Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTZ97H5)

• DTT Name: Phosphodiesterase 4A (PDE4A)
• Synonyms: cAMP-specific 3',5'-cyclic phosphodiesterase 4A; Type 4A cAMP phosphodiesterase; PDE46; DPDE2
• Gene Name: PDE4A
• DTT Type: Successful target; [1]
• BioChemical Class: Phosphoric diester hydrolase
• UniProt ID: PDE4A_HUMAN
• TTD ID: T61744
• EC Number: EC 3.1.4.53
• Sequence:
  MEPPTVPSERSLSLSLPGPREGQATLKPPPQHLWRQPRTPIRIQQRGYSDSAERAERERQ
  PHRPIERADAMDTSDRPGLRTTRMSWPSSFHGTGTGSGGAGGGSSRRFEAENGPTPSPGR
  SPLDSQASPGLVLHAGAATSQRRESFLYRSDSDYDMSPKTMSRNSSVTSEAHAEDLIVTP
  FAQVLASLRSVRSNFSLLTNVPVPSNKRSPLGGPTPVCKATLSEETCQQLARETLEELDW
  CLEQLETMQTYRSVSEMASHKFKRMLNRELTHLSEMSRSGNQVSEYISTTFLDKQNEVEI
  PSPTMKEREKQQAPRPRPSQPPPPPVPHLQPMSQITGLKKLMHSNSLNNSNIPRFGVKTD
  QEELLAQELENLNKWGLNIFCVSDYAGGRSLTCIMYMIFQERDLLKKFRIPVDTMVTYML
  TLEDHYHADVAYHNSLHAADVLQSTHVLLATPALDAVFTDLEILAALFAAAIHDVDHPGV
  SNQFLINTNSELALMYNDESVLENHHLAVGFKLLQEDNCDIFQNLSKRQRQSLRKMVIDM
  VLATDMSKHMTLLADLKTMVETKKVTSSGVLLLDNYSDRIQVLRNMVHCADLSNPTKPLE
  LYRQWTDRIMAEFFQQGDRERERGMEISPMCDKHTASVEKSQVGFIDYIVHPLWETWADL
  VHPDAQEILDTLEDNRDWYYSAIRQSPSPPPEEESRGPGHPPLPDKFQFELTLEEEEEEE
  ISMAQIPCTAQEALTAQGLSGVEEALDATIAWEASPAQESLEVMAQEASLEAELEAVYLT
  QQAQSTGSAPVAPDEFSSREEFVVAVSHSSPSALALQSPLLPAWRTLSVSEHAPGLPGLP
  STAAEVEAQREHQAAKRACSACAGTFGEDTSALPAPGGGGSGGDPT
• Function: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  cAMP signaling pathway (hsa04024)
  Morphine addiction (hsa05032)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  DARPP-32 events (R-HSA-180024)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dyphylline	DM8DZC1	Acute bronchial asthma	CA23	Approved	[1]
Enprofylline	DMFYZKN	Asthma	CA23	Approved	[2]

20 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DENBUFYLLINE	DM2R15Q	Cognitive impairment	6D71	Phase 3	[3]
SOTB07	DMIG4OX	Asthma	CA23	Phase 3	[4]
AN-2898	DMDK7CL	Atopic dermatitis	EA80	Phase 2	[5]
AWD-12-281	DMVADGZ	Rhinitis	FA20	Phase 2	[6]
CC-1088	DMQ874W	Crohn disease	DD70	Phase 2	[7]
GPD-1116	DMOQ7YI	Asthma	CA23	Phase 2	[8]
HT-0712	DM2WP8F	Cognitive impairment	6D71	Phase 2	[4]
LIRIMILAST	DMD4KAU	Chronic obstructive pulmonary disease	CA22	Phase 2	[9]
MK-0873	DM0568C	Psoriasis vulgaris	EA90	Phase 2	[10]
Oglemilast	DMVC90W	Asthma	CA23	Phase 2	[9]
OX-914	DM5Q9RY	Asthma	CA23	Phase 2	[11]
Piclamilast	DMYL7VR	Rheumatoid arthritis	FA20	Phase 2	[12]
Revamilast	DM1FS2W	Asthma	CA23	Phase 2	[13]
TA-7906	DMZTAJL	Atopic dermatitis	EA80	Phase 2	[14]
TOFIMILAST	DMLCUAS	Chronic obstructive pulmonary disease	CA22	Phase 2	[15]
Tofisopam	DMTGNWU	Hyperuricaemia	5C55.Y	Phase 2	[16]
AVE-8112	DMZNTHJ	Parkinson disease	8A00.0	Phase 1	[17]
GSK-356278	DMIEAMU	Huntington disease	8A01.10	Phase 1	[18]
MEM-1414	DMA1KQV	Mood disorder	6A60-6E23	Phase 1	[19]
Ronomilast	DM82KWY	Chronic obstructive pulmonary disease	CA22	Phase 1	[20]

16 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cilomilast	DMHSM7I	Bronchitis	CA20	Discontinued in Phase 3	[21]
CDP840	DMUPJW4	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 2	[22]
CI-1018	DM03XVA	Asthma	CA23	Discontinued in Phase 2	[23]
Daxalipram	DMXO9BQ	Multiple sclerosis	8A40	Discontinued in Phase 2	[24]
GSK256066	DMBYQJH	Asthma	CA23	Discontinued in Phase 2	[25]
KW-4490	DMSWDKX	Asthma	CA23	Discontinued in Phase 2	[26]
LAS-37779	DM9J6BX	Psoriasis vulgaris	EA90	Discontinued in Phase 2	[27]
V-11294A	DMEV1H5	Asthma	CA23	Discontinued in Phase 2	[28]
D-4418	DMUPEJK	Cutaneous T-cell lymphoma	2B01	Discontinued in Phase 1	[29]
SCH-351591	DMK40VO	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 1	[30]
YM-976	DMCDK6S	Asthma	CA23	Discontinued in Phase 1	[31]
D-22888	DM7FTCV	Allergy	4A80-4A85	Terminated	[32]
GW-3600	DMSZH0I	Asthma	CA23	Terminated	[33]
NIK-616	DM4U7XB	Chronic obstructive pulmonary disease	CA22	Terminated	[34]
TJN-598	DMKSPYI	Glomerulonephritis	5D00.Y	Terminated	[35]
Torbafylline	DMRBGI6	Peripheral vascular disease	BD4Z	Terminated	[36]

42 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(2,5-Diphenyl-furan-3-yl)-phenyl-methanone	DM97GFB	Discovery agent	N.A.	Investigative	[37]
(R)-Rolipram	DM95Z4Q	Discovery agent	N.A.	Investigative	[38]
(S)-Rolipram	DM1SJZ3	Discovery agent	N.A.	Investigative	[38]
1-Butyl-3-methyl-3,7-dihydro-purine-2,6-dione	DM9GRN8	Discovery agent	N.A.	Investigative	[39]
1-Methyl-3-propyl-3,7-dihydro-purine-2,6-dione	DM90LWT	Discovery agent	N.A.	Investigative	[39]
2,5-Bis-(3,4-dimethoxy-phenyl)-furan	DMH6RDL	Discovery agent	N.A.	Investigative	[37]
2,5-Bis-(3-cyclopentyloxy-4-methoxy-phenyl)-furan	DM28GQS	Discovery agent	N.A.	Investigative	[37]
4-(2,5-Diphenyl-furan-3-yl)-morpholine	DMVYALJ	Discovery agent	N.A.	Investigative	[37]
6-Azido-8-(3-iodo-phenyl)-quinoline	DM8BNWH	Discovery agent	N.A.	Investigative	[40]
6-Imidazol-1-ylmethyl-8-phenyl-quinoline	DMBQ3HV	Discovery agent	N.A.	Investigative	[40]
8-(3-Azido-phenyl)-6-iodo-quinoline	DM9J2LT	Discovery agent	N.A.	Investigative	[40]
8-(3-Azido-phenyl)-6-pyridin-4-ylmethyl-quinoline	DMON7RZ	Discovery agent	N.A.	Investigative	[40]
8-(3-Nitro-phenyl)-6-phenyl-[1,7]naphthyridine	DMP6Z3R	Discovery agent	N.A.	Investigative	[41]
8-(3-Nitro-phenyl)-6-pyridin-4-ylmethyl-quinoline	DM0N68L	Discovery agent	N.A.	Investigative	[40]
AL-59640	DMPHTX0	Xerophthalmia	5B55.Y	Investigative	[4]
ASP-3258	DMZ9GQR	Respiratory tract inflammation	CA07	Investigative	[4]
Benzyl-(2-imidazol-1-yl-quinazolin-4-yl)-amine	DM6I5MU	Discovery agent	N.A.	Investigative	[42]
Benzyl-(2-phenyl-quinazolin-4-yl)-amine	DM3X50C	Discovery agent	N.A.	Investigative	[42]
Benzyl-(2-pyridin-3-yl-quinazolin-4-yl)-amine	DMYDGCI	Discovery agent	N.A.	Investigative	[42]
Benzyl-(2-pyridin-4-yl-quinazolin-4-yl)-amine	DMESVWC	Discovery agent	N.A.	Investigative	[42]
Benzyl-(2-thiophen-2-yl-quinazolin-4-yl)-amine	DMH318X	Discovery agent	N.A.	Investigative	[42]
CD-160130	DMT6M5E	Chronic lymphocytic leukaemia	2A82.0	Investigative	[4]
CH-3697	DM0RFTJ	Asthma	CA23	Investigative	[4]
CHF-5480	DM5T64L	Chronic obstructive pulmonary disease	CA22	Investigative	[4]
CI-1044	DMG5D6B	Discovery agent	N.A.	Investigative	[43]
isobutylmethylxanthine	DM46F5X	Discovery agent	N.A.	Investigative	[44]
KF-66490	DMOUW0A	Atopic dermatitis	EA80	Investigative	[45]
KURAIDIN	DMLDUJ1	Discovery agent	N.A.	Investigative	[46]
KURARINOL	DMRV5YE	Discovery agent	N.A.	Investigative	[46]
L-454560	DM0P4V6	Discovery agent	N.A.	Investigative	[47]
L-791943	DM5D892	Discovery agent	N.A.	Investigative	[48]
L-869298	DMKEDU6	Discovery agent	N.A.	Investigative	[49]
NIS-62949	DM1R0WC	Discovery agent	N.A.	Investigative	[50]
NITRAQUAZONE	DMVDM0Q	Discovery agent	N.A.	Investigative	[51]
OCID-2987	DM69O3S	Inflammation	1A00-CA43.1	Investigative	[4]
ROLIPRAM	DMJ03UM	Discovery agent	N.A.	Investigative	[52]
RS-14491	DMRW57G	Discovery agent	N.A.	Investigative	[53]
RS-25344	DM0W2IS	Discovery agent	N.A.	Investigative	[54]
SOPHOFLAVESCENOL	DM8Y1S7	Discovery agent	N.A.	Investigative	[46]
TAS-203	DM07FBL	Respiratory tract inflammation	CA07	Investigative	[4]
UCB-101333-3	DMHYORU	Discovery agent	N.A.	Investigative	[55]
ZL-N-91	DM1H865	Lung inflammation	CA40.Z	Investigative	[4]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Psoriasis	EA90	Skin	3.88E-01	4.09E-03	1.09E-02
Parkinson's disease	8A00.0	Substantia nigra tissue	9.26E-01	-3.01E-03	-0.01
Rheumatoid arthritis	FA20	Synovial tissue	6.55E-01	1.40E-02	0.04
Asthma	CA23	Nasal and bronchial airway	3.49E-01	0.02	0.04
Atopic dermatitis	EA90	Skin	4.11E-02	-0.19	-0.77
Chronic obstructive pulmonary disease	CA23	Lung tissue	3.80E-01	-0.13	-0.29
Chronic obstructive pulmonary disease	CA23	Small airway epithelium	4.41E-03	0.12	0.44
Sepsis with septic shock	1G41	Whole blood	6.13E-01	-0.06	-0.19

References

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