Abstract：
:Target concentration is typically not considered in drug discovery. However, if targets are expressed at relatively high concentrations and compounds have high affinity, such that most of the drug is bound to its target, in vitro screens can give unreliable information on compound affinity. In vivo, a similar situation will generate pharmacokinetic (PK) profiles that deviate greatly from those normally expected, owing to target binding affecting drug distribution and clearance. Such target-mediated drug disposition (TMDD) effects on small molecules have received little attention and might only become apparent during clinical trials, with the potential for data misinterpretation. TMDD also confounds human microdosing approaches by providing therapeutically unrepresentative PK profiles. Being aware of these phenomena will improve the likelihood of successful drug discovery and development.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Smith DA,van Waterschoot RAB,Parrott NJ,Olivares-Morales A,Lavé T,Rowland Mdoi
10.1016/j.drudis.2018.06.010subject
Has Abstractpub_date
2018-12-01 00:00:00pages
2023-2030issue
12eissn
1359-6446issn
1878-5832pii
S1359-6446(18)30083-7journal_volume
23pub_type
杂志文章,评审abstract：:Monitor provides an insight into the latest developments in drug discovery through brief synopses of recent presentations and publications together with expert commentaries on the latest technologies. There are two sections: Molecules summarizes the chemistry and the pharmacological significance and biological relevan...
journal_title：Drug discovery today
pub_type： 杂志文章
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journal_title：Drug discovery today
pub_type： 杂志文章,评审
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abstract：:Monitor provides an insight into the latest developments in drug discovery through brief synopses of recent presentations and publications together with expert commentaries on the latest technologies. There are two sections: Molecules summarizes the chemistry and the pharmacological significance and biological relevan...
journal_title：Drug discovery today
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journal_title：Drug discovery today
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journal_title：Drug discovery today
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journal_title：Drug discovery today
pub_type： 杂志文章,评审
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journal_title：Drug discovery today
pub_type： 新闻
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journal_title：Drug discovery today
pub_type： 杂志文章,评审
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journal_title：Drug discovery today
pub_type： 杂志文章,评审
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journal_title：Drug discovery today
pub_type： 杂志文章,评审
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journal_title：Drug discovery today
pub_type： 杂志文章,评审
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abstract：:'Many professional scientists over the years have expressed their thoughts and ideas in poetry.' ...
journal_title：Drug discovery today
pub_type： 杂志文章
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journal_title：Drug discovery today
pub_type： 杂志文章
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journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2006.09.010
更新日期：2006-11-01 00:00:00
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journal_title：Drug discovery today
pub_type： 杂志文章,评审
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journal_title：Drug discovery today
pub_type： 杂志文章,评审
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更新日期：2017-07-01 00:00:00
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journal_title：Drug discovery today
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journal_title：Drug discovery today
pub_type： 杂志文章,评审
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更新日期：2004-04-01 00:00:00
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journal_title：Drug discovery today
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journal_title：Drug discovery today
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journal_title：Drug discovery today
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journal_title：Drug discovery today
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journal_title：Drug discovery today
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journal_title：Drug discovery today
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journal_title：Drug discovery today
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journal_title：Drug discovery today
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abstract：:The occurrence of drug resistance in oncology accounts for treatment failure and relapse of diverse tumor types. Cancers contain cells at various stages of differentiation together with a limited number of 'cancer-initiating cells' able to self-renew and divide asymmetrically, driving tumorigenesis. Cancer-initiating ...
journal_title：Drug discovery today
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journal_title：Drug discovery today
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abstract：:In this review, we discuss the methodologies and platform technologies for enhancing the oral bioavailability of poorly soluble drugs. We also highlight the mechanisms of formulation technologies for improving desired physicochemical attributes of active substances. We focus on various commercial technologies, along w...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
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abstract：:For many years, there has been spirited debate as to the relative importance of environmental and genetic factors in the pathogenesis of cancer. Current efforts to annotate the human genome for germ-line genetic variants should establish the foundation for dissecting the contribution of genetics to the risk for cancer...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(04)03179-4
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