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Piclamilast

Piclamilast用途

Piclamilast (RP 73401) 是有效的磷酸二酯酶 4 (PDE4) 的抑制剂,其在猪主动脉和可溶性嗜酸性粒细胞中的 IC50 值分别为 16 nM 和 2 nM。

Piclamilast名称

[ CAS 号 ]:
144035-83-6

[ 中文名 ]:
RP 73401

[ 英文名 ]:
Piclamilast

[英文别名 ]:

Piclamilast
Cpodpmb

Piclamilast生物活性

[ 描述 ]:

Piclamilast (RP 73401) 是有效的磷酸二酯酶 4 (PDE4) 的抑制剂,其在猪主动脉和可溶性嗜酸性粒细胞中的 IC50 值分别为 16 nM 和 2 nM。

[ 相关类别 ]:

研究领域 >> 癌症

信号通路 >> 代谢酶/蛋白酶 >> 磷酸二酯酶(PDE)

研究领域 >> 炎症/免疫

[ 靶点 ]

PDE4:16 nM (IC50, in pig aorta)

PDE4:2 nM (IC50, in eosinophil soluble)

PDE1:>100 μM (IC50)

PDE2:40 μM (IC50)

PDE3:>100 μM (IC50)

PDE5:14 μM (IC50)

[体外研究]

Piclamilast(rp73401,1μM,30min)通过涉及Ser63的AP-1激活和c-Jun磷酸化的机制显著抑制23个基因的变化[2]。Piclamilast(RP 73401)的IC50值大于100μM、40μM、>100μM、14μM,适用于PDE1、PDE2、PDE3和PDE5。分别[4]。RT-PCR[2]细胞系：人A549Ⅱ型肺上皮细胞。浓度：1μM(H2O2 200μM)。在孵育30分钟后,A549细胞的表达水平被阻止。细胞活力测定[3]细胞系：NB4细胞。浓度：30μM,培养时间：3天。结果：ATRA对NB4细胞STAT1的诱导有明显的促进作用。使表达NBT-R活性的细胞数量显著增加。

[体内研究]

吡拉米司特(rp73401,10mg/kg,30min)对白血病动物的MST无影响。吡拉米司特联合全反式维甲酸(HY-14649)在提高白血病动物的MST(40天；间隔34-45天)方面比单独使用ATRA更有效[3]。动物模型：SCID小鼠[3]。剂量：10mg/kg(联合ATRA(HY-14649))。给药：每日注射。结果：在提高白血病动物的MST(40天；间隔34-45天)方面,明显比ATRA更有效。

[参考文献]

[1]. M J Ashton, et al. Selective type IV phosphodiesterase inhibitors as antiasthmatic agents. The syntheses and biological activities of 3-(cyclopentyloxy)-4-methoxybenzamides and analogues. J Med Chem. 1994 May 27;37(11):1696-703.

[2]. Manuel Mata, et al. Piclamilast inhibits the pro-apoptotic and anti-proliferative responses of A549 cells exposed to H(2)O(2) via mechanisms involving AP-1 activation. Free Radic Res. 2012 May;46(5):690-9.

[3]. Edoardo Parrella, et al. Phosphodiesterase IV inhibition by piclamilast potentiates the cytodifferentiating action of retinoids in myeloid leukemia cells. Cross-talk between the cAMP and the retinoic acid signaling pathways. J Biol Chem . 2004 Oct 1;279(40):42026-40.

[4]. T Ukita, et al. Novel, potent, and selective phosphodiesterase-4 inhibitors as antiasthmatic agents: synthesis and biological activities of a series of 1-pyridylnaphthalene derivatives. J Med Chem. 1999 Mar 25;42(6):1088-99.

Piclamilast物理化学性质

[ 密度 ]:
1.4±0.1 g/cm3

[ 沸点 ]:
447.8±45.0 °C at 760 mmHg

[ 分子式 ]:
C₁₈H₁₈Cl₂N₂O₃

[ 分子量 ]:
381.253

[ 闪点 ]:
224.6±28.7 °C

[ 精确质量 ]:
380.069458

[ PSA ]:
63.68000

[ LogP ]:
5.25

[ 外观性状 ]:
固体

[ 蒸汽压 ]:
0.0±1.1 mmHg at 25°C

[ 折射率 ]:
1.626

[ 储存条件 ]:
2-8°C，密封，干燥

PiclamilastMSDS

详细MSDS(安全技术说明书)

Piclamilast安全信息

[ 符号 ]:

GHS07

[ 信号词 ]:
Warning

[ 危害声明 ]:
H315-H319-H335

[ 警示性声明 ]:
P261-P305 + P351 + P338

[ 危害码 (欧洲) ]:
Xi

[ 危险品运输编码 ]:
NONH for all modes of transport

Piclamilast合成路线

详细合成路线

Piclamilast上下游产品

Piclamilast上游产品

Piclamilast下游产品

Piclamilast文献

Phosphodiesterase IV inhibition by piclamilast potentiates the cytodifferentiating action of retinoids in myeloid leukemia cells. Cross-talk between the cAMP and the retinoic acid signaling pathways.

J. Biol. Chem. 279(40) , 42026-40, (2004)

Inhibition of phosphodiesterase IV by N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-methoxybenzamide (piclamilast) enhances the myeloid differentiation induced by all-trans-retinoic acid (ATRA), retin...

Potential role of phosphodiesterase 7 in human T cell function: comparative effects of two phosphodiesterase inhibitors.

Clin. Exp. Immunol. 128(3) , 460-6, (2002)

Even though the existence of phosphodiesterase (PDE) 7 in T cells has been proved, the lack of a selective PDE7 inhibitor has confounded an accurate assessment of PDE7 function in such cells. In order...

The differential impact of PDE4 subtypes in human lung fibroblasts on cytokine-induced proliferation and myofibroblast conversion.

J. Cell Physiol. 226(8) , 1970-80, (2011)

Lung fibroblast proliferation and differentiation into myofibroblasts are pathological key events during development of lung fibrosis. Cyclic nucleotide signaling is described as a negative modulator ...

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