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Apremilast PDE inhibitor

Name: Apremilast
SKU: S8034
Availability: InStock
Rating: 5 (8 reviews)

Cat.No.S8034

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

Chemical Structure

Molecular Weight: 460.5

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.98%

99.98

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Chemical Information, Storage & Stability

Molecular Weight	460.5	Formula	C₂₂H₂₄N₂O₇S	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	608141-41-9	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	CC-10004			Smiles	CCOC1=C(C=CC(=C1)C(CS(=O)(=O)C)N2C(=O)C3=C(C2=O)C(=CC=C3)NC(=O)C)OC

Solubility

In vitro
Batch:

DMSO : 92 mg/mL (199.78 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
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.
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.
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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	4.600mg/ml (9.99mM)	Taking the 1 mL working solution as an example, add 50 μL of 92 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	1.150mg/ml (2.50mM)	Taking the 1 mL working solution as an example, add 50 μL of 23 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
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.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	PDE4 ^[1] 74 nM TNF-α ^[1] 77 nM
In vitro	Apremilast is more potent for inhibition of PDE4 compared with cAMP or cGMP hydrolysing enzymes from other PDE families. This compound 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. It is found to inhibit the zymosan-induced PMN production of IL-8 with IC50 of 94 nM. This chemical 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. It inhibits keratinocyte TNF-αproduction, with no effect on keratinocyte cell viability as measured by intracellular ATP levels. ^[3] ^[4].
Kinase Assay	PDE4 inhibitory activity
Kinase Assay	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.
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 this compound 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 this compound in vivo, and the ED50 is determined to be 0.03 mg/kg. In another LPS-induced neutrophilia model in rats, this compound exhibited an ED50 range from 0.3 mg/kg to 0.9 mg/kg.^[1]
References	[1] https://pubmed.ncbi.nlm.nih.gov/19256507/ [2] https://pubmed.ncbi.nlm.nih.gov/9873600/ [3] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829210 [4] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911898

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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