Cilomilast

Catalog No.S1455 Batch:S145502

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Technical Data

Formula

C20H25NO4
Molecular Weight 343.42 CAS No. 153259-65-5
Solubility (25°C)* In vitro DMSO 69 mg/mL (200.92 mM)
Ethanol 50 mg/mL (145.59 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Cilomilast (SB-207499) is a potent PDE4 inhibitor with IC50 of about 110 nM, has anti-inflammatory activity and low central nervous system activity. Phase 3.
Targets
LPDE4 [1]
(Cell-free assay)		 HPDE4 [1]
(Cell-free assay)
100 nM 120 nM
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. [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]
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. [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].
Features Cilomilast has been used to treat chronic obstructive pulmonary disease (COPD) for many years.

Protocol (from reference)

Cell Assay:[2]
  • Cell lines

    U937 cells

  • Concentrations

    0.1-10 μM

  • Incubation Time

    5 min

  • Method

    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.
Animal Study:[1]
  • Animal Models

    Balb/c, CD-1 and C57B1/6 male mice weighing from 18 to 25 g with human monocytes or endotoxin-induced shock

  • Dosages

    3, 6, 12, 25, 50 mg/kg

  • Administration

    Gavage

References

  • https://pubmed.ncbi.nlm.nih.gov/9808700/
  • https://pubmed.ncbi.nlm.nih.gov/9435206/
  • https://pubmed.ncbi.nlm.nih.gov/22577075/
  • https://pubmed.ncbi.nlm.nih.gov/21382614/
  • https://pubmed.ncbi.nlm.nih.gov/21315169/

Customer Product Validation

LNCaP-C4 prostate cancer cells were suspended in matrigel and transplanted under the kidney capsule of male nude mice hosts. Mice were treated with vehicle-only (10% EtOH, 90% olive oil) control, cilomilast or NVP-ABE171 by gavage (n=7-11 for each respective group)The xenografts LNCaP-C4 xenografts were excised, fixed in formalin, and embedded in paraffin blocks. IHC with Ki67 (proliferation), TUNEL (apoptosis), or p21 (senescence) was performed. Representative Ki67 and TUNEL photomicrographs for cilomilast and NVP-ABE171 treatment group are shown.

Data from [ Mol Cancer Res , 2014 , 10.1158/1541-7786.MCR-14-0110 ]

<p> </p><div>ALP activity levels relative to control: (a) samples treated with 300 ng/mL of BMP-2; (b) samples treated with 30 ng/mL of BMP-2. Cells cultured with 1% DMSO for 11 days were used as control cells. Bar represent mean  SD for 8 experiments. PDE4 I =PDE4 inhibitor, SM =standard medium, OM =osteogenic medium.</div>

Data from [ Biochimie , 2012 , 94, 2360e2365 ]

<p> </p><div>ALP activity levels relative to samples treated with DMSO. Cells cultured with</div><div>1% DMSO for 11 days were used as control cells. The inset shows a schematic representation of the PDE4 inhibitor (PDE4 I) and H89 pathways. PDE4 I blocks the</div><div>degradation of the intracellular cAMP signalling by PDE, and increases the PKA levels. By the use of an efficient PKA inhibitor, H89, the pathway activated downstream by PKA is completely blocked. Bar represent mean  SD for 8 experiments.</div>

Data from [ Biochimie , 2012 , 94, 2360e2365 ]

Phosphodiesterase (PDE) 4 inhibitors increase formoterol-induced cAMP and MKP-1 mRNA expression. Growth-arrested ASM cells were pretreated for 30 minutes with the PDE4 inhibitors cilomilast (A and B, 0.1-10 μM). The impact of PDE4 inhibition was assessed by: (A) measuring cAMP production in response to stimulation with 10 nM formoterol for 15 minutes in comparison to vehicle (results expressed as percentage of formoterol-induced cAMP); and (B) measuring MKP-1 mRNA expression by RT-PCR in response to stimulation with 10 nM formoterol for 1 hour in comparison to vehicle (results expressed as percentage of formoterol-induced MKP-1). Statistical analysis was performed using one-way ANOVA then Fisher’s post hoc multiple comparison test. *Significant increase (P < 0.05). Data are mean ± SEM values from n = 7 primary ASM cell cultures.

Data from [ , , Am J Respir Cell Mol Biol, 2015, 52(5):634-40 ]

Selleck's Cilomilast Has Been Cited by 9 Publications

Aberrant TCF21 upregulation in adenomyosis impairs endometrial decidualization by increasing PDE4C expression [ Biochim Biophys Acta Mol Basis Dis, 2025, 1871(1):167526] PubMed: 39326465
Inhibition of PDE4/PDE4B improves renal function and ameliorates inflammation in cisplatin-induced acute kidney injury. [ Am J Physiol Renal Physiol, 2020, 318(3):F576-F588] PubMed: 31961716
A multi-targeted liquid chromatography–mass spectrometryscreening procedure for the detection in human urine of drugsnon-prohibited in sport commonly used by the athletes [Mazzarino M, et al. J Pharm Biomed Anal, 2016, 117:47-60] PubMed: 26342446
Inhibitors of Phosphodiesterase 4, but Not Phosphodiesterase 3, Increase β2-Agonist–Induced Expression of Antiinflammatory Mitogen-Activated Protein Kinase Phosphatase 1 in Airway Smooth Muscle Cells [Patel BS Am J Respir Cell Mol Biol, 2015, 52(5):634-40] PubMed: 25296132
Phosphodiesterase 4D inhibitors limit prostate cancer growth potential [ Mol Cancer Res, 2015, 13(1):149-60] PubMed: 25149359
Phosphodiesterase 4D Inhibitors Limit Prostate Cancer Growth Potential [Powers GL, et al. Mol Cancer Res, 2015, 13(1):149-60]
Inhibitors of Phosphodiesterase 4, but Not Phosphodiesterase 3, Increase b2-Agonist–Induced Expression of Antiinflammatory Mitogen-Activated Protein Kinase Phosphatase 1 in Airway Smooth Muscle Cells [Patel BS, et al. AM J Resp Cell Mol, 2014, 10.1165/rcmb.2014-0344OC]
Monitoring phosphodiesterase‐4 inhibitors using liquid chromatography/(tandem) mass spectrometry in sports drug testing [Thevis M Rapid Commun Mass Spectrom, 2013, 27(9):993-1004] PubMed: 23592202
Cilomilast enhances osteoblast differentiation of mesenchymal stem cells and bone formation induced by bone morphogenetic protein 2. [Munisso MC, et al. Biochimie, 2012, 94(11):2360-5] PubMed: 22706281

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Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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