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10.1021/jm7014155 http://scihub22266oqcxt.onion/10.1021/jm7014155 C4384695!4384695 !18318466     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=18318466 &cmd=llinks): Failed to open stream: HTTP request failed! 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Indoleamine 2,3-dioxygenase is the anticancer target for a novel series of potent naphthoquinone-based inhibitors |pdf=|usr=}}{{18318466 }} gab.com Text Indoleamine 2,3-dioxygenase is the anticancer target for a novel series of potent naphthoquinone-based inhibitors JO: J Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=18318466 #FOAvip Indoleamine 2,3-dioxygenase (IDO) is emerging as an important new therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. While small molecule inhibitors of IDO exist, there remains a dearth of high-potency compounds offering in vivo efficacy and clinical translational potential. In this study, we address this gap by defining a new class of naphthoquinone-based IDO inhibitors exemplified by the natural product menadione, which is shown in mouse tumor models to have similar antitumor activity to previously characterized IDO inhibitors. Genetic validation that IDO is the critical in vivo target is demonstrated using IDO-null mice. Elaboration of menadione to a pyranonaphthoquinone has yielded low nanomolar potency inhibitors, including new compounds which are the most potent reported to date (K(i) = 61-70 nM). Synthetic accessibility of this class will facilitate preclinical chemical-genetic studies as well as further optimization of pharmacological parameters for clinical translation. Twit Text FOAVip Indoleamine 2,3-dioxygenase is the anticancer target for a novel series of potent naphthoquinone-based inhibitors ????J Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=18318466 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=18318466 #FOAvip English Wikipedia <ref>{{Cite pmid|18318466 }}</ref> Indoleamine 2,3-dioxygenase is the anticancer target for a novel series of potent naphthoquinone-based inhibitors #MMPMID18318466 Kumar S ; Malachowski WP ; DuHadaway JB ; LaLonde JM ; Carroll PJ ; Jaller D ; Metz R ; Prendergast GC ; Muller AJ J Med Chem 2008[Mar]; 51 (6 ): 1706-18 PMID18318466 show ga Indoleamine 2,3-dioxygenase (IDO) is emerging as an important new therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. While small molecule inhibitors of IDO exist, there remains a dearth of high-potency compounds offering in vivo efficacy and clinical translational potential. In this study, we address this gap by defining a new class of naphthoquinone-based IDO inhibitors exemplified by the natural product menadione, which is shown in mouse tumor models to have similar antitumor activity to previously characterized IDO inhibitors. Genetic validation that IDO is the critical in vivo target is demonstrated using IDO-null mice. Elaboration of menadione to a pyranonaphthoquinone has yielded low nanomolar potency inhibitors, including new compounds which are the most potent reported to date (K(i) = 61-70 nM). Synthetic accessibility of this class will facilitate preclinical chemical-genetic studies as well as further optimization of pharmacological parameters for clinical translation. |Animals [MESH] |Antineoplastic Agents/chemical synthesis/chemistry/*pharmacology [MESH] |Binding Sites [MESH] |Cell Proliferation/drug effects [MESH] |Cell Survival/drug effects [MESH] |Computer Simulation [MESH] |Crystallography, X-Ray [MESH] |Disease Models, Animal [MESH] |Dose-Response Relationship, Drug [MESH] |Drug Screening Assays, Antitumor [MESH] |Enzyme Inhibitors/chemical synthesis/chemistry/*pharmacology [MESH] |Indoleamine-Pyrrole 2,3,-Dioxygenase/*antagonists & inhibitors/genetics [MESH] |Mice [MESH] |Mice, Knockout [MESH] |Mice, Nude [MESH] |Models, Molecular [MESH] |Molecular Structure [MESH] |Naphthoquinones/chemical synthesis/chemistry/*pharmacology [MESH] |Pyrones/chemistry/pharmacology [MESH] |Stereoisomerism [MESH] |Structure-Activity Relationship [MESH]Indoleamine 2,3-dioxygenase is the anticancer target for a novel serie(epmc).pdf DeepDyve Pubget Overpricing