Inhibition of alkaline phosphatase: an emerging new drug target

Abstract

Alkaline phosphatase (AP, EC 3.1.3.1.) is a metalloenzyme that belongs to a family of ectonucleotidases. The other members of ectonucleotidase family are ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases), ecto-nucleotide pyrophosphatase/phosphodiesterases (E-NPPs) and ecto-5'-nucleotidase (e5'NT). These ectonucleotidases are responsible for hydrolyzing extracellular nucleotides to nucleosides including adenosine. Many of these extracellular nucleotides and adenosine are important signaling molecules that act on their respective receptors (adenosine activated P1 receptor; nucleotide activated P2 receptor, each having many sub-types) and are therefore responsible for triggering cellular responses that lead to important physiological and immunological changes. A dedicated, concerted cohort of ectonucleotidases is responsible for controlling the availability of these extracellular signaling molecules at their respective receptors. Inhibitors of these ectonucleotidases provide the means by which these cellular processes can be modulated. This mini review has been written in the wake of mounting evidence of potential therapeutic benefits associated with inhibition of alkaline phosphatases and aims to provide prolific leads to design more potent and selective AP inhibitors.