Introduction

Compounds potentially effective for the treatment of rare genetic pathologies, characterized by muscular and piastrinic defects, induced by malfunction of the calcium regulation, SOCE. The new class of disclosured molecules, by negative modulation of SOCE, represent the first effective treatment for tubular aggregate myophathy (TAM) or Stormorker and York syndromes, nowadays without care.

Technical features

The patent disclosures a class of small molecules that, by SOCE modulating, reduce the intracellular calcium levels when these are altered. In particular, nowadays, the preclinical data demonstrate that these compounds have all the characteristics to represent an effective care for TAM and other two rare genetic pathologies. These diseases are without treatment, as well as there are not therapeutic approaches in development. Moreover, the described SOCE modulators were demonstrated effective in an animal model of acute pancreatitis, inflammatory event, sometimes lethal, where the calcium overload plays a key role in the emergence of the damage, of the necrosis and in the trypsin activation. Again it is not available a specific pharmaceutical treatment for the patients, but only symptomatic therapies. Only the CM4620, a SOCE modulator, is under II phase of clinical study.

Possible Applications

• TAM, Stormorken and York platelet syndromes, three ultra-rare genetic diseases that carry out the loss of motorial capacity;
• Acute pancreatitis, inflammatory event, rare, pancreas involved, sometimes lethal;
• Other rare pathologies characterised from a calcium overload.

Advantages

• From abnormal to physiologic calcium level;
• Absence of cytotoxicity at effective concentration;
• High selectivity for Orai and STIM proteins;
• Good metabolic stability in vivo;
• High synthetic feasibility.