Circadian Biology

Modulating the Clock

Science Signaling  04 Sep 2012:
Vol. 5, Issue 240, pp. ec235
DOI: 10.1126/scisignal.2003547

Because of the close association of the circadian clock with a wide range of physiological processes, identification of clock-modulating small molecules may prove useful for the treatment of circadian-related disorders, which include circadian sleep disorders, cardiovascular disease, cancer, and metabolic disease. Hirota et al. screened for chemical compounds that affected the period of the circadian clock in a human osteosarcoma cell line. A carbazole derivative named KL001 appeared to act by inhibiting proteolytic degradation of the cryptochrome proteins, which in turn caused a lengthening of the circadian period. KL001 also inhibited glucagon-induced gluconeogenesis in primary cultures of mouse hepatocytes.

T. Hirota, J. Wook Lee, P. C. St. John, M. Sawa, K. Iwaisako, T. Noguchi, P. Y. Pongsawakul, T. Sonntag, D. K. Welsh, D. A. Brenner, F. J. Doyle III, P. G. Schultz, S. A. Kay, Identification of small molecule activators of cryptochrome. Science 337, 1094–1097 (2012). [Abstract] [Full Text]