Clock Biology

The Core Clock

Your body’s internal clock is a time-keeping system that generates 24-hour rhythms in behavior and physiology in tune with the day-night cycle.

Core-clock proteins are found throughout the body and maintain rhythms in metabolism, blood pressure, immune function, the cardiovascular system, central nervous system function, and myriad other processes.  Clock dysregulation, for example from shift work, increases risk of a broad range of diseases, including cancer.

Core Clock

The Core Clock Regulates Gene Expression

Hundreds or even thousands of genes in each cell and tissue have a daily rhythm of expression that is governed by the core BMAL1/CLOCK transcription protein dimer. 

Clock-regulated proteins differ from tissue to tissue, as well as in sickness and in health. In cancers, BMAL1/CLOCK can be usurped to drive an inappropriate set of proteins that support cancer growth.

Synchronicity Pharma is focused on developing drugs that address clock dysregulation, thereby stopping or reversing the course of cancer progression.

The core clock regulates cancer
The core clock balance and SPI drugs

How can we do this? We do it by tipping the scales on clock dysregulation in cancer

How does the core clock mechanism function?

The animation below illustrates how the BMAL1/CLOCK dimer is subject to two primary feedback loops. Synchronicity’s Founders discovered many elements of the core clock and its control in mammals.

  • The first, involving the PER and CRY proteins, inhibits BMAL1/CLOCK activity by sequestering them and preventing transcription.
  • The second, involving the REV-ERB proteins, inhibits BMAL1 expression in the first place by blocking the ROR-driven transcription of the BMAL1 gene.

Cancer cells are particularly sensitive to loss of clock function and can be targeted by drugs that stabilize either the positive or negative feedback loops.