Target Information
| Target General Information | Top | |||||
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| Target ID |
T84133
(Former ID: TTDNC00456)
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| Target Name |
Phosphodiesterase 10A (PDE10)
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| Synonyms |
cAMP and cAMPinhibited cGMP 3',5'cyclic phosphodiesterase 10A; cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
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| Gene Name |
PDE10A
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 5 Target-related Diseases | + | ||||
| 1 | Choreiform disorder [ICD-11: 8A01] | |||||
| 2 | Inborn purine/pyrimidine/nucleotide metabolism error [ICD-11: 5C55] | |||||
| 3 | Irritable bowel syndrome [ICD-11: DD91] | |||||
| 4 | Schizophrenia [ICD-11: 6A20] | |||||
| 5 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
| Function |
Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate. May play a critical role in regulating cAMP and cGMP levels in the striatum, a region of the brain that contributes to the control of movement and cognition. Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides.
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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 |
MRIEERKSQHLTGLTDEKVKAYLSLHPQVLDEFVSESVSAETVEKWLKRKNNKSEDESAP
KEVSRYQDTNMQGVVYELNSYIEQRLDTGGDNQLLLYELSSIIKIATKADGFALYFLGEC NNSLCIFTPPGIKEGKPRLIPAGPITQGTTVSAYVAKSRKTLLVEDILGDERFPRGTGLE SGTRIQSVLCLPIVTAIGDLIGILELYRHWGKEAFCLSHQEVATANLAWASVAIHQVQVC RGLAKQTELNDFLLDVSKTYFDNIVAIDSLLEHIMIYAKNLVNADRCALFQVDHKNKELY SDLFDIGEEKEGKPVFKKTKEIRFSIEKGIAGQVARTGEVLNIPDAYADPRFNREVDLYT GYTTRNILCMPIVSRGSVIGVVQMVNKISGSAFSKTDENNFKMFAVFCALALHCANMYHR IRHSECIYRVTMEKLSYHSICTSEEWQGLMQFTLPVRLCKEIELFHFDIGPFENMWPGIF VYMVHRSCGTSCFELEKLCRFIMSVKKNYRRVPYHNWKHAVTVAHCMYAILQNNHTLFTD LERKGLLIACLCHDLDHRGFSNSYLQKFDHPLAALYSTSTMEQHHFSQTVSILQLEGHNI FSTLSSSEYEQVLEIIRKAIIATDLALYFGNRKQLEEMYQTGSLNLNNQSHRDRVIGLMM TACDLCSVTKLWPVTKLTANDIYAEFWAEGDEMKKLGIQPIPMMDRDKKDEVPQGQLGFY NAVAIPCYTTLTQILPPTEPLLKACRDNLSQWEKVIRGEETATWISSPSVAQKAAASED Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T38G6P | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 9 Clinical Trial Drugs | + | ||||
| 1 | Lu AF11167 | Drug Info | Phase 2 | Schizophrenia | [2] | |
| 2 | OMS824 | Drug Info | Phase 2 | Huntington disease | [3] | |
| 3 | PF-02545920 | Drug Info | Phase 2 | Schizophrenia | [4] | |
| 4 | TAK-063 | Drug Info | Phase 2 | Schizophrenia | [5] | |
| 5 | Tofisopam | Drug Info | Phase 2 | Irritable bowel syndrome | [6] | |
| 6 | FRM-6308 | Drug Info | Phase 1b | Schizophrenia | [7] | |
| 7 | AMG 579 | Drug Info | Phase 1 | Schizophrenia | [8] | |
| 8 | PBF-999 | Drug Info | Phase 1 | Solid tumour/cancer | [9] | |
| 9 | RG7203 | Drug Info | Phase 1 | Schizophrenia | [10] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 40 Inhibitor drugs | + | ||||
| 1 | Lu AF11167 | Drug Info | [11] | |||
| 2 | OMS824 | Drug Info | [1] | |||
| 3 | PF-02545920 | Drug Info | [12] | |||
| 4 | TAK-063 | Drug Info | [13] | |||
| 5 | Tofisopam | Drug Info | [14] | |||
| 6 | FRM-6308 | Drug Info | [15] | |||
| 7 | AMG 579 | Drug Info | [16] | |||
| 8 | PBF-999 | Drug Info | [17] | |||
| 9 | RG7203 | Drug Info | [18] | |||
| 10 | 1,2,4-triazole [4,3-a]quinoxaline derivative 1 | Drug Info | [19] | |||
| 11 | 1,2,4-triazole [4,3-a]quinoxaline derivative 2 | Drug Info | [19] | |||
| 12 | 1,2,4-triazole [4,3-a]quinoxaline derivative 3 | Drug Info | [19] | |||
| 13 | 1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]quinoxaline derivative 3 | Drug Info | [19] | |||
| 14 | 1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]quinoxaline derivative 4 | Drug Info | [19] | |||
| 15 | 1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]quinoxaline derivative 5 | Drug Info | [19] | |||
| 16 | 1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]quinoxaline derivative 6 | Drug Info | [19] | |||
| 17 | Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 1 | Drug Info | [19] | |||
| 18 | Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 2 | Drug Info | [19] | |||
| 19 | Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 3 | Drug Info | [19] | |||
| 20 | Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 4 | Drug Info | [19] | |||
| 21 | Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 5 | Drug Info | [19] | |||
| 22 | Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 6 | Drug Info | [19] | |||
| 23 | Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 7 | Drug Info | [19] | |||
| 24 | Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 8 | Drug Info | [19] | |||
| 25 | Imidazo[5,1-c][1,2,4]benzotriazine derivative 1 | Drug Info | [19] | |||
| 26 | Imidazo[5,1-c][1,2,4]benzotriazine derivative 2 | Drug Info | [19] | |||
| 27 | Imidazo[5,1-c][1,2,4]benzotriazine derivative 3 | Drug Info | [19] | |||
| 28 | Imidazo[5,1-c][1,2,4]benzotriazine derivative 4 | Drug Info | [19] | |||
| 29 | PMID27321640-Compound-58 | Drug Info | [19] | |||
| 30 | PMID27321640-Compound-59 | Drug Info | [19] | |||
| 31 | Pyrido[1,2,4]triazolo[4,3-a]pyrazine derivative 1 | Drug Info | [19] | |||
| 32 | Pyrido[1,2,4]triazolo[4,3-a]pyrazine derivative 2 | Drug Info | [19] | |||
| 33 | Pyrido[1,2,4]triazolo[4,3-a]pyrazine derivative 3 | Drug Info | [19] | |||
| 34 | Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 1 | Drug Info | [19] | |||
| 35 | Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 2 | Drug Info | [19] | |||
| 36 | Triazolo-pyridine derivative 2 | Drug Info | [19] | |||
| 37 | Triazolo-pyridine derivative 3 | Drug Info | [19] | |||
| 38 | Triazolo-pyridine derivative 4 | Drug Info | [19] | |||
| 39 | Triazolo-pyridine derivative 5 | Drug Info | [19] | |||
| 40 | Triazolo-pyridine derivative 6 | Drug Info | [19] | |||
| 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 Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Purine metabolism | |||||
| 2 | Morphine addiction | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Purine Metabolism | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | cGMP effects | |||||
| 2 | G alpha (s) signalling events | |||||
| References | Top | |||||
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| REF 1 | New Drugs/Drug News. P T. 2013 November; 38(11): 667-672. | |||||
| REF 2 | ClinicalTrials.gov (NCT03929497) Flexible-dose Long-term Extension Study of Lu AF11167 in Patients With Schizophrenia With Prominent Negative Symptoms. U.S. National Institutes of Health. | |||||
| REF 3 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025042) | |||||
| REF 4 | ClinicalTrials.gov (NCT01939548) An Outpatient Study Of The Efficacy, Safety, And Tolerability Of PF-02545920 In The Adjunctive Treatment Of Sub-Optimally Controlled Symptoms of Schizophrenia. U.S. National Institutes of Health. | |||||
| REF 5 | ClinicalTrials.gov (NCT02477020) A Phase 2 Efficacy and Safety Study of TAK-063 in Participants With an Acute Exacerbation of Schizophrenia. | |||||
| REF 6 | ClinicalTrials.gov (NCT00486876) A Study of 3 Doses of Dextofisopam in Females With Irritable Bowel Syndrome. U.S. National Institutes of Health. | |||||
| REF 7 | Clinical pipeline report, company report or official report of Forum pharmaceuticals. | |||||
| REF 8 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800035904) | |||||
| REF 9 | ClinicalTrials.gov (NCT03786484) Study of PBF-999 in Solid Tumour Advanced Cancer. U.S. National Institutes of Health. | |||||
| REF 10 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 11 | PDE10A Inhibitors-Clinical Failure or Window Into Antipsychotic Drug Action?. Front Neurosci. 2021 Jan 20;14:600178. | |||||
| REF 12 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 13 | Characterization of Binding and Inhibitory Properties of TAK-063, a Novel Phosphodiesterase 10A Inhibitor. PLoS One. 2015; 10(3): e0122197. | |||||
| REF 14 | 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 15 | Massive schizophrenia genomics study offers new drug directions. Nat Rev Drug Discov. 2014 Sep;13(9):641-2. | |||||
| REF 16 | Discovery of clinical candidate 1-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone (AMG 579), a potent, selective, and efficacious inhibitor of phosphodiesterase10A (PDE10A). J Med Chem. 2014 Aug 14;57(15):6632-41. | |||||
| REF 17 | Clinical pipeline report, company report or official report of Palobiofarma. | |||||
| REF 18 | Synaptic synopsis. SciBX 6(41); doi:10.1038/scibx.2013.1153. Oct. 24, 2013 | |||||
| REF 19 | Towards selective phosphodiesterase 2A (PDE2A) inhibitors: a patent review (2010 - present).Expert Opin Ther Pat. 2016 Aug;26(8):933-46. | |||||
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