Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T17852
(Former ID: TTDI02148)
|
|||||
| Target 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
|
|||||
| Target Type |
Clinical trial target
|
[1] | ||||
| Disease | [+] 7 Target-related Diseases | + | ||||
| 1 | Dementia [ICD-11: 6D80-6D8Z] | |||||
| 2 | Genitourinary disease [ICD-11: GA0Z-GC8Z] | |||||
| 3 | Mental/behavioural/neurodevelopmental disorder [ICD-11: 6E20-6E8Z] | |||||
| 4 | Parkinsonism [ICD-11: 8A00] | |||||
| 5 | Schizophrenia [ICD-11: 6A20] | |||||
| 6 | Sickle-cell disorder [ICD-11: 3A51] | |||||
| 7 | Alzheimer disease [ICD-11: 8A20] | |||||
| 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.
Click to Show/Hide
|
|||||
| BioChemical Class |
Phosphoric diester hydrolase
|
|||||
| UniProt ID | ||||||
| EC Number |
EC 3.1.4.35
|
|||||
| Sequence |
MGSGSSSYRPKAIYLDIDGRIQKVIFSKYCNSSDIMDLFCIATGLPRNTTISLLTTDDAM
VSIDPTMPANSERTPYKVRPVAIKQLSAGVEDKRTTSRGQSAERPLRDRRVVGLEQPRRE GAFESGQVEPRPREPQGCYQEGQRIPPEREELIQSVLAQVAEQFSRAFKINELKAEVANH LAVLEKRVELEGLKVVEIEKCKSDIKKMREELAARSSRTNCPCKYSFLDNHKKLTPRRDV PTYPKYLLSPETIEALRKPTFDVWLWEPNEMLSCLEHMYHDLGLVRDFSINPVTLRRWLF CVHDNYRNNPFHNFRHCFCVAQMMYSMVWLCSLQEKFSQTDILILMTAAICHDLDHPGYN NTYQINARTELAVRYNDISPLENHHCAVAFQILAEPECNIFSNIPPDGFKQIRQGMITLI LATDMARHAEIMDSFKEKMENFDYSNEEHMTLLKMILIKCCDISNEVRPMEVAEPWVDCL LEEYFMQSDREKSEGLPVAPFMDRDKVTKATAQIGFIKFVLIPMFETVTKLFPMVEEIML QPLWESRDRYEELKRIDDAMKELQKKTDSLTSGATEKSRERSRDVKNSEGDCA Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Clinical Trial Drug(s) | [+] 5 Clinical Trial Drugs | + | ||||
| 1 | ASP-4901 | Drug Info | Phase 2 | Genitourinary disease | [2] | |
| 2 | BI-409306 | Drug Info | Phase 2 | Psychiatric disorder | [3] | |
| 3 | E2027 | Drug Info | Phase 2 | Parkinson disease | [4] | |
| 4 | IMR-687 | Drug Info | Phase 2 | Sickle-cell disorder | [5] | |
| 5 | PF-4447943 | Drug Info | Phase 2 | Alzheimer disease | [6] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 6 Inhibitor drugs | + | ||||
| 1 | ASP-4901 | Drug Info | [7] | |||
| 2 | BI-409306 | Drug Info | [8] | |||
| 3 | IMR-687 | Drug Info | [11] | |||
| 4 | PF-4447943 | Drug Info | [1] | |||
| 5 | PF-4181366 | Drug Info | [12] | |||
| 6 | SCH51866 | Drug Info | [13] | |||
| Antagonist | [+] 1 Antagonist drugs | + | ||||
| 1 | E2027 | Drug Info | [9], [10] | |||
| 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 | ||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Purine metabolism | |||||
| PID Pathway | [+] 1 PID Pathways | + | ||||
| 1 | Regulation of Androgen receptor activity | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | cGMP effects | |||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 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. | |||||
| REF 2 | ClinicalTrials.gov (NCT02038868) A Study to Evaluate the Efficacy and Safety of ASP4901 in Patients With Benign Prostate Hyperplasia. U.S. National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT02240693) Alzheimer Disease Proof of Concept Study With BI 409306 Versus Placebo. U.S. National Institutes of Health. | |||||
| REF 4 | ClinicalTrials.gov (NCT04764669) A Study of E2027 in Participants With Dementia With Lewy Bodies (DLB) or Parkinson's Disease Dementia (PDD) With or Without Amyloid Copathology. U.S. National Institutes of Health. | |||||
| REF 5 | ClinicalTrials.gov (NCT03401112) A Study of IMR-687 in Adult Patients With Sickle Cell Anaemia (Homozygous HbSS or Sickle-beta0 Thalassemia). U.S. National Institutes of Health. | |||||
| REF 6 | ClinicalTrials.gov (NCT00930059) A Study Of PF-04447943 Compared To Placebo In Subjects With Mild To Moderate Alzheimer's Disease. U.S. National Institutes of Health. | |||||
| REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033070) | |||||
| REF 8 | Clinical pipeline report, company report or official report of Boehringer Ingelheim pipeline. | |||||
| REF 9 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 10 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 11 | Clinical pipeline report, company report or official report of Imara. | |||||
| REF 12 | 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). | |||||
| REF 13 | Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase. J Biol Chem. 1998 Jun 19;273(25):15559-64. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.