887593-96-6Relevant articles and documents
Implementation of the CYP Index for the Design of Selective Tryptophan-2,3-dioxygenase Inhibitors
Castanedo, Georgette M.,Dement, Kevin,Dipasquale, Antonio,Gazzard, Lewis,Goon, Leanne,Gustafson, Amy,Harris, Seth F.,Jaipuri, Firoz A.,Kumar, Sanjeev,La, Hank,Li, Xiaokai,Liu, Wen,Liu, Yichin,Mautino, Mario R.,Mendonca, Rohan,Oh, Angela J.,Parr, Brendan T.,Pastor, Richard,Pavana, Roheeth K.,Pei, Zhonghua,Potturi, Hima,Sellers, Benjamin D.,Shao, Cheng,Vanderporten, Erica C.,Velvadapu, Venkata,Waldo, Jesse P.,Wu, Guosheng,Yuen, Po-Wai,Zhang, Yamin,Zhang, Zuhui
, p. 541 - 549 (2020)
A class of imidazoisoindole (III) heme-binding indoleamine-2,3-dioxygenase (IDO1) inhibitors were optimized via structure-based drug design into a series of tryptophan-2,3-dioxygenase (TDO)-selective inhibitors. Kynurenine pathway modulation was demonstrated in vivo, which enabled evaluation of TDO as a potential cancer immunotherapy target. As means of mitigating the risk of drug-drug interactions arising from cytochrome P450 inhibition, a novel property-based drug design parameter, herein referred to as the CYP Index, was implemented for the design of inhibitors with appreciable selectivity for TDO over CYP3A4. We anticipate the CYP Index will be a valuable design parameter for optimizing CYP inhibition of any small molecule inhibitor containing a Lewis basic motif capable of binding heme.
2-AMINOPYRIDINE ANALOGS AS GLUCOKINASE ACTIVATORS
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Page/Page column 120, (2008/12/04)
Provided are compounds that are useful in the treatment and/or prevention of diseases mediated by deficient levels of glucokinase activity, such as diabetes mellitus. Also provided are methods of treating or preventing diseases and disorders characterized by underactivity of glucokinase or which can be treated by activating glucokinase.
