Formula: C8H6BrNIn 2021 ,《Synthesis and pharmacological evaluation of novel resorcinol biphenyl ether analogs as small molecule inhibitors of PD-1/PD-L1 with benign toxicity profiles for cancer treatment》 appeared in Biochemical Pharmacology (Amsterdam, Netherlands). The author of the article were Cao, Hao; Cheng, Binbin; Liu, Ting; Chen, Jianjun. The article conveys some information:
Programmed death protein 1 (PD-1)/programmed death protein ligand 1 (PD-L1) pathway is one of the most actively pursued targets in cancer immunotherapy. In a continuation of authors research interest in this pathway, synthesized and evaluated the pharmacol. activities of a series of resorcinol biphenyl ether analogs as small mol. PD-1/PD-L1 inhibitors for cancer treatment. Among the 27 newly synthesized compounds, I was found to have the highest inhibitory effect against PD-1/PDL-1 with an IC50 value of 56.58 nM in the HTRF (homogeneous time-resolved fluorescence) assay. In addition, I dose-dependently promoted HepG2 cell death in a co-culture model of HepG2/hPD-L1 and Jurkat T cells. Furthermore, mol. modeling study indicated that I binds with high affinity to the binding interface of PD-L1. Moreover, I effectively inhibited tumor growth (TGI of 76.4% at 90 mg/kg) in an immune checkpoint humanized mouse model with no obvious toxicity. Finally, I did not cause in vivo cardiotoxicity and bone marrow suppression (myelosuppression) to BALB/c mice. Taken together, these results suggest that I deserves further investigation as a potent and safe PD-1/PDL-1 inhibitor for cancer treatment. In the part of experimental materials, we found many familiar compounds, such as 4-Cyanobenzyl bromide(cas: 17201-43-3Formula: C8H6BrN)
4-Cyanobenzyl bromide(cas: 17201-43-3) can reacts with 2H-tetrazole in the presence of KOH to yield 4-[(2H-tetra-zol-2-yl)methyl]benzonitrile. And it may be used in the synthesis of ligands containing a chelating pyrazolyl-pyridine group with a pendant aromatic nitrile.Formula: C8H6BrN
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts