产品说明书

	同义名 :	AB928;A2aR/A2bR antagonist-1
	CAS号 :	2239273-34-6
	货号 :	A1193404
	分子式 :	C23H22N8O
	纯度 :	98%
	分子量 :	426.474
	MDL号 :	N/A
	存储条件：	粉末 Sealed in dry,2-8°C 液体 -20°C:3-6个月-80°C:12个月
	溶解度 :	-
	动物实验配方：

生物活性

描述

Adenosine is an endogenous modulator that triggers multiple signaling pathways through four G-protein-coupled adenosine receptors A1R, A2aR, A2bR, and A3R. A2aR and A2bR are the receptors that primarily expressly in immune cells (T cells and myeloid cells, respectively). AB928 is a dual A2aR/A2bR antagonist that inhibits A2aR and A2bR with an equilibrium binding constant of 1.4 and 2 nM, respectively[1]. In the presence of adenosine, human monocyte-derived dendritic cells differentiated and exhibited a reduced ability to stimulate IFN-γ secretion from allogenic CD4+ T-cells in a mixed lymphocyte reaction. However, the addition of AB928 reversed adenosine-mediated suppression of dendritic cell function. AB928 also rescued gene expressions regulated by adenosine during the differentiation of human monocyte-derived dendritic cells[2]. In human whole blood, AB928 at 90 nM inhibited 50% of the 5 μM 5'-N-Ethylcarboxamidoadenosine-induced phosphorylation of cAMP response element-binding protein[3]. In C57BL/6 mice inoculated with mouse mammary tumor AT3-OVA, the concurrent treatment with AB928 and chemotherapy resulted in a significant reduction in tumor volume as compared to chemotherapy alone (28 mg vs. 86 mg). Also, mice treated with both AB928 and chemotherapy exhibited increased immune cell infiltrate and stromal response in tumors. Treatment with AB928 in combination with α-PD-1 therapy also suppressed the growth of melanoma B16-F10 tumors in inoculated mice[2].

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	2.34mL 0.47mL 0.23mL	11.72mL 2.34mL 1.17mL	23.45mL 4.69mL 2.34mL

参考文献

[1]Seitz L, Jin L, Leleti M, et al. Safety, tolerability, and pharmacology of AB928, a novel dual adenosine receptor antagonist, in a randomized, phase 1 study in healthy volunteers. Invest New Drugs. 2019;37(4):711-721. [2]AB928, a dual antagonist of the A2aR and A2bR adenosine receptors, relieves adenosine-mediated immune suppression [3]Pharmacokinetic-pharmacodynamic relationship for AB928, a dual antagonist of the A2aR and A2bR adenosine receptors