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pomaglumetad (LY404039) GluR agonist

Name: pomaglumetad (LY404039)
Brand: Selleck Chemicals
SKU: S6001
Rating: 5 (10 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.

pomaglumetad (LY404039) GluR agonist Chemical Structure

Estructura química

Peso molecular: 235.22

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Control de calidad (Quality Control)

Lote: Pureza: 99.94%

99.94

Dianas relacionadas	Adrenergic Receptor AChR 5-HT Receptor COX Calcium Channel Histamine Receptor Dopamine Receptor GABA Receptor TRP Channel Cholinesterase (ChE)
Otros GluR Inhibidores	O-Phospho-L-serine (S)-Glutamic acid ADX-47273 VU 0357121 MPEP CTEP (RO4956371) L-Glutamic acid monosodium salt Xanthurenic Acid CNQX Capric acid

Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular	235.22	Fórmula	C₇H₉NO₆S	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	635318-11-5	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	N/A			Smiles	C1C(C2C(C2S1(=O)=O)C(=O)O)(C(=O)O)N

Solubilidad (Solubility)

In vitro
Lote:

5%TFA : 3.06 mg/mL

DMSO : 0.5 mg/mL (2.12 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Water : Insoluble

Calculadora de Molaridad

Masa	Concentración	Volumen	Peso molecular
=	×	×

Calculadora de Dilución Calculadora de Peso Molecular

In vivo Lote:
Clear solution	30%propylene glycol 1 5%Tween80 2 65%D5W Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	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.

Calculadora de formulación in vivo (Solución clara)

Paso 1: Introduzca la información a continuación (Recomendado: Un animal adicional para tener en cuenta la pérdida durante el experimento)

Dosis: mg/kg Peso promedio de los animales: g Volumen de dosificación por animal:μL Número de animales:

Paso 2: Introduzca la formulación in vivo (Esto es solo la calculadora, no la formulación. Por favor, contáctenos primero si no hay una formulación in vivo en la sección de Solubilidad.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Resultados del cálculo:

Concentración de trabajo: mg/ml;

Método para preparar el líquido maestro de DMSO: mg fármaco predissuelto en μL DMSO ( Concentración del líquido maestro mg/mL, Por favor, contáctenos primero si la concentración excede la solubilidad del DMSO del lote del fármaco. )

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadirμL PEG300, mezclar y clarificar, luego añadirμL Tween 80, mezclar y clarificar, luego añadir μL ddH₂O, mezclar y clarificar.

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadir μL Aceite de maíz, mezclar y clarificar.

Nota: 1. Por favor, asegúrese de que el líquido esté claro antes de añadir el siguiente disolvente.
2. Asegúrese de añadir el (los) disolvente(s) en orden. Debe asegurarse de que la solución obtenida, en la adición anterior, sea una solución clara antes de proceder a añadir el siguiente disolvente. Se pueden utilizar métodos físicos como el vórtice, el ultrasonido o el baño de agua caliente para ayudar a la disolución.

Mecanismo de acción (Mechanism of Action)

Características	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 traveled, and reduced time spent at rest. It 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. 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 behavior without altering alcohol self-administration behavior. 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.
Referencias	[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/

Información del ensayo clínico (Clinical Trial Information)

(datos de https://clinicaltrials.gov, actualizado el 2024-05-22)

Número NCT	Reclutamiento	Condiciones	Patrocinador/Colaboradores	Fecha de inicio	Fases
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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