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pomaglumetad (LY404039) GluR agonist

Name: pomaglumetad (LY404039)
Brand: Selleck Chemicals
SKU: S6001
Rating: 5 (8 reviews)

Cat.No.S6001

Pomaglumetad (LY404039) is a potent agonist of recombinant human mGlu2/mGlu3 receptors with K_i of 149 nM/92 nM, and it shows >100-fold selectivity over ionotropic glutamate receptors, glutamate transporters, and other receptors. This compound has reached Phase 3.

Chemical Structure

Molecular Weight: 235.22

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Quality Control

Batch: Purity: 99.94%

99.94

Related Targets	Adrenergic Receptor AChR 5-HT Receptor COX Calcium Channel Histamine Receptor Dopamine Receptor GABA Receptor TRP Channel Cholinesterase (ChE)
Other GluR Inhibitors	(S)-Glutamic acid CTEP (RO4956371) L-Glutamic acid monosodium salt Xanthurenic Acid O-Phospho-L-serine Capric acid ADX-47273 VU 0357121 MPEP VU 0364439

Chemical Information, Storage & Stability

Molecular Weight	235.22	Formula	C₇H₉NO₆S	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	635318-11-5	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	C1C(C2C(C2S1(=O)=O)C(=O)O)(C(=O)O)N

Solubility

In vitro
Batch:

5%TFA : 3.06 mg/mL

DMSO : 0.5 mg/mL (2.12 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Clear solution	30%propylene glycol 1 5%Tween80 2 65%D5W Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	30.000mg/ml (127.54mM)	Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified propylene glycol stock solution to 50 μL of Tween 80, mix evenly to clarify it; then continue to add 650 μL of D5W to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Features	Under investigation as an exciting new medicine that may herald the arrival of third-generation antipsychotic drugs.
Targets/IC₅₀/Ki	Rat neurons expressing native mGlu2/3 88 nM(Ki) Recombinant human mGlu3 92 nM(Ki) Recombinant human mGlu2 149 nM(Ki)
In vitro	Pomaglumetad (LY404039) exhibits low binding affinity to group III mGlu receptors including mGlu6, mGlu7 and mGlu8 with a K_i value more than 5 μM, and shows little affinity for ionotropic glutamate receptors, glutamate transporter subtypes, monoamine and other receptors. It potently inhibits forskolin-stimulated cAMP formation in cells expressing human mGlu2 and mGlu3 receptors. This compound suppresses electrically evoked excitatory activity in the striatum, and serotonin-induced L-glutamate release in the prefrontal cortex. It 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.
In vivo	Pomaglumetad (LY404039) demonstrates higher plasma exposure and better oral bioavailability, and may be valuable in the treatment of neuropsychiatric disorders, including anxiety and psychosis. In wild-type animals, this compound significantly reverses d-amphetamine(AMP)-induced increase in ambulations, distance travelled, and reduced time spent at rest. It reverses phencyclidine (PCP)-evoked behaviours at 10 mg/kg. The antipsychotic-like effects of LY404039 on PCP and AMP-evoked behavioural activation are absent in mGlu2 and mGlu2/3 but not in mGlu3 receptor-deficient mice. In contrast, clozapine and risperidone inhibit PCP-evoked behaviours in both wild-type and mGlu2/3 receptor-deficient mice. It 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. This compound inhibits the expression of alcohol seeking and relapse behaviour without altering alcohol self-administration behaviour. Moreover, it attenuates amphetamine- and phencyclidine-induced hyperlocomotion. It could inhibit conditioned avoidance responding and also reduces fear-potentiated startle in rats and marble burying in mice. Importantly, it does not produce sedative effects or motor impairment in the conditioned avoidance task. It also increases dopamine and serotonin release/turnover in the prefrontal cortex.
References	[1] https://pubmed.ncbi.nlm.nih.gov/17204749/ [2] https://pubmed.ncbi.nlm.nih.gov/18424625/ [3] https://pubmed.ncbi.nlm.nih.gov/16678921/ [4] https://pubmed.ncbi.nlm.nih.gov/17384937/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT01659177	Withdrawn	Healthy Participants	Denovo Biopharma LLC	August 2012	Phase 1
NCT01637142	Completed	Healthy Participants	Denovo Biopharma LLC	July 2012	Phase 1
NCT01609218	Completed	Healthy Volunteer Study	Denovo Biopharma LLC	June 2012	Phase 1
NCT01475136	Completed	Hepatic Insufficiency	Denovo Biopharma LLC	November 2011	Phase 1

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