The CRY1:CLOCK:BMAL1 sits at the core of the integrated transcription-translation feedback loop that regulates the expression of proteins that are dependent upon circadian rhythms. Disruption of circadian rhythms has been linked to altered cell homeostasis and diseases.
The initial discovery at UC Santa Cruz was that CRY1 interacts with CLOCK via a deep binding pocket. Later it was shown by another group that linked a mutation in this binding pocket with an inherited sleep disorder. The deletion of the exon 11 domain, which contains the mutation, was confirmed experimentally at UC Santa Cruz to block the CRY1:CLOCK interaction.
The UC Santa Cruz group developed and optimized a screening method for inhibitors of the CRY1:CLOCK interaction. Such inhibitors would act as a "reset" of the transcription-translation feedback mechanism and act more directly and rapidly than other drugs that are proposed to elicit such effects.
Screening for drugs that treat circadian rhythm disorders
Novel, validated target for circadian rhythm disorders
|United States Of America||Published Application||20190324032||10/24/2019||2017-260|
Circadian Rhythms, Sleep Disorders, Compound Screening, Novel Drug Targets