Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

Wang, K.; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu‐Feng; He, Lin

doi:10.1016/j.bbrc.2014.12.096

Cited by 19 publications

(15 citation statements)

References 46 publications

(31 reference statements)

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“…Also, they were able to identify drugs with FDA boxed warnings for safety liability effectively. Therefore, it illustrates that a combination of effective computational methods and drug-induced gene expression change can be proven as new cutting edge to have a systematic drug safety evaluation [104].…”

Section: Experimental Validationsmentioning

confidence: 99%

A review of connectivity map and computational approaches in pharmacogenomics

et al. 2017

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Large-scale perturbation databases, such as Connectivity Map (CMap) or Library of Integrated Network-based Cellular Signatures (LINCS), provide enormous opportunities for computational pharmacogenomics and drug design. A reason for this is that in contrast to classical pharmacology focusing at one target at a time, the transcriptomics profiles provided by CMap and LINCS open the door for systems biology approaches on the pathway and network level. In this article, we provide a review of recent developments in computational pharmacogenomics with respect to CMap and LINCS and related applications.

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Section: Experimental Validationsmentioning

confidence: 99%

A review of connectivity map and computational approaches in pharmacogenomics

et al. 2017

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“…For instance, it has been well known that drug could induce adverse reactions by unexpectedly interacting with off-target proteins and perturbing downstream signaling pathways. Therefore, the off-targets [50, 51] and genomic expression changes [52, 53] related to finasteride could be further explored. Moreover, it should be noticed that finasteride was approved by FDA for oral use, while minoxidil was approved for topical use.…”

Section: Discussionmentioning

confidence: 99%

Differences in reproductive toxicology between alopecia drugs: an analysis on adverse events among female and male cases

2016

Oncotarget

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Alopecia is a dermatological condition with limited therapeutic options. Only two drugs, finasteride and minoxidil, are approved by FDA for alopecia treatment. However, little is known about the differences in adverse effects between these two drugs. We examined the clinical reports submitted to the FDA Adverse Event Reporting System (FAERS) from 2004 to 2014. For both female and males, finasteride was found to be more associated with reproductive toxicity as compared to minoxidil. Among male alopecia cases, finasteride was significantly more concurrent with several forms of sexual dysfunction. Among female alopecia cases, finasteride was significantly more concurrent with harm to fetus and disorder of uterus. In addition, drug-gene network analysis indicated that finasteride could profoundly disturb pathways related to sex hormone signaling and oocyte maturation. These findings could provide clues for subsequent toxicological research. Taken together, this analysis suggested that finasteride could be more liable to various reproductive adverse effects. Some of these adverse effects have yet to be warned in FDA-approved drug label. This information can help improve the treatment regimen of alopecia and post-marketing regulation of drug products.

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“…[22][23][24][25] Recently, we have explored prediction of adverse drug reactions (ADRs) based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. 26 The results show that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. On the basis of such ADR-gene expression association, we have established prediction models for various ADRs, including severe myocardial and infectious events.…”

mentioning

confidence: 87%