Hot Topics in Drug Development [April 2016]
13
JOURNAL WATCH
future of PPI data analysis. The
a
uthors present the constraints that
they believe have delayed the
transition from the current
methodologies to a holistic
bioinformatics approach for linking
biological and clinical data. They
propose specific solutions for all
these constraints in order to achieve
the optimal exploitation of PPI
bioinformatics' approaches.
*
PMID: PMC4584938
DREADDs: novel tools for drug
discovery and development.
Lee HM, Giguere PM, Roth BL.
Drug Discov Today. 2014
Apr;19(4):469–73. doi:
10.1016/j.drudis.2013.10.018. Epub
2013 Nov 1.
Summary: Here, the authors
discuss how designer receptors
exclusively activated by designer
drugs (DREADDs) can be used as
novel tools for drug discovery and
development. The authors proposed
that DREADDs can facilitate the
identification of druggable targets
and enable researchers to explore
the activities of novel drugs against
both known and orphan GPCRs
*
PMID: 24184433
Using quantitative systems
pharmacology for novel drug
discovery.
Pérez-Nueno VI. Expert Opin Drug
Discov. 2015 Dec;10(12):1315–31.
doi: 10.1517/17460441.2015.1082543.
Epub 2015 Aug 25.
Summary: In this review article,
the authors define quantitative and
systems pharmacology (QSP), a new
paradigm that aims to understand
how drugs modulate cellular
networks in space and time in order
to predict drug targets and their role
in human pathophysiology. The
authors discuss existing
computational and experimental QSP
approaches, such as
polypharmacology techniques
combined with systems biology
i
nformation, and consider the
use of new tools and ideas in a
wider "systems-level"
context in order to
design new drugs
with improved
efficacy and fewer
unwanted off-target
effects.
*
PMID: 26328768
Single-cell analysis tools for
drug discovery and
development.
Heath JR1, Ribas A2, Mischel
PS3.Nat Rev Drug Discov. 2016
Mar;15(3):204-16. doi:
10.1038/nrd.2015.16. Epub 2015 Dec
16.
Summary: Here, researchers
review tools for single-cell genomic,
transcriptomic, and multiplex
proteomic analyses and assess their
advantages and limitations. Emerging
applications of single cell analysis
tools in drug discovery and
development, particularly in the field
of oncology, are discussed.
*
PMID: 26669673
Application of chemical biology
in target identification and drug
discovery.
Zhu Y, Xiao T, Lei S, et al. Arch
Pharm Res. 2015
Sep;38(9):1642–50. doi:
10.1007/s12272-015-0643-2. Epub
2015 Aug 5.
Summary: In this review, the
authors highlight some applications
of chemical biology in the context of
target identification. The authors
explain how chemical biology solves
biological problems through
searching previously unknown
targets for pharmacologically active
small molecules or finding ligands for
well-defined drug targets. They
describe how chemical biology allows
the study of how these small
molecules interact with their
respective targets, as well as their
roles in signal transduction,
molecular recognition and cell
functions. The authors describe
therapeutic targets that are being
identified and validated as a result of
advances in functional genomics.
*
PMID: 26242900
The first structure-activity
relationship studies for designer
receptors exclusively activated
by designer drugs.
Chen X, Choo H, Huang XP, et al.
ACS Chem Neurosci. 2015 Mar
18;6(3):476–84. doi:
10.1021/cn500325v. Epub 2015 Jan
27.
Summary: Here researchers
explored multiple regions of the
scaffold represented by clozapine N-
oxide (CNO), a pharmacologically
inert ligand, identified interesting
structure-activity relationships
(SARs) trends, and discovered
several compounds that are very
potent hM3Dq agonists but do not
activate the native human M3
receptor (hM3). The authors reveal
that the approved drug perlapine is a
novel hM3Dq agonist with >10,000-
fold selectivity for hM3Dq over hM3.
*
PMID: 25587888