Song, Zilan; Liu, Bo; Peng, Xia; Gu, Wangting; Sun, Yiming; Xing, Li; Xu, Yi; Geng, Meiyu; Ai, Jing; Zhang, Ao published the artcile< Design, Synthesis, and Pharmacological Evaluation of Biaryl-Containing PD-1/PD-L1 Interaction Inhibitors Bearing a Unique Difluoromethyleneoxy Linkage>, Related Products of 5505-63-5, the main research area is difluoromethyleneoxy linkage PD1 PDL1 interaction inhibitor anticancer.
Blockade of immune checkpoint PD-1/PD-L1 has been a promising anticancer strategy; however, clin. available PD-1/PD-L1 small-mol. inhibitors are lacking. In view of the high potency of compound 2 (BMS-1002), structural fine tuning of the methoxy linkage together with diverse modification in the solvent interaction region was conducted. A series of novel derivatives featuring a difluoromethyleneoxy linkage were designed. Compound 43 was identified as the most promising PD-1/PD-L1 inhibitor with an IC50 value of 10.2 nM in the HTRF assay. This compound is capable of promoting CD8+ T cell activation through inhibiting PD-1/PD-L1 cellular signaling. Moreover, in the Hepa1-6 syngeneic mouse model, administration of compound 43 at 1 mg/kg dosage promoted CD8+ T cell activation and delayed the tumor growth with good tolerance. Notably, the tumor in one mouse of the compound 43-treated group was completely regressed. These results indicate that compound 43 is a promising candidate worthy of further investigation.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 5505-63-5 belongs to class alcohols-buliding-blocks, and the molecular formula is C6H14ClNO5, Related Products of 5505-63-5.
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