Diabetes is one of the world’s most important causes of healthcare expenditure and lost economic growth. The project revolves around the synthesis and pharmacological evaluation (evaluation of drug properties such as efficacy, tolerance and how it works in the body) of the new compounds from the so-called inhibitors of the sEH (soluble Epoxide Hydrolase) enzime as drugs for the treatment of type 2 diabetes-related conditions, such as metabolic syndrome, cardiovascular problems or neuropathic pain.
- To define the strategy for the development of selected sEH inhibitors, confirming their selectivity and non-citotoxicity, verifying that they are more stable than the previously known sEH inhibitors, and to carry out preliminary efficacy studies in animal models.
Problem to Solve
Cardiovascular, inflammatory and metabolic diseases are the main causes of death worldwide. Type 2 diabetes and metabolic syndrome is a complex health disorder that currently affects around 15% of the worldwide population and current trends show that the disease is affecting younger age groups, steadily increasingly in adolescents and even children.
These conditions are probably one of the most significant economic and health burden for our society, not only from a high prevalence but, even more importantly, for their related chronic complications and high mortality rate. In fact, nowadays it is the fourth worldwide death cause and the trend is on raise.
To develop a new drug for these conditions will benefit the large population currently suffering from them, fulfilling a largely unmet clinical need and improving their quality of life. Additionally, as these disorders are, from an economical point of view, a heavy burden for the Health system of the developed countries, new drugs against these diseases are desperately sought out.
sEH is an enzyme found within cells whose inhibition has recently shown beneficial effects in cardiovascular (hypertension, atherosclerosis, ischaemic heart disease), inflammatory (chronic obstructive pulmonary disease, renal inflammation), and metabolic diseases (diabetes type 2, metabolic syndrome) in several animal models. We have recently synthesized a series of novel potent sEH inhibitors which clearly surpass the previously known sEH inhibitors.
Level of InnovationCurrent sEH inhibitors suffer from low solubility, poor pharmacokinetics and formulation problems. The novel sEH inhibitors are more soluble (being easier to be excreted), less lipophilic (therefore not reabsorbed during the excretory process), and even more potent than reference sHE inhibitors, and may benefit from the fact that most sEHIs are seen in the scientific community as secure drugs, with very few side-effects. Moreover, the novel sHE inhibitors have a extremely short and simple synthesis, so the drug would be of low production cost. Currently, there are several other kind of drugs clinically approved for the treatment of metabolic diseases. Of note, in treating diabetes, combination therapy is usually a need, so a new drug, as the currently sEHIs under study, would not have to compete against the other drugs, but should join them in the therapeutic arsenal. Finally, it must be added that the anti-inflammatory role of sEHIs has been demonstrated in animal models of several orphan diseases (or rare diseases), which may open the way of an orphan drug designation for our novel sEHIs.