CAS 635318-11-5|LY404039

Introduction：Basic information about CAS 635318-11-5|LY404039, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. LY404039 BiologicalActivity
3. Chemical & Physical Properties
4. Synonyms

Common Name	LY404039
CAS Number	635318-11-5	Molecular Weight	235.214
Density	1.9±0.1 g/cm3	Boiling Point	600.3±55.0 °C at 760 mmHg
Molecular Formula	C₇H₉NO₆S	Melting Point	/
MSDS	/	Flash Point	316.8±31.5 °C

Names

Name	(1R,4S,5S,6S)-4-amino-2,2-dioxo-2λ6-thia-bicyclo[3.1.0]hexane-4,6-dicarboxylic acid
Synonym	More Synonyms

LY404039 BiologicalActivity

Description	LY404039 is an inhibitor for mGluR1(Ki=149 nM) and mGluR2(Ki= 92 nM), which can also inhibit dopamine receptor.IC50 Value:149 nM(Ki for mGlu2); 92 nM(Ki for mGlu3)[1]Target: mGluR1; mGluR2Metabotropic glutamate (mGlu) receptors have been shown to mediate a number of behaviors including emotionality and responsivity to stress as demonstrated by efficacy in preclinical and clinical studies.in vitro: Similar to LY354740, 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[1].in vivo: LY404039 attenuated amphetamine- and phencyclidine-induced hyperlocomotion (3-30 and 10 mg/kg, respectively). LY404039 (3-10 mg/kg) inhibited conditioned avoidance responding. LY404039 also reduced fear-potentiated startle in rats (3-30 microg/kg) and marble burying in mice (3-10 mg/kg), indicating anxiolytic-like effects. Importantly, LY404039 did not produce sedative effects or motor impairment as measured by rotarod performance and lack of escape failures in the conditioned avoidance task (at doses up to 30 and 10 mg/kg, respectively). LY404039 (10 mg/kg) also increased dopamine and serotonin release/turnover in the prefrontal cortex [3].Clinical trial: An Absolute Bioavailability Study of LY-2140023 and LY-404039 in Healthy Subjects Using the Intravenous Tracer Method. Phage1
Related Catalog	Signaling Pathways >>GPCR/G Protein >>mGluRResearch Areas >>Neurological Disease
References	[1]. Rorick-Kehn LM, Johnson BG, Burkey JL, Pharmacological and pharmacokinetic properties of a structurally novel, potent, and selective metabotropic glutamate 2/3 receptor agonist: in vitro characterizationofagonist(-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]-hexane-4,6-dicarboxylic acid (LY404039). J Pharmacol Exp Ther. 2007 Apr;321(1):308-17. [2]. Seeman P. An agonist at glutamate and dopamine D2 receptors, LY404039. Neuropharmacology. 2013 Mar;66:87-8. [3]. Rorick-Kehn LM, Johnson BG, Knitowski KM, In vivo pharmacological characterization of the structurally novel, potent, selective mGlu2/3 receptor agonistLY404039 in animal models of psychiatric disorders. Psychopharmacology (Berl). 2007 Jul;193(1):121-36.

Description

LY404039 is an inhibitor for mGluR1(Ki=149 nM) and mGluR2(Ki= 92 nM), which can also inhibit dopamine receptor.IC50 Value:149 nM(Ki for mGlu2); 92 nM(Ki for mGlu3)[1]Target: mGluR1; mGluR2Metabotropic glutamate (mGlu) receptors have been shown to mediate a number of behaviors including emotionality and responsivity to stress as demonstrated by efficacy in preclinical and clinical studies.in vitro: Similar to LY354740, 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[1].in vivo: LY404039 attenuated amphetamine- and phencyclidine-induced hyperlocomotion (3-30 and 10 mg/kg, respectively). LY404039 (3-10 mg/kg) inhibited conditioned avoidance responding. LY404039 also reduced fear-potentiated startle in rats (3-30 microg/kg) and marble burying in mice (3-10 mg/kg), indicating anxiolytic-like effects. Importantly, LY404039 did not produce sedative effects or motor impairment as measured by rotarod performance and lack of escape failures in the conditioned avoidance task (at doses up to 30 and 10 mg/kg, respectively). LY404039 (10 mg/kg) also increased dopamine and serotonin release/turnover in the prefrontal cortex [3].Clinical trial: An Absolute Bioavailability Study of LY-2140023 and LY-404039 in Healthy Subjects Using the Intravenous Tracer Method. Phage1

Related Catalog

Signaling Pathways >>GPCR/G Protein >>mGluRResearch Areas >>Neurological Disease

References

[1]. Rorick-Kehn LM, Johnson BG, Burkey JL, Pharmacological and pharmacokinetic properties of a structurally novel, potent, and selective metabotropic glutamate 2/3 receptor agonist: in vitro characterizationofagonist(-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]-hexane-4,6-dicarboxylic acid (LY404039). J Pharmacol Exp Ther. 2007 Apr;321(1):308-17.

[2]. Seeman P. An agonist at glutamate and dopamine D2 receptors, LY404039. Neuropharmacology. 2013 Mar;66:87-8.

[3]. Rorick-Kehn LM, Johnson BG, Knitowski KM, In vivo pharmacological characterization of the structurally novel, potent, selective mGlu2/3 receptor agonistLY404039 in animal models of psychiatric disorders. Psychopharmacology (Berl). 2007 Jul;193(1):121-36.

Chemical & Physical Properties

Density	1.9±0.1 g/cm3
Boiling Point	600.3±55.0 °C at 760 mmHg
Molecular Formula	C₇H₉NO₆S
Molecular Weight	235.214
Flash Point	316.8±31.5 °C
Exact Mass	235.015060
PSA	143.14000
LogP	-2.02
Vapour Pressure	0.0±3.7 mmHg at 25°C
Index of Refraction	1.661
InChIKey	AVDUGNCTZRCAHH-MDASVERJSA-N
SMILES	NC1(C(=O)O)CS(=O)(=O)C2C(C(=O)O)C21
Storage condition	-20℃

Synonyms

2-Thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid, 4-amino-, 2,2-dioxide, (1R,4S,5S,6S)-

LY-404,039

(1R,4S,5S,6S)-4-Amino-2-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid 2,2-dioxide

LY404039

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