Subtle Structural Changes across the Boundary between A2AR/A2BR Dual Antagonism and A2BR Antagonism: A Novel Class of 2-Aminopyrimidine-Based Derivatives

Wang, Haojie; Yang, Xinyu; Li, Yan; Ze, Shuyin; Feng, Bo; Weng, Yuan; Gao, Aoqi; Song, Gaojie; Liu, Mingyao; Xie, Qiong; Wang, Yonghui; Lu, Weiqiang

doi:10.1021/acs.jmedchem.4c00250

Cited by 1 publication

(1 citation statement)

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“…A 2A R is one of the potential drug targets in immuno-oncology. The expression of A 2A R in TME is much higher than in nonmalignant tissues . High expression of A 2A R in TME is correlated with shorter overall survival (OS), higher stage, and poor prognosis. ,, Clinical trials or preclinical studies of A 2A R blockade suggested that individuals with high AR expression characteristics were more likely to benefit from adenosine blockade therapy.…”

Section: Discussionmentioning

confidence: 99%

Development of Preladenant-Based Radiotracers for Imaging A_2AR in Tumors

Zeng,

Liu,

Huang

et al. 2024

J. Med. Chem.

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Activation of the adenosine 2A receptor (A 2A R) can lead to tumor immunosuppression, which results in poor prognosis of immunotherapy. The aim of this study was to design novel 18 Flabeled probes ([ 18 F]F-PFP 2 and [ 18 F]F-PFP 4 ) to visualize A 2A R in the tumor. The uptake of radioprobes in A 2A R-negative 4T1 breast tumor was lower than that of A 2A R-positive B16F10 melanoma at 1 h p.i. (1.22 ± 0.36% ID/g vs 2.80 ± 0.72% ID/g), 2 h p.i. (1.09 ± 0.20% ID/g vs 2.93 ± 0.76% ID/g) and 3 h p.i. (0.89 ± 0.27% ID/ g vs 2.73 ± 0.58% ID/g), respectively. B16F10 lung metastasis models were employed to expand the application scenarios, observing significantly higher uptake of [ 18 F]F-PFP 2 in metastatic lesions compared to normal lung tissue (5.55 ± 2.18% ID/g vs 1.89 ± 0.65% ID/g, tumor/lung ratio ∼3). It is given that [ 18 F]F-PFP 2 might lay the foundation for establishing an A 2A R-targeted imaging evaluation system for tumors, which will provide more precise guidance for personalized treatment.

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