1.1 Targets Are Diverse
To be able to comprehend the challenges lying ahead on the way to drug design/
drug discovery, it is important to understand the diversity of the drug targets that
have been exploited so far as well as the trend in new drug targets in recent history
of drug discovery [21]. Mathias Rask-Andersen et al. performed a study on all
drugs approved by FDA during 1983–2010. They took all 1542 drug entries as on
May 2009 and filtered out 225 drugs with unknown targets, 192 with no human
targets, and 609 non-therapeutic targets to yield a dataset of 435 therapeutic
effect-mediating targets for humans and to account for the time lag between drug
approval and their entry in DrugBank; drugs approved during 2007–2010 were
taken from FDA data and included for analysis. Drug–target association was
annotated by manual curation from literature data, and targets were kept in four
classes (receptors, enzymes, transporters, and others) with receptor class has highest
193 targets, followed by enzymes with 124, transporters with 67, and others with 51
targets [21]. Analyzing curated drug–target association dataset, they found that
every year 17.9 drugs targeting human proteins are approved by FDA, while 4.3 of
them act on novel targets. The trend in FDA approval of drugs targeting new human
proteins (novel target drugs: NTDs) does not decrease overall. Moreover, they
noticed three peaks corresponding to durations 1990–1993, 1994–2000, and 2001–
2008 when NTDs were plotted against years from 1983 to 2010; they called them
first-, second-, and third-target “innovation peaks,” respectively [21].
During the first innovation peak, it was observed that proportions of approved
drugs for all major target groups—GPCRs, hydrolases, transferases, and isomerases
—were similar to other two peaks. During second innovation peak, first time
integrins appeared as drug target, while during the third innovation peak, asthma
drug omalizumab-targeted Fc-receptors and imatinib appeared as kinase inhibitor
[21].
Analysis of novel targets for drugs with time by Mathias Rask-Andersen et al.
highlights the fact that with the passing time new drugs apart from targets belonging
to earlier exploited classes, novel classes of targets are also being identified for new
drugs. Thus, diversity in the classes of target molecules is expanding, and SBDD
practices have to be optimized to improve success rates in such studies. Present
review will attempt to enlighten and discuss the solutions for such relevant topics
including the challenges upcoming ahead.
1.2 Targets Are More Diverse than Earlier
Genomic-wide association studies over a set of druggable genome, utilizing
bioactivity data including approved drugs or clinical compounds and gene association data against these targets, can be used to come up with set of further druggable
genes and gene combinations as target [22]. Recently in 2017, Finan et al. have
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S. K. Panday and I. Ghosh
To be able to comprehend the challenges lying ahead on the way to drug design/
drug discovery, it is important to understand the diversity of the drug targets that
have been exploited so far as well as the trend in new drug targets in recent history
of drug discovery [21]. Mathias Rask-Andersen et al. performed a study on all
drugs approved by FDA during 1983–2010. They took all 1542 drug entries as on
May 2009 and filtered out 225 drugs with unknown targets, 192 with no human
targets, and 609 non-therapeutic targets to yield a dataset of 435 therapeutic
effect-mediating targets for humans and to account for the time lag between drug
approval and their entry in DrugBank; drugs approved during 2007–2010 were
taken from FDA data and included for analysis. Drug–target association was
annotated by manual curation from literature data, and targets were kept in four
classes (receptors, enzymes, transporters, and others) with receptor class has highest
193 targets, followed by enzymes with 124, transporters with 67, and others with 51
targets [21]. Analyzing curated drug–target association dataset, they found that
every year 17.9 drugs targeting human proteins are approved by FDA, while 4.3 of
them act on novel targets. The trend in FDA approval of drugs targeting new human
proteins (novel target drugs: NTDs) does not decrease overall. Moreover, they
noticed three peaks corresponding to durations 1990–1993, 1994–2000, and 2001–
2008 when NTDs were plotted against years from 1983 to 2010; they called them
first-, second-, and third-target “innovation peaks,” respectively [21].
During the first innovation peak, it was observed that proportions of approved
drugs for all major target groups—GPCRs, hydrolases, transferases, and isomerases
—were similar to other two peaks. During second innovation peak, first time
integrins appeared as drug target, while during the third innovation peak, asthma
drug omalizumab-targeted Fc-receptors and imatinib appeared as kinase inhibitor
[21].
Analysis of novel targets for drugs with time by Mathias Rask-Andersen et al.
highlights the fact that with the passing time new drugs apart from targets belonging
to earlier exploited classes, novel classes of targets are also being identified for new
drugs. Thus, diversity in the classes of target molecules is expanding, and SBDD
practices have to be optimized to improve success rates in such studies. Present
review will attempt to enlighten and discuss the solutions for such relevant topics
including the challenges upcoming ahead.
1.2 Targets Are More Diverse than Earlier
Genomic-wide association studies over a set of druggable genome, utilizing
bioactivity data including approved drugs or clinical compounds and gene association data against these targets, can be used to come up with set of further druggable
genes and gene combinations as target [22]. Recently in 2017, Finan et al. have
112
S. K. Panday and I. Ghosh