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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H24N2O7S
Molecular Weight 460.5
Optical Activity ( + )
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of APREMILAST

SMILES

CCOC1=C(OC)C=CC(=C1)[C@@H](CS(C)(=O)=O)N2C(=O)C3=CC=CC(NC(C)=O)=C3C2=O

InChI

InChIKey=IMOZEMNVLZVGJZ-QGZVFWFLSA-N
InChI=1S/C22H24N2O7S/c1-5-31-19-11-14(9-10-18(19)30-3)17(12-32(4,28)29)24-21(26)15-7-6-8-16(23-13(2)25)20(15)22(24)27/h6-11,17H,5,12H2,1-4H3,(H,23,25)/t17-/m1/s1

HIDE SMILES / InChI

Description

Apremilast (brand name Otezla) selective inhibitor of phosphodiesterase 4 is used for the treatment of patients with moderate to severe plaque psoriasis. OTEZLA is the first and only PDE4 inhibitor approved for the treatment of plaque psoriasis, a chronic inflammatory disease of the skin resulting from an uncontrolled immune response. Apremilast also inhibits spontaneous production of TNF-alpha from human rheumatoid synovial cells. It has anti-inflammatory activity. By inhibiting PDE-4, apremilast increases intracellular levels of cAMP and thereby inhibits the production of multiple proinflammatory mediators including PDE-4, TNF-alpha, interleukin-2 (IL-2), interferon-gamma, leukotrienes, and nitric oxide synthase.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
74.0 nM [IC50]
0.074 µM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
OTEZLA
Primary
OTEZLA

Cmax

ValueDoseCo-administeredAnalytePopulation
527 ng × eq/mL
20 mg single, oral
APREMILAST, (+/-)- plasma
Homo sapiens
208 ng/mL
10 mg 2 times / day multiple, oral
APREMILAST plasma
Homo sapiens
298 ng/mL
20 mg 2 times / day multiple, oral
APREMILAST plasma
Homo sapiens
637 ng/mL
30 mg 2 times / day multiple, oral
APREMILAST plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
6632 ng × eq × h/mL
20 mg single, oral
APREMILAST, (+/-)- plasma
Homo sapiens
1008 ng × h/mL
10 mg 2 times / day multiple, oral
APREMILAST plasma
Homo sapiens
1591 ng × h/mL
20 mg 2 times / day multiple, oral
APREMILAST plasma
Homo sapiens
3467 ng × h/mL
30 mg 2 times / day multiple, oral
APREMILAST plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
50.4 h
20 mg single, oral
APREMILAST, (+/-)- plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Sample Use Guides

In Vivo Use Guide
The recommended initial dosage titration of OTEZLA (apremilast) from Day 1 to Day 5 is from 10 mg till 30 mg corresponding. Following the 5-day titration, the recommended maintenance dosage is 30 mg twice daily taken orally starting on Day 6. This titration is intended to reduce the gastrointestinal symptoms associated with initial therapy.
Route of Administration: Oral
In Vitro Use Guide
LPS-stimulated human monocytes were treated with concentrations of apremilast ranging from 6.25 nM to 100 nM.