131088-02-3Relevant articles and documents
Fluorescently Labeled Amino Acids as Building Blocks for Bioactive Molecules
H?u?ler, Daniela,Gütschow, Michael
, p. 245 - 255 (2016)
A series of twelve fluorescently labeled amino acids were designed by assembling different coumarin, fluorescein, or nitrobenzo-furazan fluorophores with N-protected lysine or 2-aminopropionic acid. The synthesized amino acids were evaluated with regard to their spectroscopic properties. The easy introduction of the amino acids into peptides and peptidomimetics was exemplarily shown for one coumarin-labeled- amino acid.
Synthesis of 5,6-dihydro-4H-benzo[d]isoxazol-7-one and 5,6-dihydro-4H-isoxazolo[5,4-c]pyridin-7-one Derivatives as Potential Hsp90 Inhibitors
Musso, Loana,Cincinelli, Raffaella,Giannini, Giuseppe,Manetti, Fabrizio,Dallavalle, Sabrina
, p. 1030 - 1035 (2015)
A novel class of 5,6-dihydro-4H-benzo[d]isoxazol-7-ones and 5,6-dihydro-4H-isoxazolo[5,4-c]pyridin-7-ones was designed, synthesized, and assayed to investigate the affinity toward Hsp90 protein. The synthetic route was based on a 1,3-dipolar cycloaddition of nitriloxides, generated in situ from suitable benzaldoximes, with 2-bromocyclohex-2-enones or 3-bromo-5,6-dihydro-1H-pyridin-2-ones. Whereas all the compounds bearing a benzamide group on the bicyclic scaffold were devoid of activity, the derivatives carrying a resorcinol-like fragment showed a remarkable inhibitory effect on Hsp90. Docking calculations were performed to investigate the orientation of the new compounds within the binding site of the enzyme. A series of 5,6-dihydro-4H-benzo[d]isoxazol-7-ones and 5,6-dihydro-4H-isoxazolo[5,4-c]pyridin-7-ones was designed, synthesized, and assayed to investigate affinity toward Hsp90 protein. Compounds carrying a resorcinol-like fragment showed a remarkable inhibitory effect on Hsp90. Docking calculations were performed to investigate the orientation of the new compounds within the binding site of the enzyme.
One-step radiosynthesis and initial evaluation of a small molecule PET tracer for PD-L1 imaging
Miao, Yinxing,Lv, Gaochao,Chen, Yinfei,Qiu, Ling,Xie, Minhao,Lin, Jianguo
, (2020)
Programmed cell death protein-ligand 1 (PD-L1) is a crucial biomarker in immunotherapy and its expression level plays a key role in the guidance of anti-PD-L1 therapy. It had been reported that PD-L1 was quantified by noninvasive imaging with more developed radiotracers. In our study, a novel [18F]fluoride labeled small molecule inhibitor, [18F]LN was designed for positron emission tomography (PET) imaging in both PD-L1 transfected (A375-hPD-L1) and non-transfected (A375) melanoma-bearing mice. LN showed the specificity (IC50 = 50.39 ± 2.65 nM) to PD-L1 confirmed by competitive combination and cell flow cytometry (FACS) analysis. The radiotracer [18F]LN was obtained via 18F-19F isotope exchange from precursor LN. After radiosynthesis, [18F]LN was achieved with a high radiochemical purity (RCP) above 95% and got a favorable molar activity of 36.34 ± 5.73 GBq/μmol. [18F]LN displayed the moderate affinity (Kd = 65.27 ± 3.47 nM) to PD-L1 by specific binding assay. And it showed 1.3-fold higher uptake in A375-hPD-L1 cells than that in A375 cells. PET imaging revealed that [18F]LN could enter into PD-L1 expressing tumor site and visualize the outline of tumor. And tumor uptake (1.96 ± 0.27 %ID/g) reached the maximum at 15 min in the positive group, showed 2.2-fold higher than the negative (0.89 ± 0.31 %ID/g) or the blocked (1.07 ± 0.26 %ID/g) groups. Meanwhile, biodistribution could slightly distinguish the positive from the negative. The results indicated [18F]LN would become an efficient tool for evaluating PD-L1 expression with further optimization.
Programmed death ligand-1 targeted compound as well as preparation method and application thereof
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Paragraph 0079-0082; 0085-0086, (2021/08/19)
The invention discloses a programmed death ligand-1 targeted compound. The invention also discloses a preparation method and an application of the compound. According to the compound disclosed by the invention, FDG containing polyhydroxy is introduced, so that the polarity is increased, the water solubility is also enhanced, and the compound also has the characteristics of good stability and relatively high molar activity. When the compound disclosed by the invention is applied to a PET imaging agent, the compound can quickly reach a tumor part, the relative uptake value of a tumor is increased, the imaging target-to-cost ratio is enhanced, the imaging time window is prolonged, the preparation process is simple, the compound has a great prospect in targeted probe development, the image contrast can be optimized, the in-vivo distribution can be improved, and the compound can be widely applied to medical research.
Design, synthesis and biological evaluation of isoxazole-containing biphenyl derivatives as small-molecule inhibitors targeting the programmed cell death-1/ programmed cell death-ligand 1 immune checkpoint
Wang, Lixun,Yang, Yifei,Zhang, Huibin,Zhang, Jian,Zhou, Jinpei,Zhu, Peiyu
, (2021/04/05)
Monoclonal antibodies targeting the programmed cell death-1/ programmed cell death-ligand 1 (PD-1/PD-L1) immune checkpoint have achieved enormous success in cancer immunotherapy. But the antibody-based immunotherapies carry a number of unavoidable deficie
