Ro 20-1724 is a selective inhibitor of cAMP-specific phosphodiesterase (PDE4), with an IC50 value of 1.930μM [1]. Ro 20-1724 modulates brain cAMP utilization, thereby activating protein kinase A (PKA) and cAMP response element binding protein (CREB), and has been widely used to regulate brain function in animal models [2].
In vitro, Ro 20-1724 treatment for 2h significantly inhibited PDE4 activity in TSHR-CNG-HEK293 cells with an IC50 of 2.39μM[3]. Treatment with Ro 20-1724 at 100μM for 1 hour significantly inhibited IgE production in Peripheral blood mononuclear leukocytes (MNL) from patients with atopic dermatitis[4]. 100μM Ro 20-1724 promoted apoptosis of HL-60 cells within 5 hours[5].
In vivo, Ro 20-1724 treatment (500μg/kg/day; i.p.) for 21 days significantly attenuated streptozotocin-induced cognitive deficits and oxidative stress in rats[6]. In a mouse model of allergic asthma, oral administration of Ro 20-1724 at a dose of 3mg/kg/day for 10 days significantly reduced eosinophil influx into the lungs and reduced tumor necrosis factor-α, interleukin-4, and interleukin-5 levels in bronchoalveolar lavage fluid[7]. Intravenous infusion of Ro 20-1724 (10μg/kg/min) at a constant rate for one hour significantly attenuated endotoxin-induced changes in renal blood flow, renal vascular resistance, and glomerular filtration rate, and alleviated renal failure symptoms in rats[8].
References:
[1] Brackeen M F, Stafford J A, Cowan D J, et al. Design and synthesis of conformationally constrained analogs of 4-(3-butoxy-4-methoxybenzyl) imidazolidin-2-one (Ro 20-1724) as potent inhibitors of cAMP-specific phosphodiesterase[J]. Journal of medicinal chemistry, 1995, 38(24): 4848-4854.
[2] Kant G J, Meyerhoff J L, Lenox R H. In vivo effects of apomorphine and 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro 20–1724) on cyclic nucleotides in rat brain and pituitary[J]. Biochemical Pharmacology, 1980, 29(3): 369-373.
[3] Titus S A, Li X, Southall N, et al. A cell-based PDE4 assay in 1536-well plate format for high-throughput screening[J]. SLAS Discovery, 2008, 13(7): 609-618.
[4] Cooper K D, Kang K, Chan S C, et al. Phosphodiesterase inhibition by Ro 20-1724 reduces hyper-IgE synthesis by atopic dermatitis cells in vitro[J]. Journal of investigative dermatology, 1985, 84(6): 477-482.
[5] Zhu W H, Majluf-Cruz A, Omburo G A. Cyclic AMP-specific phosphodiesterase inhibitor rolipram and RO-20-1724 promoted apoptosis in HL60 promyelocytic leukemic cells via cyclic AMP-independent mechanism[J]. Life sciences, 1998, 63(4): 265-274.
[6] Sharma V, Bala A, Deshmukh R, et al. Neuroprotective effect of RO-20-1724-a phosphodiesterase4 inhibitor against intracerebroventricular streptozotocin induced cognitive deficit and oxidative stress in rats[J]. Pharmacology Biochemistry and Behavior, 2012, 101(2): 239-245.
[7] Clayton R A, Dick C A J, Mackenzie A, et al. The effect of selective phosphodiesterase inhibitors, alone and in combination, on a murine model of allergic asthma[J]. Respiratory research, 2004, 5(1): 4.
[8] Begany D P, Carcillo J A, Herzer W A, et al. Inhibition of type IV phosphodiesterase by Ro 20-1724 attenuates endotoxin-induced acute renal failure[J]. The Journal of pharmacology and experimental therapeutics, 1996, 278(1): 37-41.
Ro 20-1724是一种选择性cAMP特异性磷酸二酯酶（PDE4）抑制剂，IC50值为1.930μM[1]。Ro 20-1724通过调节脑内cAMP利用，激活蛋白激酶A（PKA）和cAMP反应元件结合蛋白（CREB），已广泛应用于动物模型的脑功能调控研究[2]。
在体外，Ro 20-1724处理2小时可显著抑制TSHR-CNG-HEK293细胞中的PDE4活性，IC50值为2.39μM[3]。100μM的Ro 20-1724处理特应性皮炎患者来源的外周血单核白细胞（MNL）1小时能显著抑制IgE产生[4]。100μM的Ro 20-1724处理HL-60细胞5小时内可促进细胞凋亡[5]。
在体内，大鼠每日腹腔注射Ro 20-1724（500μg/kg/day；持续21天）可显著减轻链脲佐菌素诱导的认知缺陷和氧化应激[6]。过敏性哮喘小鼠模型每日口服3mg/kg剂量的Ro 20-1724（持续10天）能显著减少肺部嗜酸性粒细胞浸润，并降低支气管肺泡灌洗液中肿瘤坏死因子-α、白细胞介素-4和白细胞介素-5水平[7]。大鼠以恒定速率静脉输注Ro 20-1724（10μg/kg/分钟，持续1小时）可显著缓解内毒素诱导的肾血流量、肾血管阻力和肾小球滤过率变化，减轻肾功能衰竭症状[8]。