Rational design of a highly selective UGT1A1 probe and its application in drug discovery

Detection of uridine diphosphate glucuronosyltransferase 1A1 for pancreatic cancer imaging and treatment via a “turn-on” fluorescent probe

“…13 Nilotinib was certified to be a potent inhibitor of UGT1A1 (approximately 95% inhibition). 31,41 We altered the UGT1A1 levels with chrysin and nilotinib to study the effect of the UGT1A1 level changes on Panc-1 cells. Before imaging, all experimental cells were incubated with BCy-Panc (10 μM) at 37 °C for 120 min.…”

“…29 We designed and prepared the UGT1A1 probe BCy-panc by adding ortho chloride substitution next to the phenolic hydroxyl group of benzoindocyanine, which showed extremely high substrate conversion. 31 In organisms, UGTIA1 catalyses the conjugation of glucuronic acid molecules from uridine diphosphate-glucuronide (UDPGA) to various compounds to form water-soluble glucuronic acid, which increases the water-solubility of the compounds. [37][38][39][40] In the presence of UDPGA, UGT1A1-mediated o-glucuronidation of BCy-panc can trigger the fluorescent "turn-on" switch (Scheme 1).…”

“…This finding not only provides a new optimization strategy but also provides strong support for the future development of more efficient and specific probes. 31 In other words, the probe assay is more convenient than the stable isotope peptide internal standard and liquid chromatography-tandem mass spectrometry method for absolute quantification of UGT1A1. We provide an overview of currently reported UGT1A probes in Table 1.…”

“…A "turn-on" fluorescent probe for the rapid and highly sensitive detection of UGT1A1 was prepared by adding chlorine atoms to the benzo indocyanine compound. 31,32 However, aforementioned reports only performed in vitro studies, and there is no in-depth research on in vivo experiments and specific applications of the probes. Compared with the reported probes, BCy-panc was more easily obtainable and has a higher substrate conversion.…”

Visual monitoring of biocatalytic processes using small molecular fluorescent probes: strategies-mechanisms-applications

“…This process plays an important role in the metabolic clearance of clinical drugs in vivo. [37][38][39][40] In addition, using glucosyltransferases (GTs) to achieve glycosylation has become an emerging method for industrial glycoside production. 41 Ma et al developed probe 12 for the real-time monitoring of glucoside transfer (Fig.…”