JNJ-7777120 is a histamine H4 receptor (H4R: Ki = 4.5nM) antagonist [1]. JNJ-7777120 can inhibit the production of CCL17 and CCL22 by marrow-derived mast cells (BMMCs) under antigen stimulation, thereby reducing the inflammatory response and improving dermatitis symptoms [2]. JNJ-7777120 is primarily used to relieve inflammation and brain damage [3].
In human peripheral blood neutrophils, JNJ-7777120 (0.001, 0.01, 0.1, 1, 10μM; 30 minutes) can specifically antagonize H4 receptors and restore the degranulation function of neutrophils, verifying that H4 receptors play a negative regulatory role in inhibiting the inflammatory process [4]. In Th17 cells, the trend of cellular IL-17 secretion was inhibited after adding JNJ-7777120 (10μM; 1h) [5].
In mild traumatic brain injury (mTBI) rat model, JNJ-7777120 (1mg/kg; ip; twice/day for 7 days) treatments markedly attenuate the impairment in motor-sensory-reflex and balance functions caused by mild TBI in rats [6]. In a mouse allergic asthma model, JNJ-7777120 (20mg/kg; sc; single injection) can alleviate asthma symptoms [7]. In the LPS mouse model, JNJ-7777120 (5, 10, 20mg/kg; po; single dose) treatment reduced TNF levels [8].
References:
[1]. Thurmond RL, Desai PJ, Dunford PJ, et al. A potent and selective histamine H4 receptor antagonist with anti-inflammatory properties. The Journal of pharmacology and experimental therapeutics. 2004 Apr 1; 309(1): 404-413.
[2]. Ohsawa Y, Hirasawa N. The antagonism of histamine H 1 and H 4 receptors ameliorates chronic allergic dermatitis via anti‐pruritic and anti‐inflammatory effects in NC/N ga mice. Allergy. 2012 Aug; 67(8): 1014-1022.
[3]. Correa MF, dos Santos Fernandes JP. Targeting the Histamine H4 Receptor: Future Drugs for Inflammatory Diseases. Current Organic Chemistry. 2018 Jul 1; 22(17): 1663-1672.
[4]. Dib K, Perecko T, Jenei V, et al. The histamine H4 receptor is a potent inhibitor of adhesion-dependent degranulation in human neutrophils. Journal of Leukocyte Biology. 2014 Sep; 96(3): 411-418.
[5]. Han SH, Hur MS, Kim MJ, et al. Preliminary study of histamine H4 receptor expressed on human CD4+ T cells and its immunomodulatory potency in the IL-17 pathway of psoriasis. Journal of dermatological science. 2017 Oct 1; 88(1): 29-35.
[6]. Saglam-Cifci E, Gulec I, Sengelen A, et al. The H4R antagonist, JNJ-7777120 treatments ameliorate mild traumatic brain injury by reducing oxidative damage, inflammatory and apoptotic responses through blockage of the ERK1/2/NF-kB pathway in a rat model. Experimental Neurology. 2025 Mar 1; 385: 115133.
[7]. Beermann S, Glage S, Jonigk D, et al. Opposite effects of mepyramine on JNJ 7777120-induced amelioration of experimentally induced asthma in mice in sensitization and provocation. PloS one. 2012 Jan 17; 7(1): e30285.
[8]. Cowden JM, Yu F, Challapalli M, et al. Antagonism of the histamine H 4 receptor reduces LPS-induced TNF production in vivo. Inflammation Research. 2013 Jun; 62: 599-607.
JNJ-7777120是一种组胺H4受体（H4R：Ki = 4.5nM）拮抗剂 [1]。JNJ-7777120可以抑制骨髓来源的肥大细胞（BMMC）在抗原刺激下产生CCL17和CCL22，从而减轻炎症反应并改善皮炎症状 [2]。JNJ-7777120 主要用于缓解炎症和脑损伤 [3]。
在人外周血中性粒细胞中，JNJ-7777120（0.001、0.01、0.1、1、10μM；30分钟）可特异性拮抗H4受体，恢复中性粒细胞的脱颗粒功能，验证了H4受体在抑制炎症过程中起负调控作用 [4]。在Th17细胞中，添加JNJ-7777120（10μM；1h）后，细胞IL-17分泌趋势受到抑制 [5]。
在轻度创伤性脑损伤（mTBI）大鼠模型中，JNJ-7777120（1mg/kg；ip；每日两次，共7天）治疗显著减轻了轻度TBI对大鼠运动感觉反射和平衡功能的损害 [6]。在小鼠过敏性哮喘模型中，JNJ-7777120（20mg/kg；sc；单次注射）可以缓解哮喘症状 [7]。在LPS小鼠模型中，JNJ-7777120（5、10、20mg/kg；po；单次给药）治疗降低了TNF水平 [8]。