FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2079149444> ?p ?o ?g. }

• W2079149444 endingPage "142" @default.
• W2079149444 startingPage "134" @default.
• W2079149444 abstract "Biomarkers are biometric measurements that provide critical quantitative information about the biological condition of the animal or individual being tested. In drug safety studies, established toxicity biomarkers are used along with other conventional study data to determine dose-limiting organ toxicity, and to define species sensitivity for new chemical entities intended for possible use as human medicines. A continuing goal of drug safety scientists in the pharmaceutical industry is to discover and develop better trans-species biomarkers that can be used to determine target organ toxicities for preclinical species in short-term studies at dose levels that are some multiple of the intended human dose and again later in full development for monitoring clinical trials at lower therapeutic doses. Of particular value are early, predictive, noninvasive biomarkers that have in vitro, in vivo, and clinical transferability. Such translational biomarkers bridge animal testing used in preclinical science and human studies that are part of subsequent clinical testing. Although suitable for in vivo preclinical regulatory studies, conventional hepatic safety biomarkers are basically confirmatory markers because they signal organ toxicity after some pathological damage has occurred, and are therefore not well-suited for short-term, predictive screening assays early in the discovery-to-development progression of new chemical entities (NCEs) available in limited quantities. Efforts between regulatory agencies and the pharmaceutical industry are underway for the coordinated discovery, qualification, verification and validation of early predictive toxicity biomarkers. Early predictive safety biomarkers are those that are detectable and quantifiable prior to the onset of irreversible tissue injury and which are associated with a mechanism of action relevant to a specific type of potential hepatic injury. Potential drug toxicity biomarkers are typically endogenous macromolecules in biological fluids with varying immunoreactivity which can present bioanalytical challenges when first discovered. The potential success of these efforts is greatly enhanced by recent advances in two closely linked technologies, toxicoproteomics and targeted, quantitative mass spectrometry. This review focuses on the examination of the current status of these technologies as they relate to the discovery and development of novel preclinical biomarkers of hepatotoxicity. A critical assessment of the current literature reveals two distinct lines of safety biomarker investigation, (1) peripheral fluid biomarkers of organ toxicity and (2) tissue or cell-based toxicity signatures. Improved peripheral fluid biomarkers should allow the sensitive detection of potential organ toxicity prior to the onset of overt organ pathology. Advancements in tissue or cell-based toxicity biomarkers will provide sensitive in vitro or ex vivo screening systems based on toxicity pathway markers. An examination of the current practices in clinical pathology and the critical evaluation of some recently proposed biomarker candidates in comparison to the desired characteristics of an ideal toxicity biomarker lead this author to conclude that a combination of selected biomarkers will be more informative if not predictive of potential animal organ toxicity than any single biomarker, new or old. For the practical assessment of combinations of conventional and/or novel toxicity biomarkers in rodent and large animal preclinical species, mass spectrometry has emerged as the premier analytical tool compared to specific immunoassays or functional assays. Selected and multiple reaction monitoring mass spectrometry applications make it possible for this same basic technology to be used in the progressive stages of biomarker discovery, development, and more importantly, routine study applications without the use of specific antibody reagents. This technology combined with other omics technologies can provide added selectivity and sensitivity in preclinical drug safety testing." @default.
• W2079149444 created "2016-06-24" @default.
• W2079149444 creator A5006687812 @default.
• W2079149444 date "2010-05-15" @default.
• W2079149444 modified "2023-10-12" @default.
• W2079149444 title "The discovery and development of proteomic safety biomarkers for the detection of drug-induced liver toxicity" @default.
• W2079149444 cites W1518108212 @default.
• W2079149444 cites W1759442301 @default.
• W2079149444 cites W1897615258 @default.
• W2079149444 cites W1963527734 @default.
• W2079149444 cites W1965807926 @default.
• W2079149444 cites W1974500649 @default.
• W2079149444 cites W1984263929 @default.
• W2079149444 cites W1989755866 @default.
• W2079149444 cites W1990340142 @default.
• W2079149444 cites W1992197460 @default.
• W2079149444 cites W1995048715 @default.
• W2079149444 cites W2000380894 @default.
• W2079149444 cites W2001472155 @default.
• W2079149444 cites W2001839732 @default.
• W2079149444 cites W2003531826 @default.
• W2079149444 cites W2004607218 @default.
• W2079149444 cites W2004873541 @default.
• W2079149444 cites W2006574959 @default.
• W2079149444 cites W2007656769 @default.
• W2079149444 cites W2010281379 @default.
• W2079149444 cites W2010399398 @default.
• W2079149444 cites W2012108015 @default.
• W2079149444 cites W2012573067 @default.
• W2079149444 cites W2013206130 @default.
• W2079149444 cites W2015285409 @default.
• W2079149444 cites W2017261472 @default.
• W2079149444 cites W2017409119 @default.
• W2079149444 cites W2017806914 @default.
• W2079149444 cites W2021551481 @default.
• W2079149444 cites W2022715711 @default.
• W2079149444 cites W2022873980 @default.
• W2079149444 cites W2023096047 @default.
• W2079149444 cites W2025067634 @default.
• W2079149444 cites W2030156043 @default.
• W2079149444 cites W2032360034 @default.
• W2079149444 cites W2033506900 @default.
• W2079149444 cites W2035037428 @default.
• W2079149444 cites W2037642325 @default.
• W2079149444 cites W2039719431 @default.
• W2079149444 cites W2042850156 @default.
• W2079149444 cites W2045591383 @default.
• W2079149444 cites W2047329047 @default.
• W2079149444 cites W2051043031 @default.
• W2079149444 cites W2051166614 @default.
• W2079149444 cites W2052193758 @default.
• W2079149444 cites W2053854032 @default.
• W2079149444 cites W2055721927 @default.
• W2079149444 cites W2056467018 @default.
• W2079149444 cites W2059347424 @default.
• W2079149444 cites W2060453618 @default.
• W2079149444 cites W2063769966 @default.
• W2079149444 cites W2065044288 @default.
• W2079149444 cites W2071952376 @default.
• W2079149444 cites W2073730054 @default.
• W2079149444 cites W2074627716 @default.
• W2079149444 cites W2077830007 @default.
• W2079149444 cites W2077883962 @default.
• W2079149444 cites W2078208642 @default.
• W2079149444 cites W2082254241 @default.
• W2079149444 cites W2087324264 @default.
• W2079149444 cites W2089187234 @default.
• W2079149444 cites W2090745313 @default.
• W2079149444 cites W2090927900 @default.
• W2079149444 cites W2091278646 @default.
• W2079149444 cites W2092434173 @default.
• W2079149444 cites W2092612655 @default.
• W2079149444 cites W2094229819 @default.
• W2079149444 cites W2095165118 @default.
• W2079149444 cites W2101454929 @default.
• W2079149444 cites W2103873678 @default.
• W2079149444 cites W2108401997 @default.
• W2079149444 cites W2111494667 @default.
• W2079149444 cites W2112464711 @default.
• W2079149444 cites W2113432838 @default.
• W2079149444 cites W2113766156 @default.
• W2079149444 cites W2117398821 @default.
• W2079149444 cites W2118993244 @default.
• W2079149444 cites W2119235878 @default.
• W2079149444 cites W2120161408 @default.
• W2079149444 cites W2129897014 @default.
• W2079149444 cites W2130595300 @default.
• W2079149444 cites W2131872164 @default.
• W2079149444 cites W2133015359 @default.
• W2079149444 cites W2133279956 @default.
• W2079149444 cites W2139396663 @default.
• W2079149444 cites W2142201529 @default.
• W2079149444 cites W2155844407 @default.
• W2079149444 cites W2156827860 @default.
• W2079149444 cites W2157440617 @default.
• W2079149444 cites W2164610579 @default.
• W2079149444 cites W2165413208 @default.
• W2079149444 cites W2167033601 @default.

• next