18333-80-7Relevant articles and documents
A theranostic probe of indoleamine 2,3-dioxygenase 1 (IDO1) for small molecule cancer immunotherapy
Wu, Ying,Zhang, Yanhui,Chen, Xi,Hu, Yulu,Dong, Guoqiang,Guo, Yuan,Sheng, Chunquan
, (2021)
Discovering novel small molecules for cancer immunotherapy represents a promising but challenging strategy in future cancer treatment. Herein, we designed the first theranostic fluorescent probes to efficiently detect and inhibit the enzymatic activity of
Identification and Characterization of a Single High-Affinity Fatty Acid Binding Site in Human Serum Albumin
Wenskowsky, Lea,Schreuder, Herman,Derdau, Volker,Matter, Hans,Volkmar, Julia,Nazaré, Marc,Opatz, Till,Petry, Stefan
, p. 1044 - 1048 (2018)
A single high-affinity fatty acid binding site in the important human transport protein serum albumin (HSA) is identified and characterized using an NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl)-C12 fatty acid. This ligand exhibits a 1:1 binding stoichiometry in its HSA complex with high site-specificity. The complex dissociation constant is determined by titration experiments as well as radioactive equilibrium dialysis. Competition experiments with the known HSA-binding drugs warfarin and ibuprofen confirm the new binding site to be different from Sudlow-sites I and II. These binding studies are extended to other albumin binders and fatty acid derivatives. Furthermore an X-ray crystal structure allows locating the binding site in HSA subdomain IIA. The knowledge about this novel HSA site will be important for drug depot development and for understanding drug-protein interaction, which are important prerequisites for modulation of drug pharmacokinetics.
Discovery of EGFR-Targeted Environment-Sensitive fluorescent probes for cell imaging and efficient tumor detection
Sheng, Jun,Sun, Xiu-Li,Wang, Li-Xia,Wang, Xuan-Jun,Wang, Ze-Hao,Zi, Cheng-Ting
, (2022/02/21)
Overexpression of human epidermal growth factor receptor (EGFR) plays an important role in several signaling pathways inside and outside the cell, especially in the processes of cell proliferation, differentiation, and death in various cancers. Due to the complexity of the structure and function of EGFR, research on the fluorescence visualization of EGFR protein visualization has proved challenging. One possible strategy for designing a receptor-targeting fluorescent probe with a switching mechanism is to introduce an environment-sensitive fluorophore into the drug ligand. Based on this strategic molecular design, we introduced two environment-sensitive small molecular fluorophores, dansyl chloride (DNS) and nitrobenzoxadiazole (NBD), to replace the morpholine group of gefitinib, achieving a series of fluorescent molecular probes bearing a switching mechanism. The GN probes exhibited prominent environment sensitivity, suggesting good performance as turn-on EGFR-targeting fluorescent ligands. The representative probe GN3 specifically responded to tumor cells overexpressing EGFR, which was validated with live-cell fluorescence imaging and in vivo xenograft tumor imaging. Ligand-induced EGFR phosphorylation in A431 cells was considerably inhibited by probe GN3, demonstrating that this probe still functions as an EGFR inhibitor. Owing to the turn-on response of GN3 to EGFR in tumor cells, and the competitive replacement behavior to the EGFR inhibitor gefitinib, these probes have the potential to be used for fluorescence imaging of cells overexpressing EGFR.
