{"id":3037,"date":"2018-04-07T08:50:44","date_gmt":"2018-04-07T08:50:44","guid":{"rendered":"https:\/\/www.sygnaturediscovery.com\/technical-note\/cytochrome-p450-inhibition-time-dependent-ic50-shift\/"},"modified":"2018-04-07T08:50:44","modified_gmt":"2018-04-07T08:50:44","slug":"cytochrome-p450-inhibition-time-dependent-ic50-shift","status":"publish","type":"technical-note","link":"https:\/\/www.sygnaturediscovery.com\/fr\/technical-note\/cytochrome-p450-inhibition-time-dependent-ic50-shift\/","title":{"rendered":"Time Dependent Inhibition"},"content":{"rendered":"<p>Time dependent inhibition (TDI) of CYPs refers to a change in enzyme inhibition during an\u00a0<em>in vitro<\/em>\u00a0incubation or dosing period\u00a0<em>in vivo<\/em>.\u00a0<a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17269894\">Riley, Grime and Weaver, Expert Opin Drug Metab Toxicol. 2007 Feb;3(1):51-66.<\/a><\/p>\n<p>TDI can be the cause of serious drug-drug interactions (DDI). TDI is usually measured by comparing potency (IC<sub>50<\/sub>) in direct inhibition to potency after a 30 minute pre-incubation in the absence of NADPH. In the case of a TDI the resulting\u00a0IC<sub>50<\/sub>-value will be significantly lower than the\u00a0IC<sub>50<\/sub>-value observed in the direct inhibition experiment.<\/p>\n<p>The cytochrome P450 (CYP450) enzymes play a significant role in the metabolism of both endogenous and exogenous compounds. Within this family, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 are predominantly involved in the metabolism of drugs.<\/p>\n<p>The measurement of the inhibition of each of these CYP450 enzymes in human liver microsomes (HLM) helps in predicting the potential for drug-drug interactions with co-administered drugs and in understanding the subsequent clinical consequences.<\/p>\n<p>Sygnature\u2019s Standard Time-Dependent CYP450 Inhibition assay (IC<sub>50<\/sub>\u00a0Shift) utilises drug-like probe substrates, HLM and the Phase I cofactor, NADPH and two pre-incubation times, 0 and 30 minutes. The assay monitors for the formation of the metabolites of the drug-like probe substrates in the absence and presence of a compound by LC-MS\/MS following a pre-incubation period. All assays have two replicates per compound and include a positive control inhibitor. Data output consists of the generation of an inhibition constant or IC<sub>50<\/sub>\u00a0value.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Explore Time-Dependent Inhibition (TDI) &#038; Drug Interactions with Sygnature&rsquo;s CYP450 Assay. Predict IC50 Shift &#038; Enzyme Dynamics.<\/p>\n","protected":false},"featured_media":0,"template":"","category":[1],"resource_tag":[],"class_list":["post-3037","technical-note","type-technical-note","status-publish","hentry","category-uncategorized"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Time dependent inhibition (TDI) - Sygnature Discovery<\/title>\n<meta name=\"description\" content=\"Explore Time-Dependent Inhibition (TDI) &amp; Drug Interactions with Sygnature&#039;s CYP450 Assay. 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