<i>In Vitro</i> and <i>In Vivo</i> Interactions of TOR Inhibitor AZD8055 and Azoles against Pathogenic Fungi
Yi Sun, Lihua Tan, Zhaoqian Yao, Lujuan Gao, Ji Yang, Tongxiang Zeng
Abstract
Limited options of antifungals and the emergence of drug resistance in fungal pathogens has been a multifaceted clinical challenge. Combination therapy represents a valuable alternative to antifungal monotherapy. The target of rapamycin (TOR), a conserved serine/threonine kinase from yeast to humans, participates in a signaling pathway that governs cell growth and proliferation in response to nutrient availability, growth factors, and environmental stimuli. AZD8055 is an orally bioavailable, potent, and selective TOR kinase inhibitor that binds to the ATP binding cleft of TOR kinase and inhibits both TORC1 and TORC2. Synergism between AZD8055 and azoles suggested that the concomitant application of AZD8055 and azoles may help to enhance azole therapeutic efficacy and impede azole resistance. TOR inhibitor with fungal specific target is promising to be served as combination regimen with azoles.