OTOGL Inhibitors

Chemical inhibitors of OTOGL function by interfering with its phosphorylation state, which is essential for its role in the structural maintenance of hair cell stereocilia, crucial for hearing. Phorbol 12-myristate 13-acetate, commonly known as PMA, activates protein kinase C (PKC), a kinase that can phosphorylate OTOGL, leading to its inhibition. Staurosporine, a broad-spectrum kinase inhibitor, prevents various kinases including PKC from phosphorylating OTOGL, thereby inhibiting its function. Similarly, Bisindolylmaleimide I, Gö 6983, and Ro-31-8220 are potent inhibitors of PKC, which means they can prevent the phosphorylation of OTOGL. The specific inhibition of PKC results in reduced phosphorylation and subsequent functional inhibition of OTOGL. Calphostin C, which requires light to bind to PKC's regulatory domain, and Chelerythrine both serve to inhibit PKC's activity, thereby reducing the phosphorylation of OTOGL and inhibiting its function within the hair cells.

Continuing with PKC inhibitors, Sotrastaurin, Ruboxistaurin, and Enzastaurin selectively inhibit PKC, leading to a decrease in OTOGL phosphorylation. This lack of phosphorylation can inhibit OTOGL from maintaining proper hair cell structure and function. Balanol, as an ATP-competitive inhibitor, prevents PKC-and by extension, other kinases-from phosphorylating their target proteins, including OTOGL, which results in functional inhibition. Lastly, C1-10 is a cell-permeable compound that inhibits PKC, and consequentially, the phosphorylation of OTOGL is reduced. Through these various chemical interactions that lead to the decreased activity of PKC or its inhibition, the phosphorylation state of OTOGL is directly impacted, resulting in its functional inhibition and affecting its role in the auditory system.