5-BDBD is a potent and selective P2X4 receptor antagonist with an IC50 value of 0.5-0.75µM, capable of inhibiting rP2X4R-mediated currents[1-2]. 5-BDBD can alleviate asthma symptoms and has potential for treating alcoholic fatty liver disease[3-4].
In vitro, treatment of prostate cancer cells (DU145 cells) with 5-BDBD (5 or 10µM) for 24 to 72 hours significantly inhibited their migration and invasion capabilities and induced the expression of the apoptosis marker cleaved caspase-3[5]. Treatment of primary rat osteoblasts with 5-BDBD (0.1-10µM) for 14 days dose-dependently inhibited bone nodule formation and reduced alkaline phosphatase activity[6].
In vivo, continuous administration of 5-BDBD (1.0mM; via an implanted osmotic pump at a flow rate of 1.0µL/h for 3 days) to adult male Sprague-Dawley rats subjected to cortical contusion injury (CCI) significantly suppressed the activation of microglia in the ipsilateral cortex and hippocampus and reduced Iba-1 protein expression levels. 5-BDBD also significantly decreased the levels of pro-inflammatory cytokines in the ipsilateral cortex and hippocampus[7]. Treatment of 8-12-week-old wild-type mice subjected to 60 minutes of middle cerebral artery occlusion (MCAo) with 5-BDBD (1mg/kg; administered orally daily for 3 days) significantly reduced infarct volume and neurological deficit scores at 3 days after stroke, and decreased the levels of the pro-inflammatory cytokine IL-1β and blood-brain barrier permeability[8].
References:
[1] Long T, He W, Pan Q, et al. Microglia P2X4 receptor contributes to central sensitization following recurrent nitroglycerin stimulation. J Neuroinflammation. 2018 Aug 30;15(1):245.
[2] Coddou C, Sandoval R, Hevia MJ, et al. Characterization of the antagonist actions of 5-BDBD at the rat P2X4 receptor. Neurosci Lett. 2019 Jan 18;690:219-224.
[3] Hu B, Feng X, Wang L, et al. 5-BDBD ameliorates an OVA-induced allergic asthma by the reduction of Th2 cytokines production. Iran J Basic Med Sci. 2018 Apr;21(4):364-369.
[4] Xia GQ, Cai JN, Wu X, et al. The mechanism by which ATP regulates alcoholic steatohepatitis through P2X4 and CD39. Eur J Pharmacol. 2022 Feb 5;916:174729.
[5] Maynard JP, Lu J, Vidal I, et al. P2X4 purinergic receptors offer a therapeutic target for aggressive prostate cancer. J Pathol. 2022 Feb;256(2):149-163.
[6] Orriss IR, Davies BK, Bourne LE, et al. Modulation of osteoblast differentiation and function by the P2X4 receptor. Purinergic Signal. 2023 Jun;19(2):367-378.
[7] Kobayashi M, Moro N, Yoshino A, et al. Inhibition of P2X4 and P2X7 receptors improves histological and behavioral outcomes after experimental traumatic brain injury in rats. Exp Ther Med. 2023 Jun 23;26(2):378.
[8] Srivastava P, Cronin CG, Scranton VL, et al. Neuroprotective and neuro-rehabilitative effects of acute purinergic receptor P2X4 (P2X4R) blockade after ischemic stroke. Exp Neurol. 2020 Jul;329:113308.
5-BDBD是一种有效的选择性P2X4受体拮抗剂，IC50值为0.5-0.75µM，能够抑制rP2X4R介导的电流[1-2]。5-BDBD能够缓解哮喘症状，且具有治疗酒精性脂肪肝的潜力[3-4]。
在体外，5-BDBD（5或10μM）处理前列腺癌细胞（DU145细胞）24至72小时，显著抑制其迁移和侵袭能力，并诱导凋亡标志物cleaved caspase-3的表达[5]。5-BDBD（0.1-10μM）处理原代大鼠成骨细胞14天，剂量依赖性地抑制骨结节形，并降低碱性磷酸酶活性[6]。
在体内，5-BDBD（1.0mM；通过植入的渗透泵以1.0μL/h流速连续给药3天）处理遭受皮质挫伤（CCI）的成年雄性Sprague-Dawley大鼠，显著抑制损伤同侧皮层和海马区小胶质细胞的激活，并降低Iba-1蛋白表达水平，还显著降低损伤同侧皮层和海马区促炎细胞因子的水平[7]。5-BDBD（1mg/kg；每日口服；持续3天）处理经历60分钟大脑中动脉闭塞（MCAo）的8-12周龄野生型小鼠，在卒中后3天显著降低梗死体积和神经功能缺损评分，并减少促炎细胞因子IL-1β的水平和血脑屏障通透性[8]。