Target Information
| Target General Information | Top | |||||
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| Target ID |
T39523
(Former ID: TTDI01951)
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| Target Name |
Phosphodiesterase 7A (PDE7A)
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| Synonyms |
TM22; High affinity cAMPspecific 3',5'cyclic phosphodiesterase 7A; High affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A
Click to Show/Hide
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| Gene Name |
PDE7A
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| Target Type |
Discontinued target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Pain [ICD-11: MG30-MG3Z] | |||||
| Function |
May have a role in muscle signal transduction. Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
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| BioChemical Class |
Phosphoric diester hydrolase
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| UniProt ID | ||||||
| EC Number |
EC 3.1.4.53
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| Sequence |
MEVCYQLPVLPLDRPVPQHVLSRRGAISFSSSSALFGCPNPRQLSQRRGAISYDSSDQTA
LYIRMLGDVRVRSRAGFESERRGSHPYIDFRIFHSQSEIEVSVSARNIRRLLSFQRYLRS SRFFRGTAVSNSLNILDDDYNGQAKCMLEKVGNWNFDIFLFDRLTNGNSLVSLTFHLFSL HGLIEYFHLDMMKLRRFLVMIQEDYHSQNPYHNAVHAADVTQAMHCYLKEPKLANSVTPW DILLSLIAAATHDLDHPGVNQPFLIKTNHYLATLYKNTSVLENHHWRSAVGLLRESGLFS HLPLESRQQMETQIGALILATDISRQNEYLSLFRSHLDRGDLCLEDTRHRHLVLQMALKC ADICNPCRTWELSKQWSEKVTEEFFHQGDIEKKYHLGVSPLCDRHTESIANIQIGFMTYL VEPLFTEWARFSNTRLSQTMLGHVGLNKASWKGLQREQSSSEDTDAAFELNSQLLPQENR LS Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | PF-3557156 | Drug Info | Discontinued in Phase 1 | Pain | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | PF-3557156 | Drug Info | [1] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Isobutylmethylxanthine | Ligand Info | |||||
| Structure Description | Multiple Determinants for Inhibitor Selectivity of Cyclic Nucleotide Phosphodiesterases | PDB:1ZKL | ||||
| Method | X-ray diffraction | Resolution | 1.67 Å | Mutation | No | [3] |
| PDB Sequence |
DYNGQAKCML
148 EKVGNWNFDI158 FLFDRLTNGN168 SLVSLTFHLF178 SLHGLIEYFH188 LDMMKLRRFL 198 VMIQEDYHSQ208 NPYHNAVHAA218 DVTQAMHCYL228 KEPKLANSVT238 PWDILLSLIA 248 AATHDLDHPG258 VNQPFLIKTN268 HYLATLYKNT278 SVLENHHWRS288 AVGLLRESGL 298 FSHLPLESRQ308 QMETQIGALI318 LATDISRQNE328 YLSLFRSHLD338 RGDLCLEDTR 348 HRHLVLQMAL358 KCADICNPCR368 TWELSKQWSE378 KVTEEFFHQG388 DIEKKYHLGV 398 SPLCDRHTES408 IANIQIGFMT418 YLVEPLFTEW428 ARFSNTRLSQ438 TMLGHVGLNK 448 ASWKGLQ
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| Ligand Name: 2-(Cyclopentylamino)-3-Ethyl-7-Ethynylthieno[3,2-D]pyrimidin-4(3h)-One | Ligand Info | |||||
| Structure Description | PDE7A catalytic domain in complex with 2-(Cyclopentylamino)thieno[3,2-d]pyrimidin-4(3H)-one derivative | PDB:4PM0 | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [4] |
| PDB Sequence |
DYNGQAKCML
148 EKVGNWNFDI158 FLFDRLTNGN168 SLVSLTFHLF178 SLHGLIEYFH188 LDMMKLRRFL 198 VMIQEDYHSQ208 NPYHNAVHAA218 DVTQAMHCYL228 KEPKLANSVT238 PWDILLSLIA 248 AATHDLDHPG258 VNQPFLIKTN268 HYLATLYKNT278 SVLENHHWRS288 AVGLLRESGL 298 FSHLPLESRQ308 QMETQIGALI318 LATDISRQNE328 YLSLFRSHLD338 RGDLCLEDTR 348 HRHLVLQMAL358 KCADICNPCR368 TWELSKQWSE378 KVTEEFFHQG388 DIEKKYHLGV 398 SPLCDRHTES408 IANIQIGFMT418 YLVEPLFTEW428 ARFSNTRLSQ438 TMLGHVGLNK 448 ASWKGLQR
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Purine metabolism | hsa00230 | Affiliated Target |
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| Class: Metabolism => Nucleotide metabolism | Pathway Hierarchy | ||
| Chemical Structure based Activity Landscape of Target | Top |
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| 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 | [+] 2 KEGG Pathways | + | ||||
| 1 | Purine metabolism | |||||
| 2 | Morphine addiction | |||||
| NetPath Pathway | [+] 3 NetPath Pathways | + | ||||
| 1 | EGFR1 Signaling Pathway | |||||
| 2 | TCR Signaling Pathway | |||||
| 3 | IL2 Signaling Pathway | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | G alpha (s) signalling events | |||||
| WikiPathways | [+] 2 WikiPathways | + | ||||
| 1 | G Protein Signaling Pathways | |||||
| 2 | Ectoderm Differentiation | |||||
| References | Top | |||||
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| REF 1 | Company report (Pfizer pipeline: October 28, 2008) | |||||
| REF 2 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026842) | |||||
| REF 3 | Multiple elements jointly determine inhibitor selectivity of cyclic nucleotide phosphodiesterases 4 and 7. J Biol Chem. 2005 Sep 2;280(35):30949-55. | |||||
| REF 4 | Discovery of 2-(cyclopentylamino)thieno[3,2-d]pyrimidin-4(3H)-one derivatives as a new series of potent phosphodiesterase 7 inhibitors. J Med Chem. 2014 Dec 11;57(23):9844-54. | |||||
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