Home Metabolism PDE inhibitor - TNF-alpha inhibitor Apremilast For research use only.

Apremilast

Synonyms: CC-10004

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

Apremilast Chemical Structure

Apremilast Chemical Structure

CAS No. 608141-41-9

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Apremilast Related Products

Signaling Pathway

PDE Signaling Pathways

PDE Signaling Pathway

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
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].
Kinase Assay 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 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.
In Vivo
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]
Animal Research Animal Models Psoriasis mouse model
Dosages 5 mg/kg/day, divided into b.i.d.doses
Administration Oral
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06382987 Recruiting
Plaque Psoriasis
Bristol-Myers Squibb
 January 22 2024 --
NCT06122649 Recruiting
Plaque Psoriasis
Amgen
 November 27 2023 Phase 3
NCT06108544 Recruiting
Plaque Psoriasis
Takeda
 November 6 2023 Phase 3
NCT06088043 Recruiting
Plaque Psoriasis
Takeda
 November 6 2023 Phase 3
NCT05926882 Completed
Alopecia Areata
Jinnah Postgraduate Medical Centre
 August 1 2022 Phase 4
NCT04804553 Recruiting
Active Juvenile Psoriatic Arthritis
Amgen
 March 17 2022 Phase 3

Chemical Information & Solubility

Molecular Weight 460.5 Formula

C22H24N2O7S
CAS No. 608141-41-9 SDF --
Smiles CCOC1=C(C=CC(=C1)C(CS(=O)(=O)C)N2C(=O)C3=C(C2=O)C(=CC=C3)NC(=O)C)OC
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 92 mg/mL ( (199.78 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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