mardepodect   Click here for help

GtoPdb Ligand ID: 9617

Synonyms: MP-10 | PF-02545920 | PF-2545920 | PF2545920 | pyrazole 9 [PMID: 19630403]
PDB Ligand
Compound class: Synthetic organic
Comment: Mardepodect (PF-2545920) is a selective, orally active inhibitor of phosphodiesterase (PDE) 10A [3]. Identified using structure-based drug design, the compound is optimised for selectivity, brain penetration and drug-like properties. PF-2545920 is the first PDE10A inhibitor identified as a clinical lead utilizing this mechanism for the treatment of schizophrenia.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 3
Hydrogen bond donors 0
Rotatable bonds 5
Topological polar surface area 52.83
Molecular weight 392.16
XLogP 4.88
No. Lipinski's rules broken 0
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Canonical SMILES Cn1nc(c(c1)c1ccncc1)c1ccc(cc1)OCc1ccc2c(n1)cccc2
Isomeric SMILES Cn1nc(c(c1)c1ccncc1)c1ccc(cc1)OCc1ccc2c(n1)cccc2
InChI InChI=1S/C25H20N4O/c1-29-16-23(18-12-14-26-15-13-18)25(28-29)20-7-10-22(11-8-20)30-17-21-9-6-19-4-2-3-5-24(19)27-21/h2-16H,17H2,1H3
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Summary of Clinical Use Click here for help
PF-2545920 progressed to Phase 2 clinical trials for schizophrenia (NCT01939548), however evaluation in this indication has been terminated as a pre-planned interim analysis indicated the trial was unlikely to meet its pre-specified efficacy criteria. Termination was not linked to any safety concerns. Phase 2 evaluation in Huntington's disease has also been terminated (NCT02342548).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
PDE10A inhibition is predicted to regulate cyclic nucleotide signaling in the corticostriatothalamic circuit, with antipsychotic effect.