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

Characterization of Potent ABCG2 Inhibitor Derived from Chromone: From the Mechanism of Inhibition to Human Extracellular Vesicles for Drug Delivery

“…ABCG2 inhibitors are described to not be specific for a single substrate, but to inhibit the transport activity of protein, abrogating the efflux of different substrates without chemical structural correlation. Here, this feature was investigated, and the data confirmed that C4a is capable of inhibiting different substrates (Figure 4C,D), as recently described for indeno [1,2-b]indoles [17] and porphyrins [18]. C4a also triggered a 5D3-shift, an effect well documented for most ABCG2 inhibitors [47].…”

“…The system was placed in a cubic box with 13X13X15 Å from the box edges to any atom of the protein, using PBC conditions, and, filled with TIP3P [40] water. Systems were equilibrated as previously described [18]. After minimization and relaxing steps, we proceeded with five independent 200 ns runs with randomly generated seeds (in total 1 µs per system).…”

“…Some evidence suggests that the failure of the use of specific P-gp inhibitors was caused by the efflux of drugs mediated by the ABCG2 transporter. Despite the lack of clinical trials using ABCG2 inhibitors, more than a hundred ABCG2 inhibitors have been identified [8], including acridone [13], stilbene [14], chalcone [15], tetrahydroquinoline/4,5-dihydroisoxazole [16], indeno [1,2-b]indole [17], porphyrin [18] and chromone [19] derivatives. Some ABCG2 inhibitors are promising to be used in clinical trials.…”