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10.1158/1535-7163.MCT-15-0511 http://scihub22266oqcxt.onion/10.1158/1535-7163.MCT-15-0511 C4636458!4636458 !26358752     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26358752 &cmd=llinks): Failed to open stream: HTTP request failed! 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Identification of Novel Ezrin Inhibitors Targeting Metastatic Osteosarcoma by Screening Open Access Malaria Box |pdf=|usr=}}{{26358752 }} gab.com Text Identification of Novel Ezrin Inhibitors Targeting Metastatic Osteosarcoma by Screening Open Access Malaria Box JO: Mol Cancer Ther http://www.kidney.de/pget.php?&tw=1&pmid=26358752 #FOAvip Ezrin is a member of the ERM (ezrin, radixin, moesin) family of proteins and functions as a linker between the plasma membrane and the actin cytoskeleton. Ezrin is a key driver of tumor progression and metastatic spread of osteosarcoma. We discovered a quinoline-based small molecule, NSC305787, that directly binds to ezrin and inhibits its functions in promoting invasive phenotype. NSC305787 possesses a very close structural similarity to commonly used quinoline-containing antimalarial drugs. On the basis of this similarity and of recent findings that ezrin has a likely role in the pathogenesis of malaria infection, we screened antimalarial compounds in an attempt to identify novel ezrin inhibitors with better efficacy and drug properties. Screening of Medicines for Malaria Venture (MMV) Malaria Box compounds for their ability to bind to recombinant ezrin protein yielded 12 primary hits with high selective binding activity. The specificity of the hits on ezrin function was confirmed by inhibition of the ezrin-mediated cell motility of osteosarcoma cells. Compounds were further tested for phenocopying the morphologic defects associated with ezrin suppression in zebrafish embryos as well as for inhibiting the lung metastasis of high ezrin-expressing osteosarcoma cells. The compound MMV667492 exhibited potent anti-ezrin activity in all biologic assays and had better physicochemical properties for drug-likeness than NSC305787. The drug-like compounds MMV020549 and MMV666069 also showed promising activities in functional assays. Thus, our study suggests further evaluation of antimalarial compounds as a novel class of antimetastatic agents for the treatment of metastatic osteosarcoma. Twit Text FOAVip Identification of Novel Ezrin Inhibitors Targeting Metastatic Osteosarcoma by Screening Open Access Malaria Box ????Mol Cancer Ther http://www.kidney.de/pget.php?&tw=1&pmid=26358752 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26358752 #FOAvip English Wikipedia <ref>{{Cite pmid|26358752 }}</ref> Identification of Novel Ezrin Inhibitors Targeting Metastatic Osteosarcoma by Screening Open Access Malaria Box #MMPMID26358752 Çelik H ; Hong SH ; Colón-López DD ; Han J ; Kont YS ; Minas TZ ; Swift M ; Paige M ; Glasgow E ; Toretsky JA ; Bosch J ; Üren A Mol Cancer Ther 2015[Nov]; 14 (11 ): 2497-507 PMID26358752 show ga Ezrin is a member of the ERM (ezrin, radixin, moesin) family of proteins and functions as a linker between the plasma membrane and the actin cytoskeleton. Ezrin is a key driver of tumor progression and metastatic spread of osteosarcoma. We discovered a quinoline-based small molecule, NSC305787, that directly binds to ezrin and inhibits its functions in promoting invasive phenotype. NSC305787 possesses a very close structural similarity to commonly used quinoline-containing antimalarial drugs. On the basis of this similarity and of recent findings that ezrin has a likely role in the pathogenesis of malaria infection, we screened antimalarial compounds in an attempt to identify novel ezrin inhibitors with better efficacy and drug properties. Screening of Medicines for Malaria Venture (MMV) Malaria Box compounds for their ability to bind to recombinant ezrin protein yielded 12 primary hits with high selective binding activity. The specificity of the hits on ezrin function was confirmed by inhibition of the ezrin-mediated cell motility of osteosarcoma cells. Compounds were further tested for phenocopying the morphologic defects associated with ezrin suppression in zebrafish embryos as well as for inhibiting the lung metastasis of high ezrin-expressing osteosarcoma cells. The compound MMV667492 exhibited potent anti-ezrin activity in all biologic assays and had better physicochemical properties for drug-likeness than NSC305787. The drug-like compounds MMV020549 and MMV666069 also showed promising activities in functional assays. Thus, our study suggests further evaluation of antimalarial compounds as a novel class of antimetastatic agents for the treatment of metastatic osteosarcoma. |Adamantane/*analogs & derivatives/pharmacology [MESH] |Animals [MESH] |Antimalarials/pharmacology [MESH] |Antineoplastic Agents/*pharmacology [MESH] |Cell Line, Tumor [MESH] |Cell Movement/drug effects [MESH] |Cell Survival/drug effects [MESH] |Cytoskeletal Proteins/*antagonists & inhibitors/metabolism [MESH] |Drug Evaluation, Preclinical/methods [MESH] |Embryo, Nonmammalian/drug effects/embryology/metabolism [MESH] |Immunoblotting [MESH] |Lung Neoplasms/prevention & control/secondary [MESH] |Mice, Inbred BALB C [MESH] |Osteosarcoma/*drug therapy/metabolism/pathology [MESH] |Quinolines/*pharmacology [MESH] |Small Molecule Libraries/pharmacology [MESH] |Surface Plasmon Resonance [MESH]Identification of Novel Ezrin Inhibitors Targeting Metastatic Osteosar(epmc).pdf DeepDyve Pubget Overpricing