Cilomilast (Synonyms: SB 207499)

Cell lines

MCS cell lines

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reaction Conditions

11 d; 40 μM

Applications

The results demonstrate that inhibition of PDE (Cilomilast) enhances ALP expression in MSCs via the cAMP pathway. The increase in the level of ALP activity is dependent on the dose of cilomilast. To study the effect of the inducers on MSC differentiation at similar proliferation rates, we treated MCSs, except those cultured in osteogenic medium, with 1% DMSO. We compared MSCs cultured for 11 days in the presence of different inducers with MSCs cultured in osteogenic medium in order to quantify the osteogenetic effects of the inducers. We found that the ALP activity levels of MCSs treated with a combination of PDE4 inhibitor (40 μM) and BMP-2 (300 ng/mL) were almost double the ALP activity level of MSCs treated with osteogenic medium, suggesting that the mineralisation process is more rapid.

Animal models

Female C57BL/6 mice

Dosage form

Cilomilast 0.05%; ocular surface instillation three times per day over a period of 7 days.

Applications

Real-time PCR was used to quantify the expression of transcripts encoding IL-1α, IL-1β, and TNF-α in the corneas and conjunctivae of DED-induced mice. Treatment with topical cilomilast significantly decreased the corneal expression of TNF-α as compared with the vehicle-treated group. Compared with the DED-untreated corneas, treatment with cilomilast significantly reduced IL-1α and TNF-α expression.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Munisso M C, Kang J H, Tsurufuji M, et al. Cilomilast enhances osteoblast differentiation of mesenchymal stem cells and bone formation induced by bone morphogenetic protein 2[J]. Biochimie, 2012, 94(11): 2360-2365.

[2] Sadrai Z, Stevenson W, Okanobo A, et al. PDE4 inhibition suppresses IL-17–associated immunity in dry eye disease[J]. Investigative ophthalmology & visual science, 2012, 53(7): 3584-3591.