Cilomilast 是选择性的、口服具有活性的磷酸二酯酶 4 抑制剂。 它对 PDE4 的选择性高于 PDE1，PDE2，PDE3 和 PDE5 (IC50=74，65，>100，83 μM)。它具有抗炎和免疫调节功能，可用于研究哮喘和慢性阻塞性肺疾病。

Cilomilast is a potent PDE4 inhibitor with IC50 of about 110 nM, has anti-inflammatory activity and low central nervous system activity. Phase 3.

Cilomilast produces a concentration-dependent increase in cAMP content in U937 cells. Cilomilast produces a concentration-dependent increase in cAMP content in U937 cells. [2] In isolated human monocytes, Cilomilast and (R)-rolipram are equipotent at suppressing LPS-induced TNF-α formation with -log (IC50) of 7.0 and 7.2, respectively. Both Cilomilast and (R)-rolipram produces a modest prevention of fMLP-induced degranulation of human neutrophils. Cilomilast and (R)-rolipram are equipotent at suppressing neutrophil activation with -log (IC50) of 7.1 and 6.4, respectively. [2] Cilomilast significantly decreases the expression of TNF-α in the cornea and IL-1α, IL-1β, and TNF-α in the conjunctivaas compared to vehicle control. Cilomilast treatment markedly decreases the presence of CD11b+ antigen-presenting cells in the central and peripheral cornea, and leads to decreased conjunctival expression of cytokines IL-6, IL-23, and IL-17. Moreover, Cilomilast decreases the expression of IL-17 and IL-23 in the draining lymph nodes. [3] Cilomilast reduces TLR4 expression, IL-8 release and neutrophil chemotactic activity as well as it increased IP-10 release and lymphocyte chemotactic activity. [4]

Cilomilast inhibits human TNFα production with oral ED50 of 4.9 mg/kg. In contrast to their equipotent activity against TNFα production, Cilomilast (ED50 = 2.3 mg/kg, p.o.) is 10-fold less potent than R-rolipram (ED50 = 0.23 mg/kg, p.o.) in reversing reserpine-induced hypothermia, a model of antidepressant activity. [1] In time course studies, Cilomilast (30 mg/kg, p.o.) suppresses TNFα production for at least 10 hour. The ability of Cilomilast to modulate interleukin-4 productionin vivo is assessed in a chronic oxazolone-induced contact sensitivity model in Balb/c mice. Topical administration of Cilomilast (1000 μg) inhibits intralesional concentrations of interleukin-4. [1] Orally administered cilomilast dose-dependently inhibits production of interleukin-4, TNF-α, and cysteinyl leukotrienes, as well as leukocyte infiltration in bronchoalveolar lavage fluid from the airways of ovalbumin-sensitized Brown Norway rats [5].

U937 cells (1-2 × 10 6) are incubated at 37 °C in a shaking water bath with Cilomilast for 1 min before the addition of 0.1 μM PGE2 (total volume of 200 μL). The incubation proceeds for an additional 4 min and is stopped by the addition of 0.1 mL of HClO4 (17.5%), neutralized with 0.15 ml of K2

153259-65-5

C20H25NO4

343.423

Ariflo;SB-207499;西洛司特

DMSO:64 mg/mL (186.4 mM)
H2O:<1 mgml
Ethanol:31 mg/mL(90.3 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years