Target Binding Site Detail
| Target General Information | Top | ||||
|---|---|---|---|---|---|
| Target ID | T84133 | Target Info | |||
| Target Name | Phosphodiesterase 10A (PDE10) | ||||
| Synonyms | cAMP and cAMPinhibited cGMP 3',5'cyclic phosphodiesterase 10A; cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A | ||||
| Target Type | Clinical trial Target | ||||
| Gene Name | PDE10A | ||||
| Biochemical Class | Phosphoric diester hydrolase | ||||
| UniProt ID | |||||
| Ligand General Information | Top | ||||
|---|---|---|---|---|---|
| Ligand Name | 3-(1-Hydroxy-2-Methylpropan-2-Yl)-5-Phenyl-3,5-Dihydro-1h-Imidazo[4,5-C][1,8]naphthyridine-2,4-Dione | Ligand Info | |||
| Canonical SMILES | CC(C)(CO)N1C2=C(C3=C(N=CC=C3)N(C2=O)C4=CC=CC=C4)NC1=O | ||||
| InChI | 1S/C19H18N4O3/c1-19(2,11-24)23-15-14(21-18(23)26)13-9-6-10-20-16(13)22(17(15)25)12-7-4-3-5-8-12/h3-10,24H,11H2,1-2H3,(H,21,26) | ||||
| InChIKey | ZQRNBXXBVMUYDO-UHFFFAOYSA-N | ||||
| PubChem Compound ID | 91826676 | ||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| PDB ID: 5C2H PDE10 complexed with 6-chloro-N-[(2,4-dimethylthiazol-5-yl)methyl]-5-methyl-2-[3-(2-quinolyl)propoxy]pyrimidin-4-amine | ||||||
| Method | X-ray diffraction | Resolution | 2.09 Å | Mutation | No | [1] |
| PDB Sequence |
QFTLPVRLCK
460 EIELFHFDIG470 PFENMWPGIF480 VYMVHRSCGT490 SCFELEKLCR500 FIMSVKKNYR 510 RVPYHNWKHA520 VTVAHCMYAI530 LQNNHTLFTD540 LERKGLLIAC550 LCHDLDHRGF 560 SNSYLQKFDH570 PLAALYSTST580 MEQHHFSQTV590 SILQLEGHNI600 FSTLSSSEYE 610 QVLEIIRKAI620 IATDLALYFG630 NRKQLEEMYQ640 TGSLNLNNQS650 HRDRVIGLMM 660 TACDLCSVTK670 LWPVTKLTAN680 DIYAEFWAEG690 DEMKKLGIQP700 IPMMDRDKKD 710 EVPQGQLGFY720 NAVAIPCYTT730 LTQILPPTEP740 LLKACRDNLS750 QWEKVIRG |
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| PDB ID: 5C2E PDE10 complexed with6-chloro-N-[(2,4-dimethylthiazol-5-yl)methyl]-5-methyl-2-[2-(2-pyridyl)ethoxy]pyrimidin-4-amine | ||||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [1] |
| PDB Sequence |
HMSICTSEEW
446 QGLMQFTLPV456 RLCKEIELFH466 FDIGPFENMW476 PGIFVYMVHR486 SCGTSCFELE 496 KLCRFIMSVK506 KNYRRVPYHN516 WKHAVTVAHC526 MYAILQNNHT536 LFTDLERKGL 546 LIACLCHDLD556 HRGFSNSYLQ566 KFDHPLAALY576 STSTMEQHHF586 SQTVSILQLE 596 GHNIFSTLSS606 SEYEQVLEII616 RKAIIATDLA626 LYFGNRKQLE636 EMYQTGSLNL 646 NNQSHRDRVI656 GLMMTACDLC666 SVTKLWPVTK676 LTANDIYAEF686 WAEGDEMKKL 696 GIQPIPMMDR706 DKKDEVPQGQ716 LGFYNAVAIP726 CYTTLTQILP736 PTEPLLKACR 746 DNLSQWEKVI756 RGE
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| PDB ID: 5DH4 PDE10 complexed with 5-chloro-N-[(2,4-dimethylthiazol-5-yl)methyl]pyrazolo[1,5-a]pyrimidin-7-amine | ||||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | No | [2] |
| PDB Sequence |
QFTLPVRLCK
460 EIELFHFDIG470 PFENMWPGIF480 VYMVHRSCGT490 SCFELEKLCR500 FIMSVKKNYR 510 RVPYHNWKHA520 VTVAHCMYAI530 LQNNHTLFTD540 LERKGLLIAC550 LCHDLDHRGF 560 SNSYLQKFDH570 PLAALYSTST580 MEQHHFSQTV590 SILQLEGHNI600 FSTLSSSEYE 610 QVLEIIRKAI620 IATDLALYFG630 NRKQLEEMYQ640 TGSLNLNNQS650 HRDRVIGLMM 660 TACDLCSVTK670 LWPVTKLTAN680 DIYAEFWAEG690 DEMKKLGIQP700 IPMMDRDKKD 710 EVPQGQLGFY720 NAVAIPCYTT730 LTQILPPTEP740 LLKACRDNLS750 QWEKVIR |
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| PDB ID: 4ZO5 PDE10 complexed with 4-isopropoxy-2-(2-(3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)isoindoline-1,3-dione | ||||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [3] |
| PDB Sequence |
HMSICTSEEW
446 QGLMQFTLPV456 RLCKEIELFH466 FDIGPFENMW476 PGIFVYMVHR486 SCGTSCFELE 496 KLCRFIMSVK506 KNYRRVPYHN516 WKHAVTVAHC526 MYAILQNNHT536 LFTDLERKGL 546 LIACLCHDLD556 HRGFSNSYLQ566 KFDHPLAALY576 STSTMEQHHF586 SQTVSILQLE 596 GHNIFSTLSS606 SEYEQVLEII616 RKAIIATDLA626 LYFGNRKQLE636 EMYQTGSLNL 646 NNQSHRDRVI656 GLMMTACDLC666 SVTKLWPVTK676 LTANDIYAEF686 WAEGDEMKKL 696 GIQPIPMMDR706 DKKDEVPQGQ716 LGFYNAVAIP726 CYTTLTQILP736 PTEPLLKACR 746 DNLSQWEKVI756 RGE
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Click to Show 3D Structure of This Binding Site
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| References | Top | ||||
|---|---|---|---|---|---|
| REF 1 | Discovery and Optimization of a Series of Pyrimidine-Based Phosphodiesterase 10A (PDE10A) Inhibitors through Fragment Screening, Structure-Based Design, and Parallel Synthesis. J Med Chem. 2015 Oct 8;58(19):7888-94. | ||||
| REF 2 | Discovery of pyrazolopyrimidine phosphodiesterase 10A inhibitors for the treatment of schizophrenia. Bioorg Med Chem Lett. 2016 Jan 1;26(1):126-32. | ||||
| REF 3 | Discovery of [??C]MK-8193 as a PET tracer to measure target engagement of phosphodiesterase 10A (PDE10A) inhibitors. Bioorg Med Chem Lett. 2015 Nov 1;25(21):4893-4898. | ||||
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