Piclamilast

Names

[ Name ]:
Piclamilast

[Synonym ]:
3-(cyclopentyloxy)-N-(3,5-dichloro-4-pyridyl)-4-methoxybenzamide
3-cyclopentyloxy-N-(3,5-dichloropyridin-4-yl)-4-methoxybenzamide
Piclamilast
3-(Cyclopentyloxy)-N-(3,5-dichloro-4-pyridinyl)-4-methoxybenzamide
Cpodpmb
Benzamide, 3-(cyclopentyloxy)-N-(3,5-dichloro-4-pyridinyl)-4-methoxy-
3-(Cyclopentyloxy)-N-(3,5-dichloropyridin-4-yl)-4-methoxybenzamide

Biological Activity

[Description]:

Piclamilast (RP 73401) is a phosphodiesterase 4 (PDE4) inhibitor, with IC50 values of 16 nM and 2 nM in pig aorta and eosinophil soluble, respectively[1][2][3][4].

[Related Catalog]:

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> Phosphodiesterase (PDE)

Research Areas >> Inflammation/Immunology

[Target]

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)

[In Vitro]

Piclamilast (RP 73401, 1 μM, 30 min) significantly inhibits the changes in 23 genes via mechanisms involving AP-1 activation and c-Jun phosphorylation at Ser63[2]. Piclamilast (RP 73401) exhibits IC50 values >100 μM, 40 μM, >100 μM, 14 μM for PDE1, PDE2, PDE3 and PDE5. Respectively[4]. RT-PCR[2] Cell Line: Human A549 type II lung epithelial cells. Concentration: 1 μM (H2O2 200 μM). Incubation Time: 30 min. Result: Prevented H2O2 -induced changes in gene expression levels in A549 cells. Cell Viability Assay[3] Cell Line: NB4 cells. Concentration: 30 μM. Incubation Time: 3 days. Result: Exerted a significant enhancing effect on the induction of STAT1 observed in ATRA-treated NB4 cells. Caused a significant increase in the number of cells expressing NBT-R activity.

[In Vivo]

Piclamilast (RP 73401, 10 mg/kg, 30 min) alone does not affect the MST of leukemia-bearing animals. Piclamilast combined with ATRA (HY-14649) significantly more effective than ATRA alone in increasing the MST (40 days; interval 34–45 days) of leukemia-bearing animals[3]. Animal Model: SCID mice[3]. Dosage: 10 mg/kg (combined with ATRA (HY-14649)). Administration: Injection daily. Result: Significantly more effective than ATRA alone in increasing the MST (40 days; interval 34–45 days) of leukemia-bearing animals.

[References]

[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.

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
447.8±45.0 °C at 760 mmHg

[ Molecular Formula ]:
C₁₈H₁₈Cl₂N₂O₃

[ Molecular Weight ]:
381.253

[ Flash Point ]:
224.6±28.7 °C

[ Exact Mass ]:
380.069458

[ PSA ]:
63.68000

[ LogP ]:
5.25

[ Vapour Pressure ]:
0.0±1.1 mmHg at 25°C

[ Index of Refraction ]:
1.626

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Hazard Codes ]:
Xi

[ RIDADR ]:
NONH for all modes of transport

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

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 ...