Investigation of Fluorescent Substrates and Substrate-Dependent Interactions of a Drug Transporter Organic Anion Transporting Polypeptide 2B1 (OATP2B1) was written by Kawasaki, Tatsuya;Shiozaki, Yuichi;Nomura, Naoki;Kawai, Kumi;Uwai, Yuichi;Nabekura, Tomohiro. And the article was included in Pharmaceutical Research in 2020.Safety of 2′,7′-Dichloro-3′,6′-dihydroxy-3H-spiro[isobenzofuran-1,9′-xanthen]-3-one This article mentions the following:
Abstract: Purpose: In this study, we investigated organic anion transporting polypeptide 2B1 (OATP2B1)-mediated uptake of fluorescent anions to better identify fluorescent substrates for in vitro OATP2B1 assays. The OATP2B1 is involved in the intestinal absorption and one of the pharmacokinetic determinants of orally administered drugs. Methods: A microplate reader was used to determine the cellular accumulation of the fluorescent compounds into the OATP2B1 or the empty vector-transfected HEK293 cells. Results: Two types of derivatives were found to be OATP2B1 substrates: heavy halogenated derivatives, such as 4′,5′-dibromofluorescein (DBF), and carboxylated derivatives, such as 5-carboxyfluorescein (5-CF). The DBF and 5-CF were transported in a time and concentration-dependent manner. The DBF was transported at a broad pH (pH 6.5-8.0) while 5-CF was transported at an acidic pH (pH 5.5-6.5). The Km values were 0.818 ± 0.067μM at pH 7.4 for DBF and 8.56 ± 0.41μM at pH 5.5 for 5-CF. The OATP2B1 inhibitors, including atorvastatin, bromosulfophthalein, glibenclamide, sulfasalazine, talinolol, and estrone 3-sulfate, inhibited the DBF and the 5-CF transport. Contrastively, testosterone, dehydroepiandrosterone sulfate, and progesterone inhibited the DBF transport but stimulated the 5-CF transport. Natural flavonoid aglycons, such as naringenin and baicalein, also exhibited substrate-dependent effects in this manner. Conclusion: We found two fluorescein analogs, DBF and 5-CF as the OATP2B1 substrates that exhibited substrate-dependent interactions. In the experiment, the researchers used many compounds, for example, 2′,7′-Dichloro-3′,6′-dihydroxy-3H-spiro[isobenzofuran-1,9′-xanthen]-3-one (cas: 76-54-0Safety of 2′,7′-Dichloro-3′,6′-dihydroxy-3H-spiro[isobenzofuran-1,9′-xanthen]-3-one).
2′,7′-Dichloro-3′,6′-dihydroxy-3H-spiro[isobenzofuran-1,9′-xanthen]-3-one (cas: 76-54-0) belongs to benzofurans derivatives. Benzofuran derivatives are one of the most important oxygen-containing heterocycles. They are also prone to polymerisation in the presence of concentrated mineral acids and Lewis acids.Safety of 2′,7′-Dichloro-3′,6′-dihydroxy-3H-spiro[isobenzofuran-1,9′-xanthen]-3-one
Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem