Fig. 6.

Model depiction of the role of ponatinib in potentiation of the antifungal efficacy of fluconazole by inhibition of fluconazole efflux via Pdr5 and suppression of Pma1 expression. Ponatinib (PubChem CID: 24826799) promotes intracellular fluconazole (PubChem CID:3365) accumulation by binding to Pdr5. On the other hand, ponatinib perturbs the cytosolic pH homeostasis by inhibiting the proton pump Pma1 located at the plasma membrane. Eventually, the dual action of ponatinib through these two pathways leads to cell death.