Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTV5CGO)

• DTT Name: Phosphodiesterase 4 (PDE4)
• Synonyms: PDE-4
• Gene Name: PDE4
• DTT Type: Successful target; [1]
• BioChemical Class: Phosphoric diester hydrolase
• UniProt ID: NOUNIPROTAC
• TTD ID: T47941
• 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

Molecular Interaction Atlas (MIA) of This DTT

5 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Apremilast	DMTWS9E	Psoriasis vulgaris	EA90	Approved	[1]
crisaborole	DMNVKU6	Atopic dermatitis	EA80	Approved	[2]
Ibudilast	DM4LSPN	Castleman's disease	4B2Y	Approved	[3]
Oxtriphylline	DMLHSE3	Cough	MD12	Approved	[4]
Roflumilast	DMPGHY8	Asthma	CA23	Approved	[5]

11 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Arofylline	DM84AD1	Chronic obstructive pulmonary disease	CA22	Phase 3	[6]
ARQ-151	DML61S4	Atopic dermatitis	EA80	Phase 3	[7]
ARQ-154	DMYEIOH	Plaque psoriasis	EA90.0	Phase 2	[8]
ASP9831	DM2MSGF	Non-alcoholic steatohepatitis	DB92.1	Phase 2	[9]
E6005	DM1S489	Atopic dermatitis	EA80	Phase 2	[10]
IC-485	DMB1UYV	Chronic obstructive pulmonary disease	CA22	Phase 2	[6]
LEO-32731	DMZ6Y0T	Plaque psoriasis	EA90.0	Phase 2	[11]
ONO-6126	DMRT28X	Chronic obstructive pulmonary disease	CA22	Phase 2	[6]
PF-07038124	DMI4RUI	Atopic dermatitis	EA80	Phase 2	[12]
SUN13834	DMPK34E	Gram-positive bacterial infection	1B74-1G40	Phase 2	[13]
TAK-648	DMQ8YKR	Type 2 diabetes	5A11	Phase 1	[14]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cilomilast	DMHSM7I	Bronchitis	CA20	Discontinued in Phase 3	[6]
GW842470X	DMLC154	Atopic dermatitis	EA80	Discontinued in Phase 2	[15]
Ro 20-1724	DM0PSCF	Asthma	CA23	Terminated	[16]

6 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(R)-Rolipram	DM95Z4Q	Discovery agent	N.A.	Investigative	[17]
(S)-Rolipram	DM1SJZ3	Discovery agent	N.A.	Investigative	[17]
CT-5357	DM6W9LA	Discovery agent	N.A.	Investigative	[18]
Iso-caffeine	DM861DU	Discovery agent	N.A.	Investigative	[13]
S-(-)-enantiomer of 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP)	DMQG4L2	Discovery agent	N.A.	Investigative	[13]
SDZ-PDI-747	DM3GJ07	Discovery agent	N.A.	Investigative	[18]

References

• [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.
• [2] 2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76.
• [3] Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond. Nat Rev Drug Discov. 2019 Oct;18(10):770-796.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [6] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
• [7] Trial of Roflumilast Cream for Chronic Plaque Psoriasis. N Engl J Med. 2020 Jul 16;383(3):229-239.
• [8] Clinical pipeline report, company report or official report of Arcutis Biotherapeutics.
• [9] 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.
• [10] 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.
• [11] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [12] Clinical pipeline report, company report or official report of Pfzer
• [13] Ocular hypotension induced by topical dopaminergic drugs and phosphodiesterase inhibitors. Eur J Pharmacol. 1994 Jun 2;258(1-2):85-94.
• [14] 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.
• [15] Emerging drugs for atopic dermatitis. Expert Opin Emerg Drugs. 2009 Mar;14(1):165-79.
• [16] 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.
• [17] 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.
• [18] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.