Target Information

Target General Information

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Target ID

T47941 (Former ID: TTDC00170)

Target Name

Phosphodiesterase 4 (PDE4)

Synonyms

PDE-4

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Gene Name

NO-GeName

Target Type

Successful target

[1]

Disease

[+] 5 Target-related Diseases

Asthma [ICD-11: CA23]

Atopic eczema [ICD-11: EA80]

Castlemans disease [ICD-11: 4B2Y]

Cough [ICD-11: MD12]

Psoriasis [ICD-11: EA90]

Function

Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes||Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents

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BioChemical Class

Phosphoric diester hydrolase

UniProt ID

NOUNIPROTAC

Drugs and Modes of Action

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Approved Drug(s)

[+] 5 Approved Drugs

Apremilast

Drug Info

Approved

Psoriasis vulgaris

[2], [3]

crisaborole

Drug Info

Approved

Atopic dermatitis

[4]

Ibudilast

Drug Info

Approved

Castleman's disease

[5]

Oxtriphylline

Drug Info

Approved

Cough

[6]

Roflumilast

Drug Info

Approved

Asthma

[7], [8]

Clinical Trial Drug(s)

[+] 11 Clinical Trial Drugs

Arofylline

Drug Info

Phase 3

Chronic obstructive pulmonary disease

[9]

ARQ-151

Drug Info

Phase 3

Atopic dermatitis

[10]

ARQ-154

Drug Info

Phase 2

Plaque psoriasis

[11]

ASP9831

Drug Info

Phase 2

Steatohepatitis

[12]

E6005

Drug Info

Phase 2

Atopic dermatitis

[13]

IC-485

Drug Info

Phase 2

Chronic obstructive pulmonary disease

[9]

LEO-32731

Drug Info

Phase 2

Plaque psoriasis

[14]

ONO-6126

Drug Info

Phase 2

Chronic obstructive pulmonary disease

[9]

PF-07038124

Drug Info

Phase 2

Atopic dermatitis

[15]

SUN13834

Drug Info

Phase 2

Gram-positive bacterial infection

[16]

TAK-648

Drug Info

Phase 1

Type 2 diabetes

[17]

Discontinued Drug(s)

[+] 3 Discontinued Drugs

Cilomilast

Drug Info

Discontinued in Phase 3

Chronic obstructive pulmonary disease

[18], [19]

GW842470X

Drug Info

Discontinued in Phase 2

Atopic dermatitis

[20]

Ro 20-1724

Drug Info

Terminated

Asthma

[21], [22]

Mode of Action

[+] 2 Modes of Action

Inhibitor

[+] 20 Inhibitor drugs

Apremilast

Drug Info

[1], [3], [23]

Ibudilast

Drug Info

[5]

Arofylline

Drug Info

[9]

ARQ-151

Drug Info

[26]

ARQ-154

Drug Info

[27]

ASP9831

Drug Info

[28]

E6005

Drug Info

[29]

IC-485

Drug Info

[9]

LEO-32731

Drug Info

[14]

ONO-6126

Drug Info

[9]

PF-07038124

Drug Info

[30]

SUN13834

Drug Info

[31]

TAK-648

Drug Info

[32]

Cilomilast

Drug Info

[9]

GW842470X

Drug Info

[20]

Ro 20-1724

Drug Info

[33]

(R)-Rolipram

Drug Info

[34], [35]

(S)-Rolipram

Drug Info

[34], [35]

Iso-caffeine

Drug Info

[31]

S-(-)-enantiomer of 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP)

Drug Info

[31]

Modulator

[+] 5 Modulator drugs

crisaborole

Drug Info

[4]

Oxtriphylline

Drug Info

[24]

Roflumilast

Drug Info

[8], [25]

CT-5357

Drug Info

[36]

SDZ-PDI-747

Drug Info

[36]

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

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Co-Targets

Co-Targets Info

Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

Top

REF 1

Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis. Inflamm Allergy Drug Targets. 2007 Mar;6(1):17-26.

REF 2

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7372).

REF 3

Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.

REF 4

2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76.

REF 5

Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond. Nat Rev Drug Discov. 2019 Oct;18(10):770-796.

REF 6

FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 086742.

REF 7

REF 8

2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.

REF 9

Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.

REF 10

ClinicalTrials.gov (NCT04804605) Open Label Extension Trial of PDE4 Inhibition With Roflumilast for the Management of Atopic Dermatitis (INTEGUMENT-OLE). U.S. National Institutes of Health.

REF 11

ClinicalTrials.gov (NCT04128007) Safety and Efficacy of ARQ-154 Foam in Adolescent and Adult Subjects With Scalp and Body Psoriasis. U.S. National Institutes of Health.

REF 12

ClinicalTrials.gov (NCT00668070) A Proof-of-principle Study of Oral Treatment of Non-alcoholic Steatohepatitis With a Novel PDE4 Inhibitor ASP9831. U.S. National Institutes of Health.

REF 13

ClinicalTrials.gov (NCT01461941) A Phase 2 Study of E6005 in Patients With Atopic Dermatitis. U.S. National Institutes of Health.

REF 14

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 15

ClinicalTrials.gov (NCT05375955) A PHASE 2B, RANDOMIZED, DOUBLE BLIND, VEHICLE CONTROLLED, PARALLEL GROUP STUDY TO ASSESS THE EFFICACY, SAFETY, TOLERABILITY AND PHARMACOKINETICS OF MULTIPLE DOSE LEVELS OF PF-07038124 OINTMENT FOR 12 WEEKS IN PARTICIPANTS 12 YEARS AND OLDER AND WITH MILD-TO-MODERATE ATOPIC DERMATITIS OR MILD-TO-SEVERE PLAQUE PSORIASIS. U.S.National Institutes of Health.

REF 16

Emerging drugs for bacterial urinary tract infections. Expert Opin Emerg Drugs. 2005 May;10(2):275-98.

REF 17

ClinicalTrials.gov (NCT02430870) TAK-648 Multiple-Rising Dose Study in Healthy Japanese Participants and Non-Japanese Participants With Type 2 Diabetes Mellitus. U.S. National Institutes of Health.

REF 18

REF 19

Emerging drugs for asthma. Expert Opin Emerg Drugs. 2008 Dec;13(4):643-53.

REF 20

Emerging drugs for atopic dermatitis. Expert Opin Emerg Drugs. 2009 Mar;14(1):165-79.

REF 21

REF 22

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003923)

REF 23

CC-10004 . Curr Opin Investig Drugs. 2005 May;6(5):518-25.

REF 24

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

REF 25

Update on roflumilast, a phosphodiesterase 4 inhibitor for the treatment of chronic obstructive pulmonary disease.Br J Pharmacol.2011 May;163(1):53-67.

REF 26

Trial of Roflumilast Cream for Chronic Plaque Psoriasis. N Engl J Med. 2020 Jul 16;383(3):229-239.

REF 27

Clinical pipeline report, company report or official report of Arcutis Biotherapeutics.

REF 28

Lack of efficacy of an inhibitor of PDE4 in phase 1 and 2 trials of patients with nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2014 Oct;12(10):1724-30.e5.

REF 29

Antipruritic effect of the topical phosphodiesterase 4 inhibitor E6005 ameliorates skin lesions in a mouse atopic dermatitis model. J Pharmacol Exp Ther. 2013 Jul;346(1):105-12.

REF 30

Clinical pipeline report, company report or official report of Pfzer

REF 31

Ocular hypotension induced by topical dopaminergic drugs and phosphodiesterase inhibitors. Eur J Pharmacol. 1994 Jun 2;258(1-2):85-94.

REF 32

Pharmacokinetic/Pharmacodynamic Modeling of the PDE4 Inhibitor TAK-648 in Type 2 Diabetes: Early Translational Approaches for Human Dose Prediction. Clin Transl Sci. 2017 May;10(3):185-193.

REF 33

Increased interleukin-4 production by atopic mononuclear leukocytes correlates with increased cyclic adenosine monophosphate-phosphodiesterase activity and is reversible by phosphodiesterase inhibition. J Invest Dermatol. 1993 May;100(5):681-4.

REF 34

PDE4 inhibitors roflumilast and rolipram augment PGE2 inhibition of TGF-{beta}1-stimulated fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2009 Jun;296(6):L959-69.

REF 35

Phosphodiesterase 4 in osteoblastic osteosarcoma cells as a potential target for growth inhibition. Anticancer Drugs. 2003 Jun;14(5):377-81.

REF 36

The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.

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