5k9r

From Proteopedia

PDE10a with imidazopyrazine inhibitor

Structural highlights

5k9r 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 2.7Å
Ligands:	, ,
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

Design and optimization of a novel series of imidazo[1,2-b]pyridazine PDE10a inhibitors are described. Compound 31 displays excellent pharmacokinetic properties and was also evaluated as an insulin secretagogue in vitro and in vivo.

Discovery of novel potent imidazo[1,2-b]pyridazine PDE10a inhibitors.,Meegalla SK, Huang H, Illig CR, Parks DJ, Chen J, Lee YK, Wilson KJ, Patel SK, Cheung WS, Lu T, Kirchner T, Askari HB, Geisler J, Patch RJ, Gibbs AC, Rady B, Connelly M, Player MR Bioorg Med Chem Lett. 2016 Sep 1;26(17):4216-22. doi: 10.1016/j.bmcl.2016.07.054., Epub 2016 Jul 25. PMID:27491708^[2]

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

References

↑ 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
↑ Meegalla SK, Huang H, Illig CR, Parks DJ, Chen J, Lee YK, Wilson KJ, Patel SK, Cheung WS, Lu T, Kirchner T, Askari HB, Geisler J, Patch RJ, Gibbs AC, Rady B, Connelly M, Player MR. Discovery of novel potent imidazo[1,2-b]pyridazine PDE10a inhibitors. Bioorg Med Chem Lett. 2016 Sep 1;26(17):4216-22. doi: 10.1016/j.bmcl.2016.07.054., Epub 2016 Jul 25. PMID:27491708 doi:http://dx.doi.org/10.1016/j.bmcl.2016.07.054