Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Phosphodiesterase 9 (PDE9)
• Synonyms: High affinity cGMPspecific 3',5'cyclic phosphodiesterase 9A; High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A
• Gene Name: PDE9A
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Phosphoric diester hydrolase
• UniProt ID: PDE9A_HUMAN
• TTD ID: T17852
• EC Number: EC 3.1.4.35
• Sequence:
  MGSGSSSYRPKAIYLDIDGRIQKVIFSKYCNSSDIMDLFCIATGLPRNTTISLLTTDDAM
  VSIDPTMPANSERTPYKVRPVAIKQLSAGVEDKRTTSRGQSAERPLRDRRVVGLEQPRRE
  GAFESGQVEPRPREPQGCYQEGQRIPPEREELIQSVLAQVAEQFSRAFKINELKAEVANH
  LAVLEKRVELEGLKVVEIEKCKSDIKKMREELAARSSRTNCPCKYSFLDNHKKLTPRRDV
  PTYPKYLLSPETIEALRKPTFDVWLWEPNEMLSCLEHMYHDLGLVRDFSINPVTLRRWLF
  CVHDNYRNNPFHNFRHCFCVAQMMYSMVWLCSLQEKFSQTDILILMTAAICHDLDHPGYN
  NTYQINARTELAVRYNDISPLENHHCAVAFQILAEPECNIFSNIPPDGFKQIRQGMITLI
  LATDMARHAEIMDSFKEKMENFDYSNEEHMTLLKMILIKCCDISNEVRPMEVAEPWVDCL
  LEEYFMQSDREKSEGLPVAPFMDRDKVTKATAQIGFIKFVLIPMFETVTKLFPMVEEIML
  QPLWESRDRYEELKRIDDAMKELQKKTDSLTSGATEKSRERSRDVKNSEGDCA
• Function: Highly specific: compared to other members of the cyclic nucleotide phosphodiesterase family, has the highest affinity and selectivity for cGMP. Specifically regulates natriuretic-peptide-dependent cGMP signaling in heart, acting as a regulator of cardiac hypertrophy in myocytes and muscle. Does not regulate nitric oxide-dependent cGMP in heart. Additional experiments are required to confirm whether its ability to hydrolyze natriuretic-peptide-dependent cGMP is specific to heart or is a general feature of the protein. In brain, involved in cognitive function, such as learning and long-term memory. Specifically hydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes.
• KEGG Pathway: Purine metabolism (hsa00230)
• Reactome Pathway: cGMP effects (R-HSA-418457)

Molecular Interaction Atlas (MIA) of This DTT

7 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ASP-4901	DMZUAH2	Genitourinary disease	GA0Z-GC8Z	Phase 2	[2]
BI-409306	DMJFDS0	Alzheimer disease	8A20	Phase 2	[3]
CRD-740	DMRTX0K	Heart failure	BD10-BD13	Phase 2	[4]
E2027	DMK8SY6	Lewy body dementia	6D82	Phase 2	[5]
IMR-687	DM15MRZ	Sickle-cell disorder	3A51	Phase 2	[6]
PF-4447943	DM81D4I	Alzheimer disease	8A20	Phase 2	[1]
TT-00920	DMP6G0P	Heart failure	BD10-BD13	Phase 1	[7]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PF-4181366	DMC8G4S	Cognitive impairment	6D71	Investigative	[8]
SCH51866	DMCWSJP	Discovery agent	N.A.	Investigative	[9]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Alzheimer's disease	8A00.0	Entorhinal cortex	8.73E-03	0.07	0.36

References

• [1] A multicenter, double-blind, placebo-controlled trial of the PDE9A inhibitor, PF-04447943, in Alzheimer's disease. Curr Alzheimer Res. 2014;11(5):413-21.
• [2] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033070)
• [3] Clinical pipeline report, company report or official report of Boehringer Ingelheim pipeline.
• [4] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2023. Adis Insight
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Clinical pipeline report, company report or official report of Imara.
• [7] Clinical pipeline report, company report or official report of TransThera Biosciences
• [8] 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. (Target id: 1309).
• [9] Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase. J Biol Chem. 1998 Jun 19;273(25):15559-64.