TAK-063, a PDE10A Inhibitor with Balanced Activation of Direct and Indirect Pathways, Provides Potent Antipsychotic-Like Effects in Multiple Paradigms

Design and synthesis of a novel 2-oxindole scaffold as a highly potent and brain-penetrant phosphodiesterase 10A inhibitor

(2015) Masato Yoshikawa et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Phosphodiesterase 10A Is Tethered to a Synaptic Signaling Complex in Striatum

(2015) Corina Russwurm et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Characterization of the binding properties of T-773 as a PET radioligand for phosphodiesterase 10A

(2015) Akina Harada et al.   NUCLEAR MEDICINE AND BIOLOGY

Characterization of Binding and Inhibitory Properties of TAK-063, a Novel Phosphodiesterase 10A Inhibitor

(2015) Akina Harada et al.   PLoS One

Discovery of 1-[2-Fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (TAK-063), a Highly Potent, Selective, and Orally Active Phosphodiesterase 10A (PDE10A) Inhibitor

(2014) Jun Kunitomo et al.   JOURNAL OF MEDICINAL CHEMISTRY

Interplay of Palmitoylation and Phosphorylation in the Trafficking and Localization of Phosphodiesterase 10A: Implications for the Treatment of Schizophrenia

(2013) E. I. Charych et al.   JOURNAL OF NEUROSCIENCE

The novel phosphodiesterase 10A inhibitor THPP-1 has antipsychotic-like effects in rat and improves cognition in rat and rhesus monkey

(2012) Sean M. Smith et al.   NEUROPHARMACOLOGY

Poster #212 RESULTS OF A PHASE 2A PROOF-OF-CONCEPT TRIAL WITH A PDE10A INHIBITOR IN THE TREATMENT OF ACUTE EXACERBATION OF SCHIZOPHRENIA

(2012) Nicholas DeMartinis et al.   SCHIZOPHRENIA RESEARCH

Potency, selectivity and prolonged binding of saxagliptin to DPP4: maintenance of DPP4 inhibition by saxagliptin in vitro and ex vivo when compared to a rapidly-dissociating DPP4 inhibitor

(2012) Aiying Wang et al.   BMC Pharmacology & Toxicology

Animal models of schizophrenia

(2011) CA Jones et al.   BRITISH JOURNAL OF PHARMACOLOGY

Activation of PDE10 and PDE11 Phosphodiesterases

(2011) Ronald Jäger et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Dopamine D1-like receptor activation depolarizes medium spiny neurons of the mouse nucleus accumbens by inhibiting inwardly rectifying K+ currents through a cAMP-dependent protein kinase A-independent mechanism

(2010) M.V. Podda et al.   NEUROSCIENCE

Discovery of a Novel Class of Phosphodiesterase 10A Inhibitors and Identification of Clinical Candidate 2-[4-(1-Methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline (PF-2545920) for the Treatment of Schizophrenia†† Coordinates of the PDE10A crystal structures have been deposited in the Protein Data Bank for compound 1 (3HQW), 2 (3HQY), 3 (3HQW) and 9 (3HR1).

(2009) Patrick R. Verhoest et al.   JOURNAL OF MEDICINAL CHEMISTRY

Phosphodiesterase 10A Inhibitor Activity in Preclinical Models of the Positive, Cognitive, and Negative Symptoms of Schizophrenia

(2009) S. M. Grauer et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Increased social interaction in mice deficient of the striatal medium spiny neuron-specific phosphodiesterase 10A2

(2008) Hiromi Sano et al.   JOURNAL OF NEUROCHEMISTRY

Distinct Roles of PDE4 and PDE10A in the Regulation of cAMP/PKA Signaling in the Striatum

(2008) A. Nishi et al.   JOURNAL OF NEUROSCIENCE

Preclinical Characterization of Selective Phosphodiesterase 10A Inhibitors: A New Therapeutic Approach to the Treatment of Schizophrenia

(2008) C. J. Schmidt et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS