Apremilast (CC-10004)

For research use only.

Catalog No.S8034

5 publications

Apremilast (CC-10004) Chemical Structure

CAS No. 608141-41-9

Apremilast (CC-10004) is a potent and orally active PDE4 and TNF-α inhibitor with IC50 of 74 nM and 77 nM, respectively.

Selleck's Apremilast (CC-10004) has been cited by 5 publications

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Biological Activity

Description Apremilast (CC-10004) is a potent and orally active PDE4 and TNF-α inhibitor with IC50 of 74 nM and 77 nM, respectively.
Targets
PDE4 [1] TNF-α [1]
74 nM 77 nM
In vitro

Apremilast is more potent for inhibition of PDE4 compared with cAMP or cGMP hydrolysing enzymes from other PDE families. Apremilast displays a broad pattern of anti-inflammatory activity in a variety of cell types, inhibits TNF-α, IL-12 and IL-23 production, as well as NK and keratinocyte responses. Apremilast is found to inhibit the zymosan-induced PMN production of IL-8 with IC50 of 94 nM. Apremilast inhibits fMLF-induced PMN CD18 and CD11b expression with IC50 of 390 nM and 74 nM, respectively, and inhibits fMLF-induced adhesion of PMN to HUVECs with IC50 of 150 nM. Apremilast inhibits keratinocyte TNF-αproduction, with no effect on keratinocyte cell viability as measured by intracellular ATP levels. [3] [4].

In vivo Apremilast is stable in the presence of human microsomes (t1/2 > 60 min). It is 90% protein bound in human plasma. Oral and intravenous administration of it in female rats showed that it have good pharmacokinetics with low clearance, a moderate volume of distribution, and a 64% oral bioavailability. In a LPS-induced TNF-αinhibition model in rats, examined the TNF-α inhibitory ability of Apremilast in vivo, and the ED50 is determined to be 0.03 mg/kg. In another LPS-induced neutrophilia model in rats, Apremilast exhibited an ED50 range from 0.3 mg/kg to 0.9 mg/kg.[1]

Protocol

Kinase Assay:[2]
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PDE4 inhibitory activity :

Cells (1×109) are washed in PBS and lysed in cold homogenization buffer (20 mM Tris-HCl, pH 7.1, 3 mM 2-mercaptoethanol, 1 mM MgCl2, 0.1 mM EGTA, 1 μM PMSF, 1 μg/mL leupeptin). Following homogenization in a Dounce homogenizer the supematant is collected by centrifugation and loaded onto a Sephacryl S-200 column equilibrated in homogenization buffer. PDE is eluted in homogenization buffer and the rolipram sensitive fractions pooled and stored in aliquots. Enzyme activity is assayed in 50 mM Tris- HCl, pH 7.5, 5 mM MgCl2 and 1 μM cAMP (of which 1% is3H cAMP) in the presence of varying concentrations of inhibitors. The amount of extract used is pre-determined to ensure that reactions are within the linear range and consumed lessthan15%of the total substrate. Reactions are performed at 30°C for 30 min and terminated by boiling for 2 min. The samples are then chilled and treated with snake 'venom (1mg/mL) at 30 °C for 15 min. Unused substrate is removed by incubation with 200 μL AG1-X8 resin for 15 min. Samples are then spun at 3000 rpm for 5 min and 50 μL of the aqueous phase taken for counting. Eachdata point is carried out in duplicate with activity expressed as percentage of control. IC50 is determined from dose response curves derived from three independent experiments.
Cell Research:[3]
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  • Cell lines: HEKn cells
  • Concentrations: ~10 μM
  • Incubation Time: 18 h
  • Method: For proliferation studies, human neonatal foreskin epidermal keratinocytes (HEKn cells) are plated at 3000 cells per well in 96-well flat bottom tissue culture plates for 2 days. HEKn cells are treated with apremilast or 0.1% DMSO as the vehicle control for 1 h before ultraviolet B (UVB) irradiation with 50 mJ/cm2 in a UV Stratalinker 2400, calibrated with 312 nm UVB bulbs. Media and compounds are replaced, and cells are incubated for 18 h. Lysates are transferred to plates and shaken for 2 min before chemiluminescence is read on a TopCount NXT Luminescence Counter.
    (Only for Reference)
Animal Research:[3]
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  • Animal Models: Psoriasis mouse model
  • Dosages: 5 mg/kg/day, divided into b.i.d.doses
  • Administration: Oral
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 92 mg/mL (199.78 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
0.5% CMC+0.25% Tween 80
For best results, use promptly after mixing.
30 mg/mL

* 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.

Chemical Information

Molecular Weight 460.5
Formula

C22H24N2O7S

CAS No. 608141-41-9
Storage powder
in solvent
Synonyms N/A
Smiles CCOC1=C(C=CC(=C1)C(CS(=O)(=O)C)N2C(=O)C3=C(C2=O)C(=CC=C3)NC(=O)C)OC

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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% DMSO % % Tween 80 % ddH2O
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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04528082 Not yet recruiting Drug: Apremilast|Drug: Placebo Behçet Disease Amgen January 20 2022 Phase 3
NCT04804553 Not yet recruiting Drug: Apremilast|Drug: Placebo Active Juvenile Psoriatic Arthritis Amgen September 27 2021 Phase 3
NCT04175613 Recruiting Drug: Apremilast Psoriasis Amgen December 20 2019 Phase 3
NCT03836885 Withdrawn Drug: Apremilast|Drug: Placebo Oral Lichen Planus Sunnybrook Health Sciences Centre|Celgene|Sunnybrook Research Institute November 21 2019 Phase 2
NCT03656666 Recruiting Drug: Apremilast|Drug: Placebo Lichen Planus of Vulva|Female Genital Disease Oslo University Hospital|Celgene Corporation|Amgen September 24 2019 Phase 2

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PDE Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID