Selecting for somatostatin receptors
of the somatostatin receptor - subtypes 1 and 4 - with potential in
a wide range of disease indications.
A Finnish company has identified small-molecule inhibitors of two forms of the somatostatin receptor - subtypes 1 and 4 - and believes this could spark new interest in drugs that mediate the hormone's activity.
Juvantia Pharmaceuticals has discovered a series of compounds which bind to the receptor subtypes with high affinity, have a low molecular weight and are likely to be orally-bioavailable. They could have a role to play in a number of central and peripheral nervous system applications, according to the firm.
"Somatostatin receptors are common and widely distributed in the human body, [but] this receptor family is one of the least exploited biological mediators in clinical therapy," said the company.
The hormone was first discovered in hypothalamic extracts and found to inhibit the secretion of growth hormone. Subsequently, somatostatin was found to be secreted by a broad range of tissues, including the pancreas, intestinal tract and regions of the central nervous system outside the hypothalamus.
Five different subtypes of somatostatin receptors have been characterised, all of which are members of the G protein-coupled receptor superfamily. Somatostatin receptors are divided in two distinct subfamilies, the 2, 3 and 5 subtypes (SSTR-2,3,5) representing one and the 1 and 4 subtypes (SSTR-1,4) representing the other.
Studies of the role of the SSTR-1,4 group has until now been held back by a lack of compounds that exhibit enough selectivity for this group over the SSTR-2,3,5 subfamily.
"Somatostatin and its peptide analogues have long been used to treat neoplasms and, due to their ability to inhibit growth hormone secretion, also giantism and acgromegaly," according to Dr Juha-Matti Savola, CEO of the Finnish company. Juvantia's subtype 1 and 4-targetted drugs may address much broader markets and avoid the unwanted side effects related to classical somatostatin functions, she added.
Juvantia's compounds could extend the use of somatostatin modulators into new indications such as diabetic angiopathy and retinopathy, angiogenesis, vascular restenosis and wound healing, noted Dr Savola.
