineoplastic Agents/*chemical synthesis/pharmacology [MESH] |Binding Sites [MESH] |Cell Line, Tumor [MESH] |Computational Biology [MESH] |Drug Discovery [MESH] |Drug Resistance, Neoplasm [MESH] |GTP-Binding Proteins/*antagonists & inhibitors/chemistry [MESH] |Humans [MESH] |Models, Molecular [MESH] |Molecular Docking Simulation [MESH] |Paclitaxel/*pharmacology [MESH]Identification of the first inhibitor of the GBP1:PIM1 interaction Im(epmc).pdf DeepDyve Pubget Overpricing