title: AMG 580: a novel small molecule phosphodiesterase 10A (PDE10A) positron emission tomography tracer.
abstract: Phosphodiesterase 10A (PDE10A) inhibitors have therapeutic potential for the treatment of psychiatric and neurologic disorders, such as schizophrenia and Huntington's disease. One of the key requirements for successful central nervous system drug development is to demonstrate target coverage of therapeutic candidates in brain for lead optimization in the drug discovery phase and for assisting dose selection in clinical development. Therefore, we identified AMG 580 [1-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)-2-fluoropropan-1-one], a novel, selective small-molecule antagonist with subnanomolar affinity for rat, primate, and human PDE10A. We showed that AMG 580 is suitable as a tracer for lead optimization to determine target coverage by novel PDE10A inhibitors using triple-stage quadrupole liquid chromatography-tandem mass spectrometry technology. [(3)H]AMG 580 bound with high affinity in a specific and saturable manner to both striatal homogenates and brain slices from rats, baboons, and human in vitro. Moreover, [(18)F]AMG 580 demonstrated prominent uptake by positron emission tomography in rats, suggesting that radiolabeled AMG 580 may be suitable for further development as a noninvasive radiotracer for target coverage measurements in clinical studies. These results indicate that AMG 580 is a potential imaging biomarker for mapping PDE10A distribution and ensuring target coverage by therapeutic PDE10A inhibitors in clinical studies.
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.) hangc@amgen.com.
authors.forename: Hang
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Dianna
authors.initials: D
authors.lastname: Lester-Zeiner
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Jianxia
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Silke
authors.initials: S
authors.lastname: Miller
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Charlie
authors.initials: C
authors.lastname: Glaus
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Essa
authors.initials: E
authors.lastname: Hu
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Ning
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Jessica
authors.initials: J
authors.lastname: Able
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Christopher
authors.initials: C
authors.lastname: Biorn
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Jamie
authors.initials: J
authors.lastname: Wong
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Ji
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Klaus
authors.initials: K
authors.lastname: Michelsen
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Geraldine
authors.initials: G
authors.lastname: Hill Della Puppa
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Tim
authors.initials: T
authors.lastname: Kazules
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Hui Hannah
authors.initials: HH
authors.lastname: Dou
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Santosh
authors.initials: S
authors.lastname: Talreja
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Ada
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Shannon
authors.initials: S
authors.lastname: Rumfelt
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Roxanne K
authors.initials: RK
authors.lastname: Kunz
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Hu
authors.initials: H
authors.lastname: Ye
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Oliver R
authors.initials: OR
authors.lastname: Thiel
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Toni
authors.initials: T
authors.lastname: Williamson
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Carl
authors.initials: C
authors.lastname: Davis
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Amy
authors.initials: A
authors.lastname: Porter
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: David
authors.initials: D
authors.lastname: Immke
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Allen
authors.affiliation: Department of Neuroscience (H.C., D.L.-Z., J.A., C.B., H.H.D., S.T., A.P.), Department of Pharmacokinetics and Drug Metabolism (J.S., J.W., J.M.), and Department of Molecular Structures and Characterization (X.Z., A.C.), Amgen Inc., South San Francisco, California; Department of Neuroscience (S.M., G.H.D.P., D.I., J.T.), Department of Pharmacokinetics and Drug Metabolism (C.D.), Research Imaging Sciences (C.G., T.K., H.Y.), Department of Small Molecule Chemistry (E.H., N.C., S.R., R.K.K., J.R.A.), and Department of Process Development (O.R.T.), Amgen Inc., Thousand Oaks, California; and Department of Molecular Structures and Characterization (K.M.) and Department of Discovery Toxicology (T.W.), Amgen Inc., Cambridge, Massachusetts (K.M.).
authors.forename: James
authors.initials: J
authors.lastname: Treanor
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D001921:Brain / Q000000981:diagnostic imaging / Q000201:enzymology*; D002853:Chromatography, Liquid; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D015394:Molecular Structure; D010215:Papio; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D011719:Pyrazines / Q000493:pharmacokinetics / Q000494:pharmacology*; D011869:Radioligand Assay; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013237:Stereoisomerism; D020349:Surface Plasmon Resonance; D014018:Tissue Distribution
chemical_list: C000596178:1-(4-(3-(4-(1H-benzo(d)imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)-2-fluoropropan-1-one; D001562:Benzimidazoles; D005462:Fluorine Radioisotopes; D010726:Phosphodiesterase Inhibitors; D011719:Pyrazines; C119843:PDE10A protein, human; C512064:PDE10A protein, rat; D010727:Phosphoric Diester Hydrolases