Inositol phospholipid pathway inhibitors and regulators Inositol phospholipid pathway inhibitors and regulators

Abstract

In health and disease, physiological homeostasis depends on the ability of cells to respond to the environment and other cells. Communications between cells are mediated by a variety of chemical signals such as hormones, growth factors, neurotransmitters or electric signals [1]. Although chemical signalling occurs by a number of different mechanisms, signalling molecules can be classified into two general types according to their ability to permeate the plasma membrane. While hydrophobic hormones easily penetrate the lipid bilayer and directly act on intracellular or nuclear receptors, cell impermeant, hydrophilic molecules bind to cell surface receptors embedded in the lipid bilayer and thus generate second messengers that transmit the extracellular signal to the intracellular compartment. In many different cell types, this latter process, referred to as trans-membrane signalling or signal transduction, is mediated by protein phosphorylation cascades, ion fluxes, 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 variety of diseases, including hypertension, diabetes and neuronal disorders, prompting the development of pharmacological agents that re-establish normal inositol signalling. Here, we review the patent literature surrounding small molecule inositol derivatives and discuss the challenges that remain before therapeutic applications become practical.