A new porphyrin as selective substrate-based inhibitor of breast cancer resistance protein (BCRP/ABCG2).

ABSTRACT: The ABCG2 transporter plays a pivotal role in multidrug resistance, however, no clinical trial using specific ABCG2 inhibitors have been successful. Although ABC transporters actively extrude a wide variety of substrates, photodynamic therapeutic agents with porphyrinic scaffolds are exclusively transported by ABCG2. In this work, we describe for the first time a porphyrin derivative (4B) inhibitor of ABCG2 and capable to overcome multidrug resistance in vitro. The inhibition was time-dependent and 4B was not itself transported by ABCG2. Independently of the substrate, the porphyrin 4B showed an IC₅₀ value of 1.6 μM and a mixed type of inhibition. This compound inhibited the ATPase activity and increased the binding of the conformational-sensitive antibody 5D3. A thermostability

SUBMITTER: Zattoni IF 

PROVIDER: S-EPMC10263179 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature