Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTVIAT9)

• DTT Name: Phosphodiesterase 4B (PDE4B)
• Synonyms: cAMP-specific 3',5'-cyclic phosphodiesterase 4B; Type 4B cAMP phosphodiesterase; Type 4 cyclic adenosine monophosphate phosphodiesterase (type 4 PDE); PDE32; DPDE4
• Gene Name: PDE4B
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Phosphoric diester hydrolase
• UniProt ID: PDE4B_HUMAN
• TTD ID: T10265
• EC Number: EC 3.1.4.53
• Sequence:
  MKKSRSVMTVMADDNVKDYFECSLSKSYSSSSNTLGIDLWRGRRCCSGNLQLPPLSQRQS
  ERARTPEGDGISRPTTLPLTTLPSIAITTVSQECFDVENGPSPGRSPLDPQASSSAGLVL
  HATFPGHSQRRESFLYRSDSDYDLSPKAMSRNSSLPSEQHGDDLIVTPFAQVLASLRSVR
  NNFTILTNLHGTSNKRSPAASQPPVSRVNPQEESYQKLAMETLEELDWCLDQLETIQTYR
  SVSEMASNKFKRMLNRELTHLSEMSRSGNQVSEYISNTFLDKQNDVEIPSPTQKDREKKK
  KQQLMTQISGVKKLMHSSSLNNTSISRFGVNTENEDHLAKELEDLNKWGLNIFNVAGYSH
  NRPLTCIMYAIFQERDLLKTFRISSDTFITYMMTLEDHYHSDVAYHNSLHAADVAQSTHV
  LLSTPALDAVFTDLEILAAIFAAAIHDVDHPGVSNQFLINTNSELALMYNDESVLENHHL
  AVGFKLLQEEHCDIFMNLTKKQRQTLRKMVIDMVLATDMSKHMSLLADLKTMVETKKVTS
  SGVLLLDNYTDRIQVLRNMVHCADLSNPTKSLELYRQWTDRIMEEFFQQGDKERERGMEI
  SPMCDKHTASVEKSQVGFIDYIVHPLWETWADLVQPDAQDILDTLEDNRNWYQSMIPQSP
  SPPLDEQNRDCQGLMEKFQFELTLDEEDSEGPEKEGEGHSYFSSTKTLCVIDPENRDSLG
  ETDIDIATEDKSPVDT
• Function: May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents. 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

20 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BI 1015550	DM6DO2P	Idiopathic pulmonary fibrosis	CB03.4	Phase 3	[2]
DENBUFYLLINE	DM2R15Q	Cognitive impairment	6D71	Phase 3	[3]
SOTB07	DMIG4OX	Asthma	CA23	Phase 3	[1]
AN-2898	DMDK7CL	Atopic dermatitis	EA80	Phase 2	[4]
AWD-12-281	DMVADGZ	Rhinitis	FA20	Phase 2	[5]
CC-1088	DMQ874W	Crohn disease	DD70	Phase 2	[6]
GPD-1116	DMOQ7YI	Asthma	CA23	Phase 2	[7]
HT-0712	DM2WP8F	Cognitive impairment	6D71	Phase 2	[1]
LIRIMILAST	DMD4KAU	Chronic obstructive pulmonary disease	CA22	Phase 2	[8]
MK-0873	DM0568C	Psoriasis vulgaris	EA90	Phase 2	[9]
Oglemilast	DMVC90W	Asthma	CA23	Phase 2	[10]
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	[8]
AVE-8112	DMZNTHJ	Parkinson disease	8A00.0	Phase 1	[15]
GSK-356278	DMIEAMU	Huntington disease	8A01.10	Phase 1	[16]
MEM-1414	DMA1KQV	Mood disorder	6A60-6E23	Phase 1	[17]
Ronomilast	DM82KWY	Chronic obstructive pulmonary disease	CA22	Phase 1	[18]

15 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CDP840	DMUPJW4	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 2	[19]
CI-1018	DM03XVA	Asthma	CA23	Discontinued in Phase 2	[20]
Daxalipram	DMXO9BQ	Multiple sclerosis	8A40	Discontinued in Phase 2	[21]
Filaminast	DMGD5QN	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 2	[22]
KW-4490	DMSWDKX	Asthma	CA23	Discontinued in Phase 2	[23]
LAS-37779	DM9J6BX	Psoriasis vulgaris	EA90	Discontinued in Phase 2	[24]
V-11294A	DMEV1H5	Asthma	CA23	Discontinued in Phase 2	[25]
D-4418	DMUPEJK	Cutaneous T-cell lymphoma	2B01	Discontinued in Phase 1	[26]
SCH-351591	DMK40VO	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 1	[27]
YM-976	DMCDK6S	Asthma	CA23	Discontinued in Phase 1	[8]
D-22888	DM7FTCV	Allergy	4A80-4A85	Terminated	[28]
GW-3600	DMSZH0I	Asthma	CA23	Terminated	[29]
NIK-616	DM4U7XB	Chronic obstructive pulmonary disease	CA22	Terminated	[30]
TJN-598	DMKSPYI	Glomerulonephritis	5D00.Y	Terminated	[31]
Torbafylline	DMRBGI6	Peripheral vascular disease	BD4Z	Terminated	[32]

32 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(R)-Rolipram	DM95Z4Q	Discovery agent	N.A.	Investigative	[33]
(S)-Rolipram	DM1SJZ3	Discovery agent	N.A.	Investigative	[33]
3-(2-Bromophenyl)-2-thioxo-(1H )-quinazolin-4-one	DMH6I4E	Discovery agent	N.A.	Investigative	[34]
8-(3-Nitro-phenyl)-6-phenyl-[1,7]naphthyridine	DMP6Z3R	Discovery agent	N.A.	Investigative	[35]
8-Bromo-Adenosine-5'-Monophosphate	DM4CV1E	Discovery agent	N.A.	Investigative	[36]
AL-59640	DMPHTX0	Xerophthalmia	5B55.Y	Investigative	[1]
ASP-3258	DMZ9GQR	Respiratory tract inflammation	CA07	Investigative	[1]
Benzyl-(2-imidazol-1-yl-quinazolin-4-yl)-amine	DM6I5MU	Discovery agent	N.A.	Investigative	[37]
Benzyl-(2-phenyl-quinazolin-4-yl)-amine	DM3X50C	Discovery agent	N.A.	Investigative	[37]
Benzyl-(2-pyridin-3-yl-quinazolin-4-yl)-amine	DMYDGCI	Discovery agent	N.A.	Investigative	[37]
Benzyl-(2-pyridin-4-yl-quinazolin-4-yl)-amine	DMESVWC	Discovery agent	N.A.	Investigative	[37]
Benzyl-(2-thiophen-2-yl-quinazolin-4-yl)-amine	DMH318X	Discovery agent	N.A.	Investigative	[37]
CD-160130	DMT6M5E	Chronic lymphocytic leukaemia	2A82.0	Investigative	[1]
CH-3697	DM0RFTJ	Asthma	CA23	Investigative	[1]
CHF-5480	DM5T64L	Chronic obstructive pulmonary disease	CA22	Investigative	[1]
CI-1044	DMG5D6B	Discovery agent	N.A.	Investigative	[38]
isobutylmethylxanthine	DM46F5X	Discovery agent	N.A.	Investigative	[39]
KF-66490	DMOUW0A	Atopic dermatitis	EA80	Investigative	[40]
KURAIDIN	DMLDUJ1	Discovery agent	N.A.	Investigative	[41]
KURARINOL	DMRV5YE	Discovery agent	N.A.	Investigative	[41]
L-454560	DM0P4V6	Discovery agent	N.A.	Investigative	[42]
L-869298	DMKEDU6	Discovery agent	N.A.	Investigative	[43]
NITRAQUAZONE	DMVDM0Q	Discovery agent	N.A.	Investigative	[44]
OCID-2987	DM69O3S	Inflammation	1A00-CA43.1	Investigative	[1]
ROLIPRAM	DMJ03UM	Discovery agent	N.A.	Investigative	[45]
RS-14491	DMRW57G	Discovery agent	N.A.	Investigative	[45]
RS-25344	DM0W2IS	Discovery agent	N.A.	Investigative	[46]
S,S-(2-Hydroxyethyl)Thiocysteine	DMLPAD8	Discovery agent	N.A.	Investigative	[22]
SOPHOFLAVESCENOL	DM8Y1S7	Discovery agent	N.A.	Investigative	[41]
TAS-203	DM07FBL	Respiratory tract inflammation	CA07	Investigative	[1]
UCB-101333-3	DMHYORU	Discovery agent	N.A.	Investigative	[47]
ZL-N-91	DM1H865	Lung inflammation	CA40.Z	Investigative	[1]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Psoriasis	EA90	Skin	4.33E-11	-0.48	-0.51
Parkinson's disease	8A00.0	Substantia nigra tissue	2.75E-01	-0.13	-0.3
Asthma	CA23	Nasal and bronchial airway	2.60E-01	0.06	0.11
Atopic dermatitis	EA90	Skin	4.84E-01	-1.75E-03	-2.79E-03
Chronic obstructive pulmonary disease	CA23	Lung tissue	1.56E-01	0.17	0.21
Chronic obstructive pulmonary disease	CA23	Small airway epithelium	2.90E-01	0.02	0.03
Rheumatoid arthritis	FA20	Synovial tissue	1.97E-08	1.93	5.67
Sepsis with septic shock	1G41	Whole blood	2.94E-27	-1	-1.22

References

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