Recommanded Product: 5-(Chloromethyl)nicotinonitrile. The reaction of aromatic heterocyclic molecules with protons is called protonation. Aromatic heterocycles are more basic than benzene due to the participation of heteroatoms. Compound: 5-(Chloromethyl)nicotinonitrile, is researched, Molecular C7H5ClN2, CAS is 562074-59-3, about Symmetry-based ligand design and evaluation of small molecule inhibitors of programmed cell death-1/programmed death-ligand 1 interaction. Author is Kawashita, Seiji; Aoyagi, Koichi; Yamanaka, Hiroshi; Hantani, Rie; Naruoka, Shiori; Tanimoto, Atsuo; Hori, Yuji; Toyonaga, Yukiyo; Fukushima, Kyoko; Miyazaki, Susumu; Hantani, Yoshiji.
The development of small mol. inhibitors of PD-1/PD-L1 is eagerly anticipated for treatment of cancer. We focused on the symmetry of the ternary complex structure of reported small mol. ligands and hPD-L1 homodimers, and designed partially- or fully-sym. compounds for more potent inhibitors. The design of the new compounds was guided by our hypothesis that the designed sym. compound would induce a flip of sidechain of ATyr56 protein residue to form a new cavity. The designed compound 4 exhibited substantially increased binding affinity to hPD-L1, as well as PD-1/PD-L1 inhibitory activity in physiol. conditions. Compound 4 also showed a dose-dependent increase in IFN-γ secretion levels in a mixed lymphocyte reaction assay. These results not only indicate the feasibility of targeting the PD-1/PD-L1 pathway with small mols., but illustrate the applicability of the symmetry-based ligand design as an attractive methodol. for targeting protein-protein interaction stabilizers.
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1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics