一种强效小分子免疫调节剂的免疫活性和转录组分析

Yasser Tabana , Shima Shahbaz , Dinesh Babu , Marawan Ahmed , Tae Chul Moon , Frederick G. West , Richard Fahlman , Arno G. Siraki , Shokrollah Elahi , Khaled Barakat
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引用次数: 0

摘要

在免疫疗法中使用小分子药物是一个前景广阔、发展迅速的领域,有可能彻底改变我们治疗各种免疫疾病的方法。在免疫疗法中使用小分子药物的成功案例有很多,例如检查点抑制剂,它们在治疗多种肿瘤方面取得了重大成功。然而,尽管取得了这些成功,用于免疫疗法的小分子药物的开发仍处于起步阶段,还有许多挑战有待解决。在最近的一项研究中,我们实验室报道了一种小分子(化合物 A)的免疫刺激作用(A)。在本文中,我们研究了该分子的衍生物(化合物 B)(图 1B),并分析了其理化性质、免疫活性和转录组图谱。化合物 B 具有可接受的代谢稳定性,对 PBMC 无毒性。我们还证明化合物 B 能够通过诱导促炎细胞因子和促进 T 细胞增殖来调节免疫系统。RNAseq 结果显示,化合物 B 能够显著上调参与刺激免疫反应通路的基因。我们的研究结果表明,化合物 B 可以作为一种很有前景的治疗药物来调节免疫系统。目前正在对其免疫活性的分子靶点进行鉴定和验证。
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The immunological activities and transcriptome analysis of a potent small-molecule immunomodulator

The use of small molecules in immunotherapy is a promising and rapidly growing field with the potential to revolutionize the way we treat a wide range of immunological diseases. The success stories of using small molecules in immunotherapy have been highlighted with many drugs, such as checkpoint inhibitors, which have achieved significant success in treating several types of tumors. However, despite this success, the development of small molecules for immunotherapy is still in its infancy, and there are many challenges that remain to be addressed. In a recent study, our laboratory reported the immunostimulatory effect of a small molecule (Compound A) (A). In this paper, we studied a derivative of this molecule (Compound B) (Fig. 1B). and analysed its physiochemical properties, immunological activities, and transcriptome profiling. Compound B exhibited acceptable metabolic stability and no toxicity against PBMCs. We also demonstrated that Compound B was capable of modulating the immune system by inducing pro-inflammatory cytokines and promoting T-cell proliferation. RNAseq results showed that Compound B was able to significantly upregulate genes involved in stimulating the immune response pathways. Our findings suggest that Compound B may serve as a promising therapeutic agent to modulate the immune system. The identification and validation of the molecular targets responsible for its immunological activities are underway.

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来源期刊
Medicine in Drug Discovery
Medicine in Drug Discovery Medicine-Pharmacology (medical)
CiteScore
8.30
自引率
0.00%
发文量
30
审稿时长
21 days
期刊介绍:
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