iKIX1

BeschreibungiKIX1 is an inhibitor of interactions between the transcription co-activator Mediator complex and the pleitropic drug resistance (CgPdr1) transcription factor in the pathogen C. glabrata. It inhibits the interaction between the KIX domain of the Mediator subunit CgGal11A and the activation domain of CgPdr1 (IC50 = 190.2 μM). iKIX1 (10 and 30 μM) inhibits ketoconazole-induced expression of CgPdr1-target genes involved in multidrug resistance and drug efflux in C. glabrata. It increases the sensitivity of azole-resistant C. glabrata strains expressing CgPDR1 gain-of-function mutations to the antifungal compounds fluconazole and ketoconazole in a concentration-dependent manner. iKIX1 (100 mg/kg) decreases fungal burden in the kidney and spleen in a mouse model of infection with azole-sensitive or -resistant C. glabrata when administered in combination with low and high doses of fluconazole, respectively.