Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTJW4LU)

• DTT Name: Phosphodiesterase 10A (PDE10)
• Synonyms: cAMP and cAMPinhibited cGMP 3',5'cyclic phosphodiesterase 10A; cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A
• Gene Name: PDE10A
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Phosphoric diester hydrolase
• UniProt ID: PDE10_HUMAN
• TTD ID: T84133
• EC Number: EC 3.1.4.17
• Sequence:
  MRIEERKSQHLTGLTDEKVKAYLSLHPQVLDEFVSESVSAETVEKWLKRKNNKSEDESAP
  KEVSRYQDTNMQGVVYELNSYIEQRLDTGGDNQLLLYELSSIIKIATKADGFALYFLGEC
  NNSLCIFTPPGIKEGKPRLIPAGPITQGTTVSAYVAKSRKTLLVEDILGDERFPRGTGLE
  SGTRIQSVLCLPIVTAIGDLIGILELYRHWGKEAFCLSHQEVATANLAWASVAIHQVQVC
  RGLAKQTELNDFLLDVSKTYFDNIVAIDSLLEHIMIYAKNLVNADRCALFQVDHKNKELY
  SDLFDIGEEKEGKPVFKKTKEIRFSIEKGIAGQVARTGEVLNIPDAYADPRFNREVDLYT
  GYTTRNILCMPIVSRGSVIGVVQMVNKISGSAFSKTDENNFKMFAVFCALALHCANMYHR
  IRHSECIYRVTMEKLSYHSICTSEEWQGLMQFTLPVRLCKEIELFHFDIGPFENMWPGIF
  VYMVHRSCGTSCFELEKLCRFIMSVKKNYRRVPYHNWKHAVTVAHCMYAILQNNHTLFTD
  LERKGLLIACLCHDLDHRGFSNSYLQKFDHPLAALYSTSTMEQHHFSQTVSILQLEGHNI
  FSTLSSSEYEQVLEIIRKAIIATDLALYFGNRKQLEEMYQTGSLNLNNQSHRDRVIGLMM
  TACDLCSVTKLWPVTKLTANDIYAEFWAEGDEMKKLGIQPIPMMDRDKKDEVPQGQLGFY
  NAVAIPCYTTLTQILPPTEPLLKACRDNLSQWEKVIRGEETATWISSPSVAQKAAASED
• 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.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Morphine addiction (hsa05032)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  cGMP effects (R-HSA-418457)

Molecular Interaction Atlas (MIA) of This DTT

9 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lu AF11167	DMJOYNZ	Schizophrenia	6A20	Phase 2	[2]
OMS824	DMA4OGL	Huntington disease	8A01.10	Phase 2	[1]
PF-02545920	DMJPE61	Huntington disease	8A01.10	Phase 2	[3]
TAK-063	DMP1873	Schizophrenia	6A20	Phase 2	[4]
Tofisopam	DMTGNWU	Hyperuricaemia	5C55.Y	Phase 2	[5]
FRM-6308	DMNCOE1	Schizophrenia	6A20	Phase 1b	[6]
AMG 579	DMRMC7U	Schizophrenia	6A20	Phase 1	[7]
PBF-999	DMBSQH9	Huntington disease	8A01.10	Phase 1	[8]
RG7203	DMYX4NP	Schizophrenia	6A20	Phase 1	[9]

31 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1,2,4-triazole [4,3-a]quinoxaline derivative 1	DMD9QW2	N. A.	N. A.	Patented	[10]
1,2,4-triazole [4,3-a]quinoxaline derivative 2	DM3DIW9	N. A.	N. A.	Patented	[10]
1,2,4-triazole [4,3-a]quinoxaline derivative 3	DMKXRYM	N. A.	N. A.	Patented	[10]
1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]quinoxaline derivative 3	DM62K40	N. A.	N. A.	Patented	[10]
1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]quinoxaline derivative 4	DMQSTG9	N. A.	N. A.	Patented	[10]
1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]quinoxaline derivative 5	DM9E0ZD	N. A.	N. A.	Patented	[10]
1-aryl-4-methyl-[1,2,4]triazolo[4,3-a]quinoxaline derivative 6	DM826JW	N. A.	N. A.	Patented	[10]
Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 1	DMQBH81	N. A.	N. A.	Patented	[10]
Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 2	DMS3ROL	N. A.	N. A.	Patented	[10]
Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 3	DMZ61T8	N. A.	N. A.	Patented	[10]
Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 4	DMKR5ZO	N. A.	N. A.	Patented	[10]
Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 5	DM7UAKH	N. A.	N. A.	Patented	[10]
Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 6	DMKRUAN	N. A.	N. A.	Patented	[10]
Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 7	DMINBJM	N. A.	N. A.	Patented	[10]
Imidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine derivative 8	DM42EST	N. A.	N. A.	Patented	[10]
Imidazo[5,1-c][1,2,4]benzotriazine derivative 1	DMUB4QL	N. A.	N. A.	Patented	[10]
Imidazo[5,1-c][1,2,4]benzotriazine derivative 2	DMB8AJP	N. A.	N. A.	Patented	[10]
Imidazo[5,1-c][1,2,4]benzotriazine derivative 3	DMYX684	N. A.	N. A.	Patented	[10]
Imidazo[5,1-c][1,2,4]benzotriazine derivative 4	DMWF4S7	N. A.	N. A.	Patented	[10]
PMID27321640-Compound-58	DM0NYK3	N. A.	N. A.	Patented	[10]
PMID27321640-Compound-59	DM41B5O	N. A.	N. A.	Patented	[10]
Pyrido[1,2,4]triazolo[4,3-a]pyrazine derivative 1	DMHKRVL	N. A.	N. A.	Patented	[10]
Pyrido[1,2,4]triazolo[4,3-a]pyrazine derivative 2	DMUO25Y	N. A.	N. A.	Patented	[10]
Pyrido[1,2,4]triazolo[4,3-a]pyrazine derivative 3	DMAEYNT	N. A.	N. A.	Patented	[10]
Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 1	DMC8935	N. A.	N. A.	Patented	[10]
Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 2	DM4CSBD	N. A.	N. A.	Patented	[10]
Triazolo-pyridine derivative 2	DMXPQ24	N. A.	N. A.	Patented	[10]
Triazolo-pyridine derivative 3	DMQL1TV	N. A.	N. A.	Patented	[10]
Triazolo-pyridine derivative 4	DM5ZQKS	N. A.	N. A.	Patented	[10]
Triazolo-pyridine derivative 5	DM1R205	N. A.	N. A.	Patented	[10]
Triazolo-pyridine derivative 6	DMX4WFP	N. A.	N. A.	Patented	[10]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Schizophrenia	6A20	Pre-frontal cortex	1.99E-01	-0.07	-0.21
Schizophrenia	6A20	Superior temporal cortex	4.51E-01	-0.05	-0.32

References

• [1] New Drugs/Drug News. P T. 2013 November; 38(11): 667-672.
• [2] PDE10A Inhibitors-Clinical Failure or Window Into Antipsychotic Drug Action?. Front Neurosci. 2021 Jan 20;14:600178.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Characterization of Binding and Inhibitory Properties of TAK-063, a Novel Phosphodiesterase 10A Inhibitor. PLoS One. 2015; 10(3): e0122197.
• [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.
• [6] Massive schizophrenia genomics study offers new drug directions. Nat Rev Drug Discov. 2014 Sep;13(9):641-2.
• [7] 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.
• [8] Clinical pipeline report, company report or official report of Palobiofarma.
• [9] Synaptic synopsis. SciBX 6(41); doi:10.1038/scibx.2013.1153. Oct. 24, 2013
• [10] Towards selective phosphodiesterase 2A (PDE2A) inhibitors: a patent review (2010 - present).Expert Opin Ther Pat. 2016 Aug;26(8):933-46.