product name Cilomilast
Description: Cilomilast (also known as Ariflo, SB-207,499) is a potent and orally active PDE4 inhibitor with IC50 of about 110 nM, it has anti-inflammatory activity and low central nervous system activity. Cilomilast was developed for the treatment of respiratory disorders such as asthma and Chronic Obstructive Pulmonary Disease (COPD). Clinical trial results showed reasonable efficacy for treating COPD, but side effects were problematic and it is unclear whether cilomalast will be marketed, or merely used in the development of newer drugs. Cilomilast is a second-generation PDE4 inhibitor with antiinflammatory effects that target bronchoconstriction, mucus hypersecretion, and airway remodeling associated with COPD.
References: J Pharmacol Exp Ther. 1998 Nov;287(2):705-11; Int Immunopharmacol. 2011 Jun;11(6):732-9.
343.42
Formula
C20H25NO4
CAS No.
153259-65-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 69 mg/mL (200.9 mM)
Water: <1 mg/mL
Ethanol: 50 mg/mL (145.6 mM)
Solubility (In vivo)
5% DMSO+95% Corn oil: 30 mg/mL
Synonyms
SB-207499
other peoduct :
| In Vitro |
In vitro activity: Cilomilast produces a concentration-dependent increase in cAMP content in U937 cells. Cilomilast produces a concentration-dependent increase in cAMP content in U937 cells. 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. 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. Cilomilast reduces TLR4 expression, IL-8 release and neutrophil chemotactic activity as well as it increased IP-10 release and lymphocyte chemotactic activity. Kinase Assay: Cell Assay: 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 K23 (1.0 M) and diluted to 1 mL with sodium acetate buffer. Samples are centrifuged at 3000 × g for 10 min. Aliquots of the supernatant fraction are assayed for cAMP content by radioimmunoassay using commercially available kits. |
|---|---|
| In Vivo | 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. 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. 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. |
| Animal model | Balb/c, CD-1 and C57B1/6 male mice weighing from 18 to 25 g with human monocytes or endotoxin-induced shock |
| Formulation & Dosage | Dissovled in Olive oil; 3, 6, 12, 25, 50 mg/kg; oral gavage |
| References | J Pharmacol Exp Ther. 1998 Nov;287(2):705-11; Int Immunopharmacol. 2011 Jun;11(6):732-9. |
