U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Molecular Formula C22H24N2O7S
Molecular Weight 460.5
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including http://ir.celgene.com/releasedetail.cfm?releaseid=872240; http://www.ncbi.nlm.nih.gov/pubmed/26806620; http://www.ncbi.nlm.nih.gov/pubmed/?term=20525198; http://www.ncbi.nlm.nih.gov/pubmed/20050849

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
494
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 74.0 nM [IC50]
Inhibitor
8297
 0.074 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
OTEZLA

Approved Use

For the treatment of adult patients with active psoriatic arthritis and patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy

Launch Date

2014
Primary
Approved
8429
OTEZLA

Approved Use

For the treatment of adult patients with active psoriatic arthritis and patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy

Launch Date

2014
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
527 ng × eq/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/21859393/
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
APREMILAST, (+/-)- plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
208 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/22748702/
10 mg 2 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
APREMILAST plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
298 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/22748702/
20 mg 2 times / day multiple, oral
dose: 20 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
APREMILAST plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
637 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/22748702/
30 mg 2 times / day multiple, oral
dose: 30 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
APREMILAST plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
6632 ng × eq × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/21859393/
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
APREMILAST, (+/-)- plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1008 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/22748702/
10 mg 2 times / day multiple, oral
dose: 10 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
APREMILAST plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1591 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/22748702/
20 mg 2 times / day multiple, oral
dose: 20 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
APREMILAST plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3467 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/22748702/
30 mg 2 times / day multiple, oral
dose: 30 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
APREMILAST plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
50.4 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/21859393/
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
APREMILAST, (+/-)- plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
50 mg 2 times / day steady, oral
Overdose
Dose: 50 mg, 2 times / day
Route: oral
Route: steady
Dose: 50 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
https://pubmed.ncbi.nlm.nih.gov/27285466
healthy, adult
n = 8
Health Status: healthy
Age Group: adult
Population Size: 8
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
https://pubmed.ncbi.nlm.nih.gov/27285466
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
https://pubmed.ncbi.nlm.nih.gov/27285466
30 mg 2 times / day steady, oral
Recommended
Dose: 30 mg, 2 times / day
Route: oral
Route: steady
Dose: 30 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Disc. AE: Nausea, Diarrhea...
AEs leading to
discontinuation/dose reduction:
Nausea (3%)
Diarrhea (2%)
Headache (2%)
Dizziness (1%)
Vomiting (1%)
Fatigue (1%)
Migraine (<1%)
Abdominal pain upper (<1%)
Decreased appetite (<1%)
Depressed mood (<1%)
Abdominal distension (<1%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
20 mg 2 times / day steady, oral
Dose: 20 mg, 2 times / day
Route: oral
Route: steady
Dose: 20 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Disc. AE: Nausea, Diarrhea...
AEs leading to
discontinuation/dose reduction:
Nausea (1%)
Diarrhea (1%)
Vomiting (<1%)
Fatigue (<1%)
Migraine (<1%)
Abdominal pain upper (<1%)
Decreased appetite (<1%)
Depressed mood (<1%)
Depression (<1%)
Abdominal distension (<1%)
Dyspepsia (<1%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
AEs

AEs

AESignificanceDosePopulation
Dizziness 1%
Disc. AE
30 mg 2 times / day steady, oral
Recommended
Dose: 30 mg, 2 times / day
Route: oral
Route: steady
Dose: 30 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Fatigue 1%
Disc. AE
30 mg 2 times / day steady, oral
Recommended
Dose: 30 mg, 2 times / day
Route: oral
Route: steady
Dose: 30 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Vomiting 1%
Disc. AE
30 mg 2 times / day steady, oral
Recommended
Dose: 30 mg, 2 times / day
Route: oral
Route: steady
Dose: 30 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Diarrhea 2%
Disc. AE
30 mg 2 times / day steady, oral
Recommended
Dose: 30 mg, 2 times / day
Route: oral
Route: steady
Dose: 30 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Headache 2%
Disc. AE
30 mg 2 times / day steady, oral
Recommended
Dose: 30 mg, 2 times / day
Route: oral
Route: steady
Dose: 30 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Nausea 3%
Disc. AE
30 mg 2 times / day steady, oral
Recommended
Dose: 30 mg, 2 times / day
Route: oral
Route: steady
Dose: 30 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Abdominal distension <1%
Disc. AE
30 mg 2 times / day steady, oral
Recommended
Dose: 30 mg, 2 times / day
Route: oral
Route: steady
Dose: 30 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Abdominal pain upper <1%
Disc. AE
30 mg 2 times / day steady, oral
Recommended
Dose: 30 mg, 2 times / day
Route: oral
Route: steady
Dose: 30 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Decreased appetite <1%
Disc. AE
30 mg 2 times / day steady, oral
Recommended
Dose: 30 mg, 2 times / day
Route: oral
Route: steady
Dose: 30 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Depressed mood <1%
Disc. AE
30 mg 2 times / day steady, oral
Recommended
Dose: 30 mg, 2 times / day
Route: oral
Route: steady
Dose: 30 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Migraine <1%
Disc. AE
30 mg 2 times / day steady, oral
Recommended
Dose: 30 mg, 2 times / day
Route: oral
Route: steady
Dose: 30 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Diarrhea 1%
Disc. AE
20 mg 2 times / day steady, oral
Dose: 20 mg, 2 times / day
Route: oral
Route: steady
Dose: 20 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Nausea 1%
Disc. AE
20 mg 2 times / day steady, oral
Dose: 20 mg, 2 times / day
Route: oral
Route: steady
Dose: 20 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Abdominal distension <1%
Disc. AE
20 mg 2 times / day steady, oral
Dose: 20 mg, 2 times / day
Route: oral
Route: steady
Dose: 20 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Abdominal pain upper <1%
Disc. AE
20 mg 2 times / day steady, oral
Dose: 20 mg, 2 times / day
Route: oral
Route: steady
Dose: 20 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Decreased appetite <1%
Disc. AE
20 mg 2 times / day steady, oral
Dose: 20 mg, 2 times / day
Route: oral
Route: steady
Dose: 20 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Depressed mood <1%
Disc. AE
20 mg 2 times / day steady, oral
Dose: 20 mg, 2 times / day
Route: oral
Route: steady
Dose: 20 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Depression <1%
Disc. AE
20 mg 2 times / day steady, oral
Dose: 20 mg, 2 times / day
Route: oral
Route: steady
Dose: 20 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Dyspepsia <1%
Disc. AE
20 mg 2 times / day steady, oral
Dose: 20 mg, 2 times / day
Route: oral
Route: steady
Dose: 20 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Fatigue <1%
Disc. AE
20 mg 2 times / day steady, oral
Dose: 20 mg, 2 times / day
Route: oral
Route: steady
Dose: 20 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Migraine <1%
Disc. AE
20 mg 2 times / day steady, oral
Dose: 20 mg, 2 times / day
Route: oral
Route: steady
Dose: 20 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Vomiting <1%
Disc. AE
20 mg 2 times / day steady, oral
Dose: 20 mg, 2 times / day
Route: oral
Route: steady
Dose: 20 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
unhealthy
n = 501
Health Status: unhealthy
Sex: M+F
Population Size: 501
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s000MedR.pdf
Page: p. 61
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737

inducer
781
inducer
389

substrate
1037
substrate
1217
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
BCRP
699

OAT1
599

OAT3
642

OCT2
647

OATP1B1
788

OATP1B3
706

MRP2
383

MRP3
157

MRP4
204

P-gp
1461
CYP1A2
1054

CYP2A6
543

P-gp
1537

BCRP
561

OAT1
326

OAT3
339

OCT2
355

OATP1B1
406

OATP1B3
350

CYP2C8
693

CYP2C19
991

CYP2E1
667
CYP1A2
701

CYP2C19
293

CYP2B6
547
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
1692
 no
CYP2C19
1553
 no
CYP2C9
1819
 no
BCRP
773
 weak [IC50 >10 uM]
MRP2
475
 weak [IC50 >10 uM]
MRP3
207
 weak [IC50 >10 uM]
MRP4
238
 weak [IC50 >10 uM]
OAT1
603
 weak [IC50 >10 uM]
OAT3
644
 weak [IC50 >10 uM]
OATP1B1
803
 weak [IC50 >10 uM]
OATP1B3
715
 weak [IC50 >10 uM]
OCT2
648
 weak [IC50 >10 uM]
P-gp
1650
 weak [IC50 >10 uM]
CYP2B6
1001
 weak
CYP3A4
1925
 weak
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP3A4
1737
 major
BCRP
561
 no
CYP2C9
1037
 no
CYP2E1
667
 no
OAT1
326
 no
OAT3
339
 no
OATP1B1
406
 no
OATP1B3
350
 no
OCT2
355
 no
CYP2C19
991
 weak
CYP2C8
693
 weak
CYP2D6
1217
 weak
CYP1A2
1054
 yes
CYP2A6
543
 yes
P-gp
1537
 yes
no (co-administration study)
Comment: in vivo bioavailability is more than 70% and DDI study with ketoconazole (CYP3A and P-gp inhibitor) did not reveal the potential of a significant interaction
Page: 5.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:78540
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:78540
ChemicalBook
CB12563430
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB12563430
MolPort
MolPort-023-219-158
https://www.molport.com/shop/molecule-link/MolPort-023-219-158
Selleck Chemicals
apremilast-cc-10004
http://www.selleckchem.com/products/apremilast-cc-10004.html
ZINC
ZINC000030691736
http://zinc15.docking.org/substances/ZINC000030691736
PubMed

PubMed

TitleDatePubMed
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
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on Fri Dec 15 15:56:23 GMT 2023
Edited
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on Fri Dec 15 15:56:23 GMT 2023
Record UNII
UP7QBP99PN
Record Status Validated (UNII)
Record Version
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Name Type Language
APREMILAST
DASH   INN   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
CC-10004
Code English
Apremilast [WHO-DD]
Common Name English
apremilast [INN]
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
N-[2-[(1S)-1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]acetamide
Systematic Name English
APREMILAST [MI]
Common Name English
APREMILAST [VANDF]
Common Name English
OTEZLA
Brand Name English
APREMILAST [ORANGE BOOK]
Common 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 Fri Dec 15 15:56:23 GMT 2023 , Edited by admin on Fri Dec 15 15:56:23 GMT 2023
WHO-ATC L04AA32
Created by admin on Fri Dec 15 15:56:23 GMT 2023 , Edited by admin on Fri Dec 15 15:56:23 GMT 2023
EMA ASSESSMENT REPORTS OTEZLA (AUTHORIZED: ARTHRITIS, PSORIATIC)
Created by admin on Fri Dec 15 15:56:23 GMT 2023 , Edited by admin on Fri Dec 15 15:56:23 GMT 2023
NCI_THESAURUS C744
Created by admin on Fri Dec 15 15:56:23 GMT 2023 , Edited by admin on Fri Dec 15 15:56:23 GMT 2023
EU-Orphan Drug EU/3/13/1180
Created by admin on Fri Dec 15 15:56:23 GMT 2023 , Edited by admin on Fri Dec 15 15:56:23 GMT 2023
WHO-VATC QL04AA32
Created by admin on Fri Dec 15 15:56:23 GMT 2023 , Edited by admin on Fri Dec 15 15:56:23 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID30976289
Created by admin on Fri Dec 15 15:56:23 GMT 2023 , Edited by admin on Fri Dec 15 15:56:23 GMT 2023
PRIMARY
USAN
SS-114
Created by admin on Fri Dec 15 15:56:23 GMT 2023 , Edited by admin on Fri Dec 15 15:56:23 GMT 2023
PRIMARY
IUPHAR
7372
Created by admin on Fri Dec 15 15:56:23 GMT 2023 , Edited by admin on Fri Dec 15 15:56:23 GMT 2023
PRIMARY
NDF-RT
N0000182960
Created by admin on Fri Dec 15 15:56:23 GMT 2023 , Edited by admin on Fri Dec 15 15:56:23 GMT 2023
PRIMARY Phosphodiesterase 4 Inhibitors [MoA]
INN
8872
Created by admin on Fri Dec 15 15:56:23 GMT 2023 , Edited by admin on Fri Dec 15 15:56:23 GMT 2023
PRIMARY
HSDB
8221
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PRIMARY
MERCK INDEX
m2010
Created by admin on Fri Dec 15 15:56:23 GMT 2023 , Edited by admin on Fri Dec 15 15:56:23 GMT 2023
PRIMARY Merck Index
MESH
C505730
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PRIMARY
PUBCHEM
11561674
Created by admin on Fri Dec 15 15:56:23 GMT 2023 , Edited by admin on Fri Dec 15 15:56:23 GMT 2023
PRIMARY
LACTMED
Apremilast
Created by admin on Fri Dec 15 15:56:23 GMT 2023 , Edited by admin on Fri Dec 15 15:56:23 GMT 2023
PRIMARY
EVMPD
SUB130837
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PRIMARY
ChEMBL
CHEMBL514800
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PRIMARY
RXCUI
1492727
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PRIMARY RxNorm
CHEBI
78540
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PRIMARY
CAS
608141-41-9
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PRIMARY
DRUG BANK
DB05676
Created by admin on Fri Dec 15 15:56:23 GMT 2023 , Edited by admin on Fri Dec 15 15:56:23 GMT 2023
PRIMARY
FDA UNII
UP7QBP99PN
Created by admin on Fri Dec 15 15:56:23 GMT 2023 , Edited by admin on Fri Dec 15 15:56:23 GMT 2023
PRIMARY
DAILYMED
UP7QBP99PN
Created by admin on Fri Dec 15 15:56:23 GMT 2023 , Edited by admin on Fri Dec 15 15:56:23 GMT 2023
PRIMARY
SMS_ID
100000156798
Created by admin on Fri Dec 15 15:56:23 GMT 2023 , Edited by admin on Fri Dec 15 15:56:23 GMT 2023
PRIMARY
DRUG CENTRAL
4829
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PRIMARY
NCI_THESAURUS
C147044
Created by admin on Fri Dec 15 15:56:23 GMT 2023 , Edited by admin on Fri Dec 15 15:56:23 GMT 2023
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 PDE4D2
TARGET -> INHIBITOR
IC50
CAMP-SPECIFIC 3',5'-CYCLIC PHOSPHODIESTERASE PDE4C1
TARGET -> INHIBITOR
IC50
CAMP-SPECIFIC 3',5'-CYCLIC PHOSPHODIESTERASE PDE4B2
TARGET -> INHIBITOR
IC50
Structure of APREMILAST, (±)-
RACEMATE -> ENANTIOMER
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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