Target Information
Target General Information | Top | |||||
---|---|---|---|---|---|---|
Target ID |
T47941
(Former ID: TTDC00170)
|
|||||
Target Name |
Phosphodiesterase 4 (PDE4)
|
|||||
Synonyms |
PDE-4
Click to Show/Hide
|
|||||
Gene Name |
NO-GeName
|
|||||
Target Type |
Successful target
|
[1] | ||||
Disease | [+] 5 Target-related Diseases | + | ||||
1 | Asthma [ICD-11: CA23] | |||||
2 | Atopic eczema [ICD-11: EA80] | |||||
3 | Castlemans disease [ICD-11: 4B2Y] | |||||
4 | Cough [ICD-11: MD12] | |||||
5 | 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
Click to Show/Hide
|
|||||
BioChemical Class |
Phosphoric diester hydrolase
|
|||||
UniProt ID |
Drugs and Modes of Action | Top | |||||
---|---|---|---|---|---|---|
Approved Drug(s) | [+] 5 Approved Drugs | + | ||||
1 | Apremilast | Drug Info | Approved | Psoriasis vulgaris | [2], [3] | |
2 | crisaborole | Drug Info | Approved | Atopic dermatitis | [4] | |
3 | Ibudilast | Drug Info | Approved | Castleman's disease | [5] | |
4 | Oxtriphylline | Drug Info | Approved | Cough | [6] | |
5 | Roflumilast | Drug Info | Approved | Asthma | [7], [8] | |
Clinical Trial Drug(s) | [+] 5 Clinical Trial Drugs | + | ||||
1 | Arofylline | Drug Info | Phase 3 | Chronic obstructive pulmonary disease | [10] | |
2 | E6005 | Drug Info | Phase 2 | Atopic dermatitis | [15] | |
3 | IC-485 | Drug Info | Phase 2 | Chronic obstructive pulmonary disease | [10] | |
4 | ONO-6126 | Drug Info | Phase 2 | Chronic obstructive pulmonary disease | [10] | |
5 | SUN13834 | Drug Info | Phase 2 | Gram-positive bacterial infection | [16] | |
Discontinued Drug(s) | [+] 3 Discontinued Drugs | + | ||||
1 | Cilomilast | Drug Info | Discontinued in Phase 3 | Chronic obstructive pulmonary disease | [18], [19] | |
2 | GW842470X | Drug Info | Discontinued in Phase 2 | Atopic dermatitis | [20] | |
3 | Ro 20-1724 | Drug Info | Terminated | Asthma | [21], [22] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Inhibitor | [+] 14 Inhibitor drugs | + | ||||
1 | Apremilast | Drug Info | [1], [3], [23] | |||
2 | Ibudilast | Drug Info | [5] | |||
3 | Arofylline | Drug Info | [10] | |||
4 | E6005 | Drug Info | [26] | |||
5 | IC-485 | Drug Info | [10] | |||
6 | ONO-6126 | Drug Info | [10] | |||
7 | SUN13834 | Drug Info | [27] | |||
8 | Cilomilast | Drug Info | [10] | |||
9 | GW842470X | Drug Info | [20] | |||
10 | Ro 20-1724 | Drug Info | [28] | |||
11 | (R)-Rolipram | Drug Info | [29], [30] | |||
12 | (S)-Rolipram | Drug Info | [29], [30] | |||
13 | Iso-caffeine | Drug Info | [27] | |||
14 | S-(-)-enantiomer of 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP) | Drug Info | [27] | |||
Modulator | [+] 5 Modulator drugs | + | ||||
1 | crisaborole | Drug Info | [4] | |||
2 | Oxtriphylline | Drug Info | [24] | |||
3 | Roflumilast | Drug Info | [8], [25] | |||
4 | CT-5357 | Drug Info | [31] | |||
5 | SDZ-PDI-747 | Drug Info | [31] |
Chemical Structure based Activity Landscape of Target | Top |
---|---|
Drug Property Profile of Target | Top | |
---|---|---|
(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 | Top | |||||
---|---|---|---|---|---|---|
Co-Targets |
Target Poor or Non Binders | Top | |||||
---|---|---|---|---|---|---|
Target Poor or Non Binders |
Target-Related Models and Studies | Top | |||||
---|---|---|---|---|---|---|
Target Validation |
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 | 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: 6962). | |||||
REF 8 | 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4. | |||||
REF 9 | 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 10 | Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91. | |||||
REF 11 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
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 (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 14 | 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 15 | ClinicalTrials.gov (NCT01461941) A Phase 2 Study of E6005 in Patients With Atopic Dermatitis. 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 | 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: 7407). | |||||
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 | 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: 5258). | |||||
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 | 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 27 | Ocular hypotension induced by topical dopaminergic drugs and phosphodiesterase inhibitors. Eur J Pharmacol. 1994 Jun 2;258(1-2):85-94. | |||||
REF 28 | 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 29 | 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 30 | Phosphodiesterase 4 in osteoblastic osteosarcoma cells as a potential target for growth inhibition. Anticancer Drugs. 2003 Jun;14(5):377-81. | |||||
REF 31 | The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954. |
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.