Cilomilast

SKU: orb1300763

Description

Cilomilast (SB-207499) is a selective PDE4 inhibitor with an IC50 of approximately 110 nM, exhibiting potent anti-inflammatory effects with minimal CNS penetration. It has been investigated in clinical Phase 3 trials for chronic obstructive pulmonary disease (COPD) and studied in models of inflammatory cell activation.

Research Area

Metabolism Research

Key Properties

• CAS Number: 153259-65-5
• MW: 343.42
• Purity: 99.52% (May vary between batches)
• Formula: C₂₀H₂₅NO₄
• SMILES: COc1ccc(cc1OC1CCCC1)[C@]1(CC[C@@H](CC1)C(O)=O)C#N
• Target: PDE
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:60 mg/mL (174.71 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.82 mM);Ethanol:31 mg/mL (90.27 mM)

Bioactivity

• Target IC50:
  PDE4 (human):120 nM|LPDE4:100 nM
• 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 .
• In Vitro:
  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.
• Cell Research:
  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

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

COPD, chronic, Cilomilast, disease, anti-inflammatory, Ariflo, asthma, HPDE4, obstructive, LPDE4, PDE4, immunomodulatory, Inhibitor, inhibit, phosphodiesterase, Phosphodiesterase, Phosphodiesterase (PDE), SB 207499, SB207499, SB-207499, pulmonary

Compound Identifiers

PubChem CID

151170