5C29: Pde10 Complexed With 6-chloro-2-cyclopropyl-5-methyl-n-propyl- Pyrimidin-4-amine

Citation:
Abstract
Screening of a fragment library for PDE10A inhibitors identified a low molecular weight pyrimidine hit with PDE10A Ki of 8700 nM and LE of 0.59. Initial optimization by catalog followed by iterative parallel synthesis guided by X-ray cocrystal structures resulted in rapid potency improvements with minimal loss of ligand efficiency. Compound 15h, with PDE10A Ki of 8.2 pM, LE of 0.49, and >5000-fold selectivity over other PDEs, fully attenuates MK-801-induced hyperlocomotor activity after ip dosing.
PDB ID: 5C29Download
MMDB ID: 133133
PDB Deposition Date: 2015/6/15
Updated in MMDB: 2015/10
Experimental Method:
x-ray diffraction
Resolution: 2.05  Å
Source Organism:
Similar Structures:
Biological Unit for 5C29: monomeric; determined by author and by software (PISA)
Molecular Components in 5C29
Label Count Molecule
Protein (1 molecule)
1
Camp and Camp-inhibited Cgmp 3',5'-cyclic Phosphodiesterase 10A(Gene symbol: PDE10A)
Molecule annotation
Chemicals (3 molecules)
1
1
2
1
3
1
* Click molecule labels to explore molecular sequence information.

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