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In the 2012 Food and Drug Administration (FDA) draft guidance on drug-drug interactions (DDIs), a new molecular entity that inhibits Pglycoprotein (P-gp) may need a clinical DDI study with a P-gp substrate such as digoxin when themaximum concentration of inhibitor at steady state divided by IC50 ([I1]/IC50) is ‡0.1 or concentration of inhibitor based on highest approved dose dissolved in 250 ml...
The structure of a protein depends critically on the complex interactions among its amino acid residues. It has long been hypothesized that interacting residues might tend to coevolve, but it is not known whether such coevolution is a general phenomenon across the proteome. Here, we describe a novel methodology called phylogeny-aided structural analysis, which uncovers robust signals of interac...
Tryptophan metabolites have been linked in observational studies with type 2 diabetes, cognitive disorders, inflammation and immune system regulation. A rate-limiting enzyme in tryptophan conversion is arylformamidase (Afmid), and a double knockout of this gene and thymidine kinase (Tk) has been reported to cause renal failure and abnormal immune system regulation. In order to further investiga...
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