2y0j

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Triazoloquinazolines as a novel class of phosphodiesterase 10A (PDE10A) inhibitors, part 2, Lead-optimisation.

Structural highlights

2y0j is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.43Å
Ligands:AXC, MG, ZN
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PDE10_HUMAN Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.[1]

Publication Abstract from PubMed

Novel triazoloquinazolines have been found as phosphodiesterase 10A (PDE10A) inhibitors. Structure-activity studies improved the initial micromolar potency which was found in the lead compound by a 100-fold identifying 5-(1H-benzoimidazol-2-ylmethylsulfanyl)-2-methyl-[1,2,4]triazolo[1,5-c]qui nazoline, 42 (PDE10A IC(50)=12nM) as the most potent compound from the series. Two X-ray structures revealed novel binding modes to the catalytic site of the PDE10A enzyme.

Triazoloquinazolines as a novel class of phosphodiesterase 10A (PDE10A) inhibitors.,Kehler J, Ritzen A, Langgard M, Petersen SL, Farah MM, Bundgaard C, Christoffersen CT, Nielsen J, Kilburn JP Bioorg Med Chem Lett. 2011 Jun 15;21(12):3738-42. Epub 2011 Apr 30. PMID:21602043[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
3 reviews cite this structure
Future directions in phosphodiesterase drug discovery.
DeNinno et al. (2012)
2 more
16 other articles
No citations found

See Also

References

  1. ↑ Wang H, Liu Y, Hou J, Zheng M, Robinson H, Ke H. Structural insight into substrate specificity of phosphodiesterase 10. Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5782-7. Epub 2007 Mar 26. PMID:17389385
  2. ↑ Kehler J, Ritzen A, Langgard M, Petersen SL, Farah MM, Bundgaard C, Christoffersen CT, Nielsen J, Kilburn JP. Triazoloquinazolines as a novel class of phosphodiesterase 10A (PDE10A) inhibitors. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3738-42. Epub 2011 Apr 30. PMID:21602043 doi:10.1016/j.bmcl.2011.04.067

Contents


PDB ID 2y0j

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OCA

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