Abstract:
:Billions of US dollars are invested every year by the pharmaceutical industry in drug development, with the aim of introducing new drugs that are effective and have minimal side effects. Thirty percent of in-pipeline drugs are excluded in an early phase of preclinical and clinical screening owing to cardiovascular safety concerns, and several lead molecules that pass the early safety screening make it to market but are later withdrawn owing to severe cardiac side effects. Although the current drug safety screening methodologies can identify some cardiotoxic drug candidates, they cannot accurately represent the human heart in many aspects, including genomics, transcriptomics, and patient- or population-specific cardiotoxicity. Despite some limitations, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a powerful and evolving technology that has been shown to recapitulate many attributes of human cardiomyocytes and their drug responses. In this review, we discuss the potential impact of the inclusion of the hiPSC-CM platform in premarket candidate drug screening.
journal_name
Annu Rev Pharmacol Toxicoljournal_title
Annual review of pharmacology and toxicologyauthors
Magdy T,Schuldt AJT,Wu JC,Bernstein D,Burridge PWdoi
10.1146/annurev-pharmtox-010617-053110subject
Has Abstractpub_date
2018-01-06 00:00:00pages
83-103eissn
0362-1642issn
1545-4304journal_volume
58pub_type
杂志文章,评审abstract::The realization that there exists a multimembered family of cation channels with structural similarity to Drosophila's Trp channel emerged during the second half of the 1990s. In mammals, depending on the species, the TRP family counts 29 or 30 members which has been subdivided into 6 subfamilies on the basis of seque...
journal_title:Annual review of pharmacology and toxicology
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abstract::Originally, organophosphorus (OP) toxicology consisted of acetylcholinesterase inhibition by insecticides and chemical threat agents acting as phosphorylating agents for serine in the catalytic triad, but this is no longer the case. Other serine hydrolases can be secondary OP targets, depending on the OP structure, an...
journal_title:Annual review of pharmacology and toxicology
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journal_title:Annual review of pharmacology and toxicology
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journal_title:Annual review of pharmacology and toxicology
pub_type: 杂志文章,评审
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