Inositol phospholipid pathway inhibitors and regulators

In health and disease. physiological homeostasis depends on the ability: of cells to respond to the environment and other cells. Communications betwee n cells are mediated by a variety of chemical signals such as hormones, gro wth factors, neurotransmitters or electric signals [1]. Although chemical s ignalling occurs by a. number of different mechanisms, signalling molecules can be classified into two general types according to their ability to per meate the plasma membrane. While hydrophobic hormones easily penetrate the lipid bilayer and directly act on intracellular or nuclear receptors, cell impermeant, hpdrophilic molecules bind to cell surface receptors embedded i ll the lipid bilayer and thus generate second messengers that transmit the extracellular signal to the intracellular compartment. In many different ce ll types, this latter process, referred to as trans-membrane signalling or signal transduction, is mediated by protein phosphorylation cascades, ion f luxes, as well as changes in the levels of phospholipid breakdown products including diacylglycerol and myo-inositol containing second messengers [2]. Misregulation of inositol signalling pathways has been implicated in a var iety of diseases, including hypertension, diabetes and neuronal disorders, prompting the development of pharmacological agents that re-establish norma l inositol signalling. Here, we review the patent literature surrounding sm all molecule inositol derivatives and discuss the challenges that remain be fore therapeutic applications become practical.