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    Pomaglumetad (LY404039)
    Pomaglumetad (LY404039)

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V1079
    CAS #: 635318-11-5 Purity ≥98%

    Description: Pomaglumetad (LY404039; LY-404039; LY-404,039; LY404,039) is a novel and potent agonist of recombinant human mGlu2/mGlu3 receptors with the potential for the treatment of Schizophrenia. It activates mGlu2/mGlu3 receptors with Ki values of 149 nM/92 nM, and exhibits >100-fold selectivity for mGlu2/mGlu3 over ionotropic glutamate receptors, glutamate transporters, and other receptors. The inhibition of forskolin-stimulated cAMP formation has indicated that LY404039 was a nanomolar potent agonist of human mGlu2 (EC50 = 23 nM) and mGlu3 (EC50 = 48 nM) receptors.

    References: J Pharmacol Exp Ther. 2007 Apr;321(1):308-17; J Pharmacol Exp Ther. 2008 Jul;326(1):209-17; Behav Brain Res. 2006 Aug 10;171(2):207-15. 

    Related CAS#: 635318-26-2 (Pomaglumetad methionil HCl; LY2140023; prodrug of LY-404039); 635318-55-7 (Pomaglumetad methionil free base); 635318-56-8 (Pomaglumetad methionil tosylate); 635318-57-9; (Pomaglumetad methionil mseylate); 956385-05-0 (Pomaglumetad methionil hydrate) 

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    Molecular Weight (MW)235.22
    CAS No.635318-11-5 (LY404039; Pomaglumetad); 
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 1 mg/mL (4.3 mM)
    Water: <1 mg/mL
    Ethanol: <1 mg/mL
    Solubility (In vivo)30% propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL
    SynonymsLY-404039; LY 404039; Pomaglumetad; LY404039; LY-404,039; LY404,039; LY 404,039 

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    In Vitro

    In vitro activity: LY404039 exhibits low binding affinity to group III mGlu receptors including mGlu6, mGlu7 and mGlu8 with a Ki value more than 5 μM. LY404039 shows little affinity for ionotropic glutamate receptors, glutamate transporter subtypes, monoamine and other receptors. LY404039 potently inhibits forskolin-stimulated cAMP formation in cells expressing human mGlu2 and mGlu3 receptors. LY404039 suppresses electrically evoked excitatory activity in the striatum, and serotonin-induced L-glutamate release in the prefrontal cortex. LY404039 could modulate glutamatergic activity in limbic and forebrain areas relevant to psychiatric disorders and may be devoid of negative side effects associated with current antipsychotics and anxiolytics. 

    Kinase Assay: LY404039 is an inhibitor for mGluR1(Ki=149 nM) and mGluR2(Ki= 92 nM), which can also inhibit dopamine receptor.

    Cell Assay: LY404039 is a nanomolar potent agonist at recombinant human mGlu2 and mGlu3 receptors (K(i) = 149 and 92, respectively) and in rat neurons expressing native mGlu2/3 receptors (Ki = 88). LY404039 is highly selective for mGlu2/3 receptors, showing more than 100-fold selectivity for these receptors, versus ionotropic glutamate receptors, glutamate transporters, and other receptors targeted by known anxiolytic and antipsychotic medications.

    In VivoLY404039 demonstrates higher plasma exposure and better oral bioavailability. LY404039 may be valuable in the treatment of neuropsychiatric disorders, including anxiety and psychosis. In wild-type animals, LY404039 significantly reverses d-amphetamine(AMP)-induced increase in ambulations, distance traveled, and reduced time spent at rest. LY404039 reverses phencyclidine (PCP)-evoked behaviors at 10 mg/kg. The antipsychotic-like effects of LY404039 on PCP and AMP-evoked behavioral activation are absent in mGlu2 and mGlu2/3 but not in mGlu3 receptor-deficient mice. In contrast, clozapine and risperidone inhibit PCP-evoked behaviors in both wild-type and mGlu2/3 receptor-deficient mice. LY404039 reduces responding on the EtOH in the pavlovian spontaneous recovery (PSR) test and reduces the expression of an alcohol deprivation effect (ADE) during relapse, but does not affect EtOH responding under maintenance conditions. LY404039 inhibits the expression of alcohol seeking and relapse behavior without altering alcohol self-administration behavior. Moreover, LY404039 attenuates amphetamine- and phencyclidine-induced hyperlocomotion. LY404039 could inhibit conditioned avoidance responding and also reduces fear-potentiated startle in rats and marble burying in mice. Importantly, LY404039 does not produce sedative effects or motor impairment in the conditioned avoidance task. LY404039 also increases dopamine and serotonin release/turnover in the prefrontal cortex.
    Animal modelSeparate mGlu2 and mGlu3 receptor knockout mice are established 
    Formulation & DosageDissolved in 0.9% saline and the pH is adjusted to 6.0 with 1 M NaOH; 10 mg/kg; i.p. injection 
    ReferencesJ Pharmacol Exp Ther. 2007 Apr;321(1):308-17; J Pharmacol Exp Ther. 2008 Jul;326(1):209-17; Behav Brain Res. 2006 Aug 10;171(2):207-15. 

    These protocols are for reference only. InvivoChem does not independently validate these methods.


    Displacement of [3H]LY341495 binding to mGlu receptors by LY354740 or LY404039 in forebrain tissue from adult rats (200–500 μg) or RGT cells expressing the designated receptors. J Pharmacol Exp Ther. 2008 Jul;326(1):209-17. 


    Selective inhibition of forskolin-stimulated cAMP formation by LY354740 or LY404039 in cells expressing group II (mGlu2 and mGlu3), but not group III (mGlu4, -6, -7, and -8) receptors. J Pharmacol Exp Ther. 2008 Jul;326(1):209-17. 


    Effects of LY404039 on EPSPs evoked in striatal neurons in vitro. J Pharmacol Exp Ther. 2008 Jul;326(1):209-17. 


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