1094750-85-2Relevant articles and documents
Terphenyl-Based Small-Molecule Inhibitors of Programmed Cell Death-1/Programmed Death-Ligand 1 Protein-Protein Interaction
Muszak, Damian,Surmiak, Ewa,Plewka, Jacek,Magiera-Mularz, Katarzyna,Kocik-Krol, Justyna,Musielak, Bogdan,Sala, Dominik,Kitel, Radoslaw,Stec, Malgorzata,Weglarczyk, Kazimierz,Siedlar, Maciej,D?mling, Alexander,Skalniak, Lukasz,Holak, Tad A.
, p. 11614 - 11636 (2021)
We describe a new class of potent PD-L1/PD-1 inhibitors based on a terphenyl scaffold that is derived from the rigidified biphenyl-inspired structure. Using in silico docking, we designed and then experimentally demonstrated the effectiveness of the terphenyl-based scaffolds in inhibiting PD-1/PD-L1 complex formation using various biophysical and biochemical techniques. We also present a high-resolution structure of the complex of PD-L1 with one of our most potent inhibitors to identify key PD-L1/inhibitor interactions at the molecular level. In addition, we show the efficacy of our most potent inhibitors in activating the antitumor response using primary human immune cells from healthy donors.
HYDROXY FORMAMIDE DERIVATIVES AND THEIR USE
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Paragraph 0489; 0490, (2016/12/16)
Disclosed are compounds having the formula: wherein R1, R2 and R3 are as defined herein, and methods of making and using the same, including use as inhibitors of BMP1, TLL1 and/or TLL2 and in treatment of diseases associated with BMP1, TLL1 and/or TLL2 activity.
