THE NUCLEUS OF KARO BIO’S RESEARCH
Within the body, numerous signaling systems exist to enable organs, tissues and cells to communicate. One such system is the hormonal system. Hormones are generally produced in one organ and transported via the blood stream to one or several target organs and tissues.

In the target organ, the hormone binds to certain proteins, called receptors. These receptors are located either on the cell surface or within the cell. The intracellular receptors are known as nuclear receptors. Nuclear receptors regulate the transcription of genes into proteins. Cortisol is one example of a nuclear receptor-binding hormone. It is excreted from the adrenals and acts in a number of target organs and tissues. For instance in an inflamed tissue, cortisol will ease the inflammation by down-regulation of the pro-inflammatory proteins and up-regulation of anti-inflammatory factors. The liver is another example of a target organ for cortisol. Here the hormone regulates the expression of proteins involved in glucose production and thereby increases plasma glucose. Hence it is evident that the same hormone-nuclear receptor complex can have different effects in different target tissues.

To date, 48 nuclear receptors relevant to man have been identified. Some of these are activated or inhibited by hormones, others by vitamins, fatty acids or bile acids. In some cases, the natural signaling molecule, the so-called ligand, has yet to be identified. The nuclear receptors contain binding pockets, where the natural ligands fit. Knowledge about the size and shape of these pockets can be utilized for drug design. Compounds that bind to the nuclear receptor in a similar manner as the natural ligands, and thereby affect gene expression and protein levels, are useful in a number of diseases and medical conditions. One example is the glucocorticoids, a class of compounds acting on the same receptor as cortisol described above. These compounds are much used in inflammatory conditions such as asthma, rheumatoid arthritis and inflammatory bowel disease.

Several of the nuclear receptors are suitable as targets for new pharmaceuticals, within a broad spectrum of therapeutic areas. Karo Bio has extensive know-how, built on many years experience within the field, and the necessary tools to effectively address some of the most interesting nuclear receptors within the company’s drug development projects.