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2018 ; 10
(5
): ä Nephropedia Template TP
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Identification of circadian clock modulators from existing drugs
#MMPMID29666146
Tamai TK
; Nakane Y
; Ota W
; Kobayashi A
; Ishiguro M
; Kadofusa N
; Ikegami K
; Yagita K
; Shigeyoshi Y
; Sudo M
; Nishiwaki-Ohkawa T
; Sato A
; Yoshimura T
EMBO Mol Med
2018[May]; 10
(5
): ä PMID29666146
show ga
Chronic circadian disruption due to shift work or frequent travel across time
zones leads to jet-lag and an increased risk of diabetes, cardiovascular disease,
and cancer. The development of new pharmaceuticals to treat circadian disorders,
however, is costly and hugely time-consuming. We therefore performed a
high-throughput chemical screen of existing drugs for circadian clock modulators
in human U2OS cells, with the aim of repurposing known bioactive compounds.
Approximately 5% of the drugs screened altered circadian period, including the
period-shortening compound dehydroepiandrosterone (DHEA; also known as
prasterone). DHEA is one of the most abundant circulating steroid hormones in
humans and is available as a dietary supplement in the USA Dietary administration
of DHEA to mice shortened free-running circadian period and accelerated
re-entrainment to advanced light-dark (LD) cycles, thereby reducing jet-lag. Our
drug screen also revealed the involvement of tyrosine kinases, ABL1 and ABL2, and
the BCR serine/threonine kinase in regulating circadian period. Thus, drug
repurposing is a useful approach to identify new circadian clock modulators and
potential therapies for circadian disorders.
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