Interaction of A₃ adenosine receptor ligands with the human multidrug transporter ABCG2.

ABSTRACT: Various adenosine receptor nucleoside-like ligands were found to modulate ATP hydrolysis by the multidrug transporter ABCG2. Both ribose-containing and rigidified (N)-methanocarba nucleosides (C2-, N⁶- and 5'-modified), as well as adenines (C2-, N⁶-, and deaza modified), were included. 57 compounds out of 63 tested either stimulated (50) or inhibited (7) basal ATPase activity. Structure-activity analysis showed a separation of adenosine receptor and ABCG2 activities. The 7-deaza modification had favorable effects in both (N)-methanocarba nucleosides and adenines. Adenine 37c (MRS7608) and (N)-methanocarba 7-deaza-5'-ethyl ester 60 (MRS7343) were found to be potent stimulators of ABCG2 ATPase activity with EC₅₀ values of 13.2 ± 1.7 and 13.2 ± 2.2 nM, respect

SUBMITTER: Abel B 

PROVIDER: S-EPMC8893036 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature