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| 10mg |
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| 25mg |
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| 50mg |
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| 250mg |
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Purity: ≥98%
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.
| ln Vitro |
In rats with neurons expressing native mGlu2/3 receptors (Ki=88 nM), LY404039 is a nanomolar potent agonist [1]. Functioning as a potent inhibitor of forskolin-stimulated cAMP formation, LY404039 acts on cells that express human mGlu2 (EC50=23 nM) and mGlu3 (EC50=48 nM) receptors [1]. According to electrophysiological research, LY404039 suppresses serotonin-induced L-glutamate release in the prefrontal cortex and electrically evoked excitatory activity in the striatum. LY404039 exhibits a maximum inhibition of 85.6% at 1 μM, effectively suppressing the frequency of 5-HT-induced excitatory postsynaptic currents (EPSC) with an EC50 of 82.3 nM [1]. LY404039 blocks the human cloned D2 receptor from binding to the D2-specific antagonist [3H]domperidone, with a dissociation constant of 8.2 nM for high D2 and 1640 nM for low D2. The dissociation constants of LY404039 were determined using rat striatal tissue, and they were 12.6 nM at D2 high and 2100 nM at D2 low [2].
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| ln Vivo |
LY404039 reduces hyperkinesis brought on by amphetamines (3–30 mg/kg) and phencyclidines (10 mg/kg), respectively. The conditioned avoidance responses are inhibited by LY404039 (3–10 mg/kg). Additionally, marble burying in mice (3–10 mg/kg) and fear-potentiated startle in rats (3–30 μg/kg) are both decreased by LY404039, indicating anxiolytic-like effects. Additionally, LY404039 (10 mg/kg) enhances serotonin and dopamine release/turnover in the prefrontal cortex [3]. Exposure increased proportionately with the dose after LY404039 was given orally to fasting rats at doses of 1, 3, or 10 mg/kg. In rats treated with LY404039 (10 mg/kg; po), the Cmax was 1528.5 ng/mL and the Tmax was 2 hours [1].
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| References |
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| Additional Infomation |
LY404039 is an organic heterobicyclic compound that is (1S,5R)-2-thiabicyclo[3.1.0]hexane carrying oxo, oxo, amino, carboxy, and carboxy groups at positions 2, 2, 4S, 4S, and 6S, respectively. It is a potent agonist of group II metabotropic glutamate receptors mGluR2 mGluR3 (Ki = 149 nM and 92 nM, respectively) and exhibits antipsychotic and anxiolytic efficacy in animal models. It has a role as a metabotropic glutamate receptor agonist, an antipsychotic agent, an anxiolytic drug and a dopamine agonist. It is a dicarboxylic acid, a bridged compound, an organic heterobicyclic compound, a sulfone and a non-proteinogenic amino acid derivative.
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| Molecular Formula |
C7H9NO6S
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| Molecular Weight |
235.22
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| Exact Mass |
235.015
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| CAS # |
635318-11-5
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| Related CAS # |
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| PubChem CID |
9834591
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| Appearance |
White to gray solid powder
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| Density |
1.9±0.1 g/cm3
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| Boiling Point |
600.3±55.0 °C at 760 mmHg
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| Flash Point |
316.8±31.5 °C
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| Vapour Pressure |
0.0±3.7 mmHg at 25°C
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| Index of Refraction |
1.661
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| LogP |
-2.02
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
15
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| Complexity |
451
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C1[C@]([C@@H]2[C@H]([C@@H]2S1(=O)=O)C(=O)O)(C(=O)O)N
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| InChi Key |
AVDUGNCTZRCAHH-MDASVERJSA-N
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| InChi Code |
InChI=1S/C7H9NO6S/c8-7(6(11)12)1-15(13,14)4-2(3(4)7)5(9)10/h2-4H,1,8H2,(H,9,10)(H,11,12)/t2-,3-,4+,7+/m1/s1
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| Chemical Name |
(1R,4S,5S,6S)-4-amino-2,2-dioxo-2λ6-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2 mg/mL (8.50 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).
Solubility in Formulation 2: 30% propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.2513 mL | 21.2567 mL | 42.5134 mL | |
| 5 mM | 0.8503 mL | 4.2513 mL | 8.5027 mL | |
| 10 mM | 0.4251 mL | 2.1257 mL | 4.2513 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03106571 | Terminated | Drug: Pomaglumetad methionil Drug: Placebo Drug: Methamphetamine |
Methamphetamine Use Disorder | University of California, Los Angeles | August 1, 2017 | Phase 1 |
| NCT01487083 | Terminated | Drug: Pomaglumetad methionil | Schizophrenia | Eli Lilly and Company | December 2011 | Phase 3 |
| NCT02919774 | Completed | Drug: POMA Drug: placebo |
Healthy Controls | New York State Psychiatric Institute | October 2016 | Phase 1 |
| NCT02234687 | Terminated Has Results | Drug: Pomaglumetad Methionil 160mg Drug: Pomaglumetad Methionil 40mg Drug: Placebo |
Post-traumatic Stress Disorder | NYU Langone Health | September 2014 | Phase 1 |
| NCT01606436 | Completed Has Results | Drug: LY2140023 Drug: Placebo Drug: Moxifloxacin |
Schizophrenic Disorders | Denovo Biopharma LLC | June 2012 | Phase 1 |
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