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Details

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

SHOW SMILES / InChI
Structure of APREMILAST

SMILES

CCOC1=CC(=CC=C1OC)[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
Molecular Formula C22H24N2O7S
Molecular Weight 460.5
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

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

2014
86
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
7468
Psoriasis
 74.0 nM [IC50]
Inhibitor
7468
 0.074 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phosphodiesterase 4
Approved
7883
OTEZLA
Primary
Phosphodiesterase 4
Approved
7883
OTEZLA
Approved (off-label)
8
PubMed

PubMed

TitleDatePubMed
The effects of selective cytokine inhibitory drugs (CC-10004 and CC-1088) on VEGF and IL-6 expression and apoptosis in myeloma and endothelial cell co-cultures.
2004 Feb
CC-10004 .
2005 May
Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor.
2009 Mar 26
Disposition, metabolism and mass balance of [(14)C]apremilast following oral administration.
2011 Dec
Novel systemic drugs under investigation for the treatment of psoriasis.
2012 Jul
Novel systemic drugs for psoriasis: mechanism of action for apremilast, a specific inhibitor of PDE4.
2013 Jun
Apremilast: a PDE4 inhibitor for the treatment of psoriatic arthritis.
2015 May
Patents

Patents

20030187052
1
20050192336
1
20050267196
1
20060183787
1
20060183788
1

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.
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:45:10 UTC 2019
Edited
by admin
on Mon Oct 21 20:45:10 UTC 2019
Record UNII
UP7QBP99PN
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
APREMILAST
DASH   INN   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
CC-10004
Code English
APREMILAST [INN]
Common Name English
APREMILAST [WHO-DD]
Common Name English
(+)-N-(2-((1S)-1-(3-ETHOXY-4-METHOXYPHENYL)-2-(METHYLSULFONYL)ETHYL)-1,3-DIOXO- 2,3-DIHYDRO-1H-ISOINDOL-4-YL)ACETAMIDE
Systematic Name English
APREMILAST [USAN]
Common Name English
APREMILAST [MI]
Common Name English
APREMILAST [VANDF]
Common Name English
OTEZLA
Brand Name English
ACETAMIDE, N-(2-((1S)-1-(3-ETHOXY-4-METHOXYPHENYL)-2-(METHYLSULFONYL)ETHYL)-2,3-DIHYDRO-1,3-DIOXO-1H-ISOINDOL-4-YL)-
Systematic Name English
APREMILAST [JAN]
Common Name English
CC10004
Code English
Classification Tree Code System Code
NDF-RT N0000182961
Created by admin on Mon Oct 21 20:45:10 UTC 2019 , Edited by admin on Mon Oct 21 20:45:10 UTC 2019
WHO-ATC L04AA32
Created by admin on Mon Oct 21 20:45:10 UTC 2019 , Edited by admin on Mon Oct 21 20:45:10 UTC 2019
EMA ASSESSMENT REPORTS OTEZLA (AUTHORIZED: ARTHRITIS, PSORIATIC)
Created by admin on Mon Oct 21 20:45:10 UTC 2019 , Edited by admin on Mon Oct 21 20:45:10 UTC 2019
NCI_THESAURUS C744
Created by admin on Mon Oct 21 20:45:10 UTC 2019 , Edited by admin on Mon Oct 21 20:45:10 UTC 2019
EU-Orphan Drug EU/3/13/1180
Created by admin on Mon Oct 21 20:45:10 UTC 2019 , Edited by admin on Mon Oct 21 20:45:10 UTC 2019
WHO-VATC QL04AA32
Created by admin on Mon Oct 21 20:45:10 UTC 2019 , Edited by admin on Mon Oct 21 20:45:10 UTC 2019
Code System Code Type Description
IUPHAR
7372
Created by admin on Mon Oct 21 20:45:10 UTC 2019 , Edited by admin on Mon Oct 21 20:45:10 UTC 2019
PRIMARY
NDF-RT
N0000182960
Created by admin on Mon Oct 21 20:45:10 UTC 2019 , Edited by admin on Mon Oct 21 20:45:10 UTC 2019
PRIMARY Phosphodiesterase 4 Inhibitors [MoA]
INN
8872
Created by admin on Mon Oct 21 20:45:10 UTC 2019 , Edited by admin on Mon Oct 21 20:45:10 UTC 2019
PRIMARY
HSDB
608141-41-9
Created by admin on Mon Oct 21 20:45:10 UTC 2019 , Edited by admin on Mon Oct 21 20:45:10 UTC 2019
PRIMARY
MERCK INDEX
M2010
Created by admin on Mon Oct 21 20:45:10 UTC 2019 , Edited by admin on Mon Oct 21 20:45:10 UTC 2019
PRIMARY Merck Index
MESH
C505730
Created by admin on Mon Oct 21 20:45:10 UTC 2019 , Edited by admin on Mon Oct 21 20:45:10 UTC 2019
PRIMARY
PUBCHEM
11561674
Created by admin on Mon Oct 21 20:45:10 UTC 2019 , Edited by admin on Mon Oct 21 20:45:10 UTC 2019
PRIMARY
EVMPD
SUB130837
Created by admin on Mon Oct 21 20:45:10 UTC 2019 , Edited by admin on Mon Oct 21 20:45:10 UTC 2019
PRIMARY
ChEMBL
CHEMBL514800
Created by admin on Mon Oct 21 20:45:10 UTC 2019 , Edited by admin on Mon Oct 21 20:45:10 UTC 2019
PRIMARY
RXCUI
1492727
Created by admin on Mon Oct 21 20:45:10 UTC 2019 , Edited by admin on Mon Oct 21 20:45:10 UTC 2019
PRIMARY RxNorm
CAS
608141-41-9
Created by admin on Mon Oct 21 20:45:10 UTC 2019 , Edited by admin on Mon Oct 21 20:45:10 UTC 2019
PRIMARY
NCI_THESAURUS
C147044
Created by admin on Mon Oct 21 20:45:10 UTC 2019 , Edited by admin on Mon Oct 21 20:45:10 UTC 2019
PRIMARY
Related Record Type Details
Structure of APREMILAST
EXCRETED UNCHANGED
URINE
CAMP-SPECIFIC 3',5'-CYCLIC PHOSPHODIESTERASE PDE4B1
TARGET -> INHIBITOR
IC50
CAMP-SPECIFIC 3',5'-CYCLIC PHOSPHODIESTERASE HPDE4D2
TARGET -> INHIBITOR
IC50
CAMP-SPECIFIC 3',5'-CYCLIC PHOSPHODIESTERASE PDE4C1
TARGET -> INHIBITOR
IC50
CAMP-SPECIFIC 3',5'-CYCLIC PHOSPHODIESTERASE PDE4B2
TARGET -> INHIBITOR
IC50
CAMP-SPECIFIC 3',5'-CYCLIC PHOSPHODIESTERASE PDE4A1
TARGET -> INHIBITOR
Apremilast is a selective inhibitor of PDE4 that regulates inflammatory mediators.
COMPETITIVE INHIBITOR
IC50
TUMOR NECROSIS FACTOR-.ALPHA. HUMAN (PLASMA DERIVED, SOLUBLE FORM)
TARGET -> INHIBITOR
INHIBITS PDE4 AND INCREASES cAMP CONCENTRATION
INDIRECT
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
Related Record Type Details
Structure of N-DEACETYL-N-HYDROXYACETYL APREMILAST-O-GLUCURONIDE
METABOLITE -> PARENT
MINOR
PLASMA; URINE
Structure of N-DEACETYL APREMILAST
METABOLITE -> PARENT
Metabolites M7 and M17,which were present at trace levels in plasma, did retain some PDE4 and TNF-.alpha. inhibition activity, with IC 50 values similar to those of apremilast.
FECAL
Structure of O-DEMETHYL APREMILAST GLUCURONIDE
METABOLITE INACTIVE -> PARENT
MAJOR
PLASMA; URINE
Structure of 3-ACETAMIDOPHTHALIC ACID
METABOLITE -> PARENT
MINOR
FECAL
Structure of O-DEMETHYL-N-DEACETYL APREMILAST
METABOLITE -> PARENT
MINOR
FECAL
Structure of O-DEMETHYL-N-DEACETYL-N-HYDROXYACETYL APREMILAST
METABOLITE -> PARENT
MINOR
FECAL
Structure of N-DEACETYL-N-HYDROXYACETYL APREMILAST
METABOLITE -> PARENT
Metabolites M7 and M17,which were present at trace levels in plasma, did retain some PDE4 and TNF-.alpha. inhibition activity, with IC 50 values similar to those of apremilast.
FECAL; URINE
Structure of 2-(ACETYLAMINO)-6-((((1S)-1-(3-ETHOXY-4-HYDROXYPHENYL)-2-(METHYLSULFONYL)ETHYL)AMINO)CARBONYL)BENZOIC ACID
METABOLITE -> PARENT
Major fecal
MAJOR
FECAL
Structure of O-DEETHYL APREMILAST-O-GLUCURONIDE
METABOLITE -> PARENT
MINOR
PLASMA; URINE
Structure of O-DEMETHYL APREMILAST GLUCURONIDE
METABOLITE INACTIVE -> PARENT
Structure of 4-((1S)-1-((3-(ACETYLAMINO)-2-CARBOXYBENZOYL)AMINO)-2-(METHYLSULFONYL)ETHYL)-2-ETHOXYPHENYL-.BETA.-D-GLUCOPYRANOSIDURONIC ACID
METABOLITE -> PARENT
MINOR
URINE
Structure of 3-(2-HYDROXYACETAMIDO)PHTHALIC ACID
METABOLITE -> PARENT
MINOR
FECAL
Structure of O-DEMETHYL-N-DEACETYL APREMILAST-O-GLUCURONIDE
METABOLITE -> PARENT
MINOR
PLASMA; URINE
Structure of O-DEMETHYL APREMILAST
METABOLITE -> PARENT
MINOR
FECAL
Related Record Type Details
Structure of APREMILAST
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
NIH
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