The frequent occurrence of multidrug resistance (MDR) conferred by the 
overexpression of ATP-binding cassette (ABC) transporters ABCB1 and ABCG2 in 
cancer cells remains a therapeutic obstacle for scientists and clinicians. 
Consequently, developing or identifying modulators of ABCB1 and ABCG2 that are 
suitable for clinical practice is of great importance. Therefore, we have 
explored the drug repositioning approach to identify candidate modulators of 
ABCB1 and ABCG2 from tyrosine kinase inhibitors with known pharmacological 
properties and anticancer activities. In this study, we discovered that 
avapritinib (BLU-285), a potent, selective, and orally bioavailable tyrosine 
kinase inhibitor against mutant forms of KIT and platelet-derived growth factor 
receptor alpha (PDGFRA), attenuates the transport function of both ABCB1 and 
ABCG2. Moreover, avapritinib restores the chemosensitivity of ABCB1- and 
ABCG2-overexpressing MDR cancer cells at nontoxic concentrations. These findings 
were further supported by results of apoptosis induction assays, ATP hydrolysis 
assays, and docking of avapritinib in the drug-binding pockets of ABCB1 and 
ABCG2. Altogether, our study highlights an additional action of avapritinib on 
ABC drug transporters, and a combination of avapritinib with conventional 
chemotherapy should be further investigated in patients with MDR tumors.