Piclamilast

Biological Activity

Piclamilast (RP 73401) is a selective PDE4 inhibitor with IC50 of 1 nM at PDE4 from human neutrophils. Inhibition of PDE4 blocks hydrolysis of cAMP thereby increasing levels of cAMP within cells. cAMP suppresses the activity of immune and inflammatory cells. Piclamilast also inhibits LTB4 synthesis in human neutrophils with IC50 of 2 nM. PDE4 inhibitor Piclamilast (RP 73401) displays >19,000-fold selectivity over other PDE isoenzymes. It is comparable to other PDE4 inhibitors for its anti-inflammatory effects. Piclamilast pre-treatment significantly inhibited the changes in 23 genes via mechanisms involving AP-1 activation and c-Jun phosphorylation at Ser63.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information

References

Piclamilast inhibits the pro-apoptotic and anti-proliferative responses of A549 cells exposed to H(2)O(2) via mechanisms involving AP-1 activation.
Mata M, et al. Free Radic Res. 2012 May;46(5):690-9. PMID: 22360706.