INNOVATIVE TARGETS FOR CIRCADIAN DRUG DISCOVERY: REV-ERBALPHA AND RORALPHA

  • Tomkinson, Nicholas (Principal Investigator)
  • Bresciani, Stefano, (Fellow)
  • Wojno, Justyna, (Fellow)

Project: Research

Description

Humans are rhythmic beings, with daily sleep/wake cycles affecting almost every aspect of physiology and behaviour. Our master circadian clock is known to reside in the suprachiasmatic nuclei (SCN) of the hypothalamus. Via multiple pathways, output from the SCN synchronizes peripheral oscillators throughout the body. The discovery of the molecular components of the core clock has provided new insight into the link between circadian biology and chronic diseases, but has not been exploited for drug discovery. With this work we will prepare chemical probes for the clock proteins REV-ERBalpha and RORalpha, characterise their activity in models of inflammation, and deliver lead optimised molecules for clinical development.

Key findings

"Delivered optimised agonist and antagonist probes suitable for in vivo studies for the nuclear receptor REV-ERBalpha.
These have been delivered to collaborators for biological evaluation where impact of research will be realised."
StatusFinished
Effective start/end date1/07/1131/12/14

Funding

  • EPSRC (Engineering and Physical Sciences Research Council): £1,210,241.00

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Suprachiasmatic Nucleus
Drug Discovery
Circadian Clocks
Cytoplasmic and Nuclear Receptors
Hypothalamus
Sleep
Chronic Disease
Inflammation
Proteins