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Technical Data
| Formula | C7H9NO6S |
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| Molecular Weight | 235.22 | CAS No. | 635318-11-5 | |
| Solubility (25°C)* | In vitro | DMSO | 1 mg/mL (4.25 mM) | |
| Water | Insoluble | |||
| Ethanol | Insoluble | |||
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
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Preparing Stock Solutions
Biological Activity
| Description | LY404039 is a potent agonist of recombinant human mGlu2/mGlu3 receptors with Ki of 149 nM/92 nM, shows >100-fold selectivity over ionotropic glutamate receptors, glutamate transporters, and other receptors. Phase 3. | ||||||
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| Targets |
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| In vitro | 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. [1] | ||||||
| In vivo | LY404039 demonstrates higher plasma exposure and better oral bioavailability. LY404039 may be valuable in the treatment of neuropsychiatric disorders, including anxiety and psychosis. [1] 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. [2] 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. [3] 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. [4] | ||||||
| Features | Under investigation as an exciting new medicine that may herald the arrival of third-generation antipsychotic drugs. |
Protocol (from reference)
| Animal Study:[2] |
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References
Customer Product Validation
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Data from [PLoS One, 2011, 6, e22235]
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, , Dr. Philip Seeman, Department of Pharmacology, University of Toronto
Selleck's pomaglumetad (LY404039) has been cited by 9 publications
| Peripubertal mGluR2/3 Agonist Treatment Prevents Hippocampal Dysfunction and Dopamine System Hyperactivity in Adulthood in MAM Model of Schizophrenia [ Schizophr Bull, 2021, sbab047] | PubMed: 33928393 |
| The mGluR2/3 agonist pomaglumetad methionil normalizes aberrant dopamine neuron activity via action in the ventral hippocampus [ Neuropsychopharmacology, 2020, 10.1038/s41386-020-0764-2] | PubMed: 32663839 |
| Fully automated head-twitch detection system for the study of 5-HT2A receptor pharmacology in vivo. [ Sci Rep, 2019, 9(1):14247] | PubMed: 31582824 |
| Allosteric signaling through an mGlu2 and 5-HT2A heteromeric receptor complex and its potential contribution to schizophrenia. [ Sci Signal, 2016, 9(410):ra5] | PubMed: 26758213 |
| Allosteric signaling through an mGlu2 and 5-HT2A heteromeric receptor complex and its potential contribution to schizophrenia [ Sci Signal, 2016, 9(410):ra5] | PubMed: 26758213 |
| Glutamate Drug Reduces Dopamine Inhibition of Phosphorylation [Su P, et al. Synapse, 2015, 70:45–48] | PubMed: 26583745 |
| Heterocomplex formation of 5-HT2A-mGlu2 and its relevance for cellular signaling cascades. [Delille HK, et al. Neuropharm, 2012, 62(7):2184-91] | PubMed: 22300836 |
| Reduced cAMP, Akt activation and p65-c-Rel dimerization: mechanisms involved in the protective effects of mGluR3 agonists in cultured astrocytes. [Durand D, et al. PLoS One, 2011, 6(7):e22235] | PubMed: 21779400 |
| Glutamate agonist LY404,039 for treating schizophrenia has affinity for the dopamine D2High receptor. [Seeman P, et al. Synapse, 2009, 63(10):935-9] | PubMed: 19588471 |
RETURN POLICY
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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.
NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.