Target Information
| Target General Information | Top | |||||
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| Target ID |
T77400
(Former ID: TTDR00256)
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| Target Name |
Phosphodiesterase 2A (PDE2A)
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| Synonyms |
cGMP-dependent 3',5'-cyclic phosphodiesterase; PDE-II; Cyclic-GMP phosphodiesterase; Cyclic GMP-stimulated phosphodiesterase; Cyclic GMP stimulated phosphodiesterase; CGSPDE; CGS-PDE
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| Gene Name |
PDE2A
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 4 Target-related Diseases | + | ||||
| 1 | Inborn purine/pyrimidine/nucleotide metabolism error [ICD-11: 5C55] | |||||
| 2 | Indeterminate colitis [ICD-11: DD72] | |||||
| 3 | Irritable bowel syndrome [ICD-11: DD91] | |||||
| 4 | Mood disorder [ICD-11: 6A60-6E23] | |||||
| Function |
Plays an important role in growth and invasion of malignant melanoma cells (e. g. pseudomyxoma peritonei (PMP) cell line). Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.
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| BioChemical Class |
Phosphoric diester hydrolase
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| UniProt ID | ||||||
| EC Number |
EC 3.1.4.17
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| Sequence |
MGQACGHSILCRSQQYPAARPAEPRGQQVFLKPDEPPPPPQPCADSLQDALLSLGSVIDI
SGLQRAVKEALSAVLPRVETVYTYLLDGESQLVCEDPPHELPQEGKVREAIISQKRLGCN GLGFSDLPGKPLARLVAPLAPDTQVLVMPLADKEAGAVAAVILVHCGQLSDNEEWSLQAV EKHTLVALRRVQVLQQRGPREAPRAVQNPPEGTAEDQKGGAAYTDRDRKILQLCGELYDL DASSLQLKVLQYLQQETRASRCCLLLVSEDNLQLSCKVIGDKVLGEEVSFPLTGCLGQVV EDKKSIQLKDLTSEDVQQLQSMLGCELQAMLCVPVISRATDQVVALACAFNKLEGDLFTD EDEHVIQHCFHYTSTVLTSTLAFQKEQKLKCECQALLQVAKNLFTHLDDVSVLLQEIITE ARNLSNAEICSVFLLDQNELVAKVFDGGVVDDESYEIRIPADQGIAGHVATTGQILNIPD AYAHPLFYRGVDDSTGFRTRNILCFPIKNENQEVIGVAELVNKINGPWFSKFDEDLATAF SIYCGISIAHSLLYKKVNEAQYRSHLANEMMMYHMKVSDDEYTKLLHDGIQPVAAIDSNF ASFTYTPRSLPEDDTSMAILSMLQDMNFINNYKIDCPTLARFCLMVKKGYRDPPYHNWMH AFSVSHFCYLLYKNLELTNYLEDIEIFALFISCMCHDLDHRGTNNSFQVASKSVLAALYS SEGSVMERHHFAQAIAILNTHGCNIFDHFSRKDYQRMLDLMRDIILATDLAHHLRIFKDL QKMAEVGYDRNNKQHHRLLLCLLMTSCDLSDQTKGWKTTRKIAELIYKEFFSQGDLEKAM GNRPMEMMDREKAYIPELQISFMEHIAMPIYKLLQDLFPKAAELYERVASNREHWTKVSH KFTIRGLPSNNSLDFLDEEYEVPDLDGTRAPINGCCSLDAE Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T99TRQ | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | CP-461 | Drug Info | Phase 2 | Inflammatory bowel disease | [2] | |
| 2 | Tofisopam | Drug Info | Phase 2 | Irritable bowel syndrome | [3] | |
| 3 | ND7001 | Drug Info | Phase 1 | Mood disorder | [4] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 65 Inhibitor drugs | + | ||||
| 1 | CP-461 | Drug Info | [1] | |||
| 2 | Tofisopam | Drug Info | [5] | |||
| 3 | 1,2,4-triazole [1,5-a]pyrimidin-7-yl derivative 1 | Drug Info | [6] | |||
| 4 | 1,2,4-triazole [1,5-a]pyrimidin-7-yl derivative 2 | Drug Info | [6] | |||
| 5 | 1,2,4-triazole [1,5-a]pyrimidin-7-yl derivative 3 | Drug Info | [6] | |||
| 6 | 1,2,4-triazole [4,3-a]quinoxaline derivative 1 | Drug Info | [6] | |||
| 7 | 1,2,4-triazole [4,3-a]quinoxaline derivative 2 | Drug Info | [6] | |||
| 8 | 1,2,4-triazole [4,3-a]quinoxaline derivative 3 | Drug Info | [6] | |||
| 9 | 1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]quinoxaline derivative 1 | Drug Info | [6] | |||
| 10 | 1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]quinoxaline derivative 2 | Drug Info | [6] | |||
| 11 | 1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]quinoxaline derivative 3 | Drug Info | [6] | |||
| 12 | 1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]quinoxaline derivative 4 | Drug Info | [6] | |||
| 13 | 1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]quinoxaline derivative 5 | Drug Info | [6] | |||
| 14 | 1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]quinoxaline derivative 6 | Drug Info | [6] | |||
| 15 | Benzodiazepine derivative 2 | Drug Info | [6] | |||
| 16 | Imidazo triazine derivative 1 | Drug Info | [6] | |||
| 17 | Imidazo triazine derivative 2 | Drug Info | [6] | |||
| 18 | Imidazo triazine derivative 3 | Drug Info | [6] | |||
| 19 | Imidazo triazine derivative 4 | Drug Info | [6] | |||
| 20 | Imidazo triazine derivative 5 | Drug Info | [6] | |||
| 21 | Imidazotriazinone derivative 1 | Drug Info | [6] | |||
| 22 | Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 1 | Drug Info | [6] | |||
| 23 | Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 2 | Drug Info | [6] | |||
| 24 | Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 3 | Drug Info | [6] | |||
| 25 | Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 4 | Drug Info | [6] | |||
| 26 | Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 5 | Drug Info | [6] | |||
| 27 | Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 6 | Drug Info | [6] | |||
| 28 | Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 7 | Drug Info | [6] | |||
| 29 | Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 8 | Drug Info | [6] | |||
| 30 | Imidazo[5,1-c][1,2,4]benzotriazine derivative 1 | Drug Info | [6] | |||
| 31 | Imidazo[5,1-c][1,2,4]benzotriazine derivative 2 | Drug Info | [6] | |||
| 32 | Imidazo[5,1-c][1,2,4]benzotriazine derivative 3 | Drug Info | [6] | |||
| 33 | Imidazo[5,1-c][1,2,4]benzotriazine derivative 4 | Drug Info | [6] | |||
| 34 | Oxindole derivative 1 | Drug Info | [6] | |||
| 35 | PMID27321640-Compound-58 | Drug Info | [6] | |||
| 36 | PMID27321640-Compound-59 | Drug Info | [6] | |||
| 37 | PMID27321640-Compound-74 | Drug Info | [6] | |||
| 38 | PMID27321640-Compound-75 | Drug Info | [6] | |||
| 39 | PMID27321640-Compound-76 | Drug Info | [6] | |||
| 40 | Purin-6-one derivative 1 | Drug Info | [6] | |||
| 41 | Pyrazolo[3,4-d]pyrimidine derivative 1 | Drug Info | [6] | |||
| 42 | Pyrazolo[3,4-d]pyrimidine derivative 2 | Drug Info | [6] | |||
| 43 | Pyrazolo[3,4-d]pyrimidine derivative 3 | Drug Info | [6] | |||
| 44 | Pyrazolo[3,4-d]pyrimidine derivative 4 | Drug Info | [6] | |||
| 45 | Pyrido[1,2,4]triazolo[4,3-a]pyrazine derivative 1 | Drug Info | [6] | |||
| 46 | Pyrido[1,2,4]triazolo[4,3-a]pyrazine derivative 2 | Drug Info | [6] | |||
| 47 | Pyrido[1,2,4]triazolo[4,3-a]pyrazine derivative 3 | Drug Info | [6] | |||
| 48 | Pyrido[2,3-d]pyrimidine-2,4-diamine derivative 1 | Drug Info | [6] | |||
| 49 | Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 1 | Drug Info | [6] | |||
| 50 | Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 2 | Drug Info | [6] | |||
| 51 | Triazolo-phthalazine derivative 1 | Drug Info | [6] | |||
| 52 | Triazolo-pyridine derivative 2 | Drug Info | [6] | |||
| 53 | Triazolo-pyridine derivative 3 | Drug Info | [6] | |||
| 54 | Triazolo-pyridine derivative 4 | Drug Info | [6] | |||
| 55 | Triazolo-pyridine derivative 5 | Drug Info | [6] | |||
| 56 | Triazolo-pyridine derivative 6 | Drug Info | [6] | |||
| 57 | IMAZODAN | Drug Info | [7] | |||
| 58 | (2R,3S)-3-(6-Amino-purin-9-yl)-nonan-2-ol | Drug Info | [8] | |||
| 59 | 2-Morpholin-4-yl-8-phenylethynyl-chromen-4-one | Drug Info | [9] | |||
| 60 | BAY-60-7550 | Drug Info | [8] | |||
| 61 | Benzyl-(2-pyridin-3-yl-quinazolin-4-yl)-amine | Drug Info | [10] | |||
| 62 | Benzyl-(2-pyridin-4-yl-quinazolin-4-yl)-amine | Drug Info | [10] | |||
| 63 | Cyclic Guanosine Monophosphate | Drug Info | [11] | |||
| 64 | EHNA | Drug Info | [12] | |||
| 65 | isobutylmethylxanthine | Drug Info | [13], [14] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | ND7001 | Drug Info | [4] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "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 | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | Purine metabolism | |||||
| 2 | cGMP-PKG signaling pathway | |||||
| 3 | Morphine addiction | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | TSH Signaling Pathway | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | cGMP effects | |||||
| 2 | G alpha (s) signalling events | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Sulindac and its derivatives: a novel class of anticancer agents. Curr Opin Investig Drugs. 2001 May;2(5):677-83. | |||||
| REF 2 | ClinicalTrials.gov (NCT00060710) CP-461 in the Treatment of Patients With Advanced Melanoma. U.S. National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT00486876) A Study of 3 Doses of Dextofisopam in Females With Irritable Bowel Syndrome. U.S. National Institutes of Health. | |||||
| REF 4 | Phosphodiesterase 2 inhibitors promote axonal outgrowth in organotypic slice co-cultures. Neurosignals. 2013;21(3-4):197-212. | |||||
| REF 5 | The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. J Neural Transm (Vienna). 2010 Nov;117(11):1319-25. | |||||
| REF 6 | Towards selective phosphodiesterase 2A (PDE2A) inhibitors: a patent review (2010 - present).Expert Opin Ther Pat. 2016 Aug;26(8):933-46. | |||||
| REF 7 | Cardiotonic agents. 1. 4,5-Dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3 (2H)-pyridazinones: novel positive inotropic agents for the treatment of conges... J Med Chem. 1984 Sep;27(9):1099-101. | |||||
| REF 8 | The next generation of phosphodiesterase inhibitors: structural clues to ligand and substrate selectivity of phosphodiesterases. J Med Chem. 2005 May 19;48(10):3449-62. | |||||
| REF 9 | PDE2 inhibition by the PI3 kinase inhibitor LY294002 and analogues. Bioorg Med Chem Lett. 2004 Jun 7;14(11):2847-51. | |||||
| REF 10 | Discovery of potent cyclic GMP phosphodiesterase inhibitors. 2-Pyridyl- and 2-imidazolylquinazolines possessing cyclic GMP phosphodiesterase and th... J Med Chem. 1995 Sep 1;38(18):3547-57. | |||||
| REF 11 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 12 | Rapid regulation of PDE-2 and PDE-4 cyclic AMP phosphodiesterase activity following ligation of the T cell antigen receptor on thymocytes: analysis using the selective inhibitors erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA) and rolipram. Cell Signal. 1996 Feb;8(2):97-110. | |||||
| REF 13 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 14 | A new generation of phosphodiesterase inhibitors: multiple molecular forms of phosphodiesterase and the potential for drug selectivity. J Med Chem. 1985 May;28(5):537-45. | |||||
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