Small Synthetic Molecule (KL044) Binds to CRY Protein & Slows Down Circadian Clock; Finding May Guide Future Studies to Develop New Drugs for Clock-Related Disorders & Diseases

A group of biologists, theoretical chemists, and synthetic chemists at the Institute of Transformative Bio-Molecules (ITbM) at Nagoya University in Japan have come together to develop a small molecule that slows down the circadian clock rhythm through binding to the cryptochrome (CRY) clock protein. Almost every aspect of our life varies over time: we wake up in the morning, sleep at night, and become hungry at about the same time every day. These biological processes that occur over time are called the circadian rhythm; an approximately 24-hour cycle regulated by the circadian clock, which is an interplay between and among genes and proteins in every cell of the body. The circadian clock regulates many physiological processes, such as body temperature, metabolism, and hormone secretion. Various environmental factors, including sunlight and temperature, affect the circadian clock. Furthermore, the circadian clock can be disturbed by modern lifestyle changes, such as shift work or long-distance flights, which, in turn, can lead to sleep or metabolic disorders. Understanding how the circadian clock works and how it affects our physiology is therefore vital to understanding and finding treatments for these disorders. Dr. Tsuyoshi Hirota and Dr. Steve Kay of the University of Southern California previously discovered a small molecule named KL001 (a compound discovered at the “Kay Laboratory”) that binds to the CRY protein, an essential component of the circadian clock. KL001 prevents degradation of CRY and slows down the speed of the circadian clock. In the current study, published in the September 2015 issue of the journal ChemMedChem, the group led by Dr. Hirota, Dr. Kay, Dr. Anupriya Kumar, and Dr.
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