Small molecule inhibits activity of scavenger receptor A: Lead identification and preliminary studies.-猫眼课题宝

DOI：

10.1016/j.bmcl.2015.05.090

发表时间：

2015-08-15

期刊：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

影响因子：

2.7

通讯作者：

中科院分区：

医学4区

文献类型：

作者：

Yuan, Yunyun;Li, Xia;Zaidi, Saheem A.;Arnatt, Christopher K.;Yu, Xiaofei;Guo, Chunqing;Wang, Xiang-Yang;Zhang, Yan

关键词：

Scavenger receptor A Natural product Rhein Cysteine-rich domain Homology model Cancer therapy

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494979/?report=classic

Scavenger receptor A (SRA) has been implicated in the processes of tumor invasion and acts as an immunosuppressor during therapeutic cancer vaccination. Pharmacological inhibition of SRA function thus holds a great potential to improve treatment outcome of cancer therapy. Macromolecular natural product sennoside B was recently shown to block SRA function. Here we report the identification and characterization of a small molecule SRA inhibitor rhein. Rhein, a deconstructed analogue of sennoside B, reversed the suppressive activity of SRA in dendritic cell-primed T cell activation, indicated by transcription activation of il2 gene and production of IL-2. Rhein also inhibited SRA ligand polyinosinic:polycytidylic acid (poly(I:C)) induced activation of transcriptional factors, including interferon regulatory factor 3 (IRF3) and signal transducer and activator of transcription 1 (STAT1). Additionally, this newly identified lead compound was docked into the homology models of the SRA cysteine rich domain to gain insights into its interaction with the receptor. It was then found that rhein can favorably interact with SRA cysteine rich domain. Collectively, rhein, being the first identified small molecule inhibitors for SRA, warrants further structure-activity relationship studies, which may lead to development of novel pharmacological intervention for cancer therapy.