LY404039 - CAS 635318-11-5
Catalog number: B0084-146172
Category: Inhibitor
Please be kindly noted products are not for therapeutic use. We do not sell to patients.
Molecular Formula:
C7H9NO6S
Molecular Weight:
235.22
COA:
Inquire
Targets:
mGluR
Description:
LY-404,039, also known as pomaglumetad, is an amino acid analog drug that acts as a highly selective agonist for the metabotropic glutamate receptor group II subtypes mGluR2 and mGluR3.
Ordering Information
Catalog Number Size Price Stock Quantity
B0084-146172 50 mg $398 In stock
Bulk Inquiry
Purity:
>98%
Synonyms:
GW786034 HCl
MSDS:
Inquire
InChIKey:
AVDUGNCTZRCAHH-MDASVERJSA-N
InChI:
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
Canonical SMILES:
C1C(C2C(C2S1(=O)=O)C(=O)O)(C(=O)O)N
1.Role of calcium, glutamate and NMDA in major depression and therapeutic application.
Deutschenbaur L1, Beck J1, Kiyhankhadiv A1, Mühlhauser M1, Borgwardt S1, Walter M1, Hasler G1, Sollberger D1, Lang UE2. Prog Neuropsychopharmacol Biol Psychiatry. 2016 Jan 4;64:325-33. doi: 10.1016/j.pnpbp.2015.02.015. Epub 2015 Mar 4.
Major depression is a common, recurrent mental illness that affects millions of people worldwide. Recently, a unique fast neuroprotective and antidepressant treatment effect has been observed by ketamine, which acts via the glutamatergic system. Hence, a steady accumulation of evidence supporting a role for the excitatory amino acid neurotransmitter (EAA) glutamate in the treatment of depression has been observed in the last years. Emerging evidence indicates that N-methyl-D-aspartate (NMDA), group 1 metabotropic glutamate receptor antagonists and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) agonists have antidepressant properties. Indeed, treatment with NMDA receptor antagonists has shown the ability to sprout new synaptic connections and reverse stress-induced neuronal changes. Based on glutamatergic signaling, a number of therapeutic drugs might gain interest in the future. Several compounds such as ketamine, memantine, amantadine, tianeptine, pioglitazone, riluzole, lamotrigine, AZD6765, magnesium, zinc, guanosine, adenosine aniracetam, traxoprodil (CP-101,606), MK-0657, GLYX-13, NRX-1047, Ro25-6981, LY392098, LY341495, D-cycloserine, D-serine, dextromethorphan, sarcosine, scopolamine, pomaglumetad methionil, LY2140023, LY404039, MGS0039, MPEP, 1-aminocyclopropanecarboxylic acid, all of which target this system, have already been brought up, some of them recently.
2.Modulation of mGlu2 Receptors, but Not PDE10A Inhibition Normalizes Pharmacologically-Induced Deviance in Auditory Evoked Potentials and Oscillations in Conscious Rats.
Ahnaou A1, Biermans R1, Drinkenburg WH1. PLoS One. 2016 Jan 25;11(1):e0147365. doi: 10.1371/journal.pone.0147365. eCollection 2016.
Improvement of cognitive impairments represents a high medical need in the development of new antipsychotics. Aberrant EEG gamma oscillations and reductions in the P1/N1 complex peak amplitude of the auditory evoked potential (AEP) are neurophysiological biomarkers for schizophrenia that indicate disruption in sensory information processing. Inhibition of phosphodiesterase (i.e. PDE10A) and activation of metabotropic glutamate receptor (mGluR2) signaling are believed to provide antipsychotic efficacy in schizophrenia, but it is unclear whether this occurs with cognition-enhancing potential. The present study used the auditory paired click paradigm in passive awake Sprague Dawley rats to 1) model disruption of AEP waveforms and oscillations as observed in schizophrenia by peripheral administration of amphetamine and the N-methyl-D-aspartate (NMDA) antagonist phencyclidine (PCP); 2) confirm the potential of the antipsychotics risperidone and olanzapine to attenuate these disruptions; 3) evaluate the potential of mGluR2 agonist LY404039 and PDE10 inhibitor PQ-10 to improve AEP deficits in both the amphetamine and PCP models.
3.Hydrophilic interaction chromatography with aerosol-based detectors (ELSD, CAD, NQAD) for polar compounds lacking a UV chromophore in an intravenous formulation.
Cintrón JM1, Risley DS. J Pharm Biomed Anal. 2013 May 5;78-79:14-8. doi: 10.1016/j.jpba.2013.01.022. Epub 2013 Jan 26.
In this work, a high performance liquid chromatography (HPLC) method is reported for the separation and quantitation of a drug substance that is highly polar and lacking a chromophore in a mannitol intravenous (IV) formulation. Three polar stationary phases operated in hydrophilic interaction chromatography (HILIC) mode were evaluated in conjunction with an Alltech 800 ELSD detector. These columns were evaluated with respect to chromatographic properties such as buffer, pH and organic concentrations to identify the best stationary phase. The chromatographic method was then validated for the determination of mGlu2/3 receptor agonist (-)-(1R, 4S, 5S, 6S)-4-Amino-2-sulfonylbicyclo [3.1.0] hexane-4,6-dicarboxylic acid (LY404039) content in a mannitol IV formulation with respect to linearity (R(2) of 0.9997), repeatability (%RSD of 0.36%), accuracy, solution stability (99.56% after 24h), specificity, intra-assay precision (%RSD 0.48%) and limit of detection (LOD, ∼50 μg/mL).
4.In vitro characterization of the bioconversion of pomaglumetad methionil, a novel metabotropic glutamate 2/3 receptor agonist peptide prodrug.
Moulton RD1, Ruterbories KJ2, Bedwell DW2, Mohutsky MA2. Drug Metab Dispos. 2015 May;43(5):756-61. doi: 10.1124/dmd.114.062893. Epub 2015 Mar 9.
To characterize the hydrolysis of the peptide prodrug pomaglumetad methionil (LY2140023; (1R,4S,5S,6S)-4-(L-methionylamino)-2-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid 2,2-dioxide), to the active drug LY404039 [(1R,4S,5S,6S)-4-amino-2-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid 2,2-dioxide], a series of in vitro studies were performed in various matrices, including human intestinal, liver, kidney homogenate, and human plasma. The studies were performed to determine the tissue(s) and enzyme(s) responsible for the conversion of the prodrug to the active molecule. This could enable an assessment of the risk for drug interactions, an evaluation of pharmacogenomic implications, as well as the development of a Physiologically Based Pharmacokinetic (PBPK) model for formation of the active drug. Of the matrices examined, hydrolysis of pomaglumetad methionil was observed in intestinal and kidney homogenate preparations and plasma, but not in liver homogenate.
Molecular Weight Calculator Molarity Calculator Solution Dilution Calculator

Related mGluR Products


CAS 1315379-60-2 NPEC-caged-(1S,3R)-ACPD

NPEC-caged-(1S,3R)-ACPD
(CAS: 1315379-60-2)

A caged version of (1S,3R)-ACPD. (1S,3R)-ACPD is a group I/II mGlu agonist.

CAS 111900-32-4 (1S,3R)-ACPD

(1S,3R)-ACPD
(CAS: 111900-32-4)

(1S,3R)-ACPD, an isomer of (±)-trans-ACPD, has been found to be an agonist of mGluRs.

CAS 147782-19-2 DCG IV

DCG IV
(CAS: 147782-19-2)

DCG IV is a potent group II mGluR agonist and a presynaptic depressant.

CAS 890764-63-3 VU 1545

VU 1545
(CAS: 890764-63-3)

VU 1545 is a metabotropic glutamate receptor 5 (mGlu5) positive allosteric modulator (EC50 = 9.6 nM, Ki = 156 nM at rat mGlu5).

CAS 176199-48-7 LY 354740

LY 354740
(CAS: 176199-48-7)

LY 354740 is a selective group II mGlu receptors agonist with EC50 values are 5.1 and 24.3 nM at mGlu2 and mGlu3 receptors. It shows antianxiety and antiaddicti...

CAS 518357-51-2 3-MATIDA

3-MATIDA
(CAS: 518357-51-2)

3-MATIDA is a potent metabotropic glutamate (mGlu1) receptor antagonist with IC50 value of 6.3 μM at rat mGlu1a. It displays ≥ 40-fold selectivity over other re...

CAS 757950-09-7 Raseglurant

Raseglurant
(CAS: 757950-09-7)

Raseglurant is a negative allosteric modulator of the mGlu5 receptor and derivative of MPEP. It can be used for the treatment of migraine, gastroesophageal refl...

CAS 871362-31-1 CTEP

CTEP
(CAS: 871362-31-1)

CTEP is a novel, long-acting, orally bioavailable allosteric antagonist of mGlu5 receptor (IC50=2.2 nM), showing >1000-fold selectivity over other mGlu receptor...

CAS 1254977-87-1 JNJ-42153605

JNJ-42153605
(CAS: 1254977-87-1)

JNJ-42153605 is a selective positive allosteric modulator of the metabotropic glutamate 2 (mGlu2) receptor (EC50= 17 Nm) with an acceptable pharmacokinetic prof...

CAS 85148-82-9 (S)-4-Carboxy-3-hydroxyphenylglycine

(S)-4-Carboxy-3-hydroxyphenylglycine
(CAS: 85148-82-9)

(S)-4C3H-PG has been found to be a competitive GluR1 glutamate receptor antagonist as well as metabotropic GluR2/3 glutamate receptor agonist.

CAS 334887-43-3 HexylHIBO

HexylHIBO
(CAS: 334887-43-3)

HexylHIBO is a Group I mGlu receptor antagonist (Ki = 140 and 110 μM at mGlu1a and mGlu5a receptors, respectively). HexylHIBO was shown to decrease sEPSCs in ra...

CAS 693288-97-0 CPPHA

CPPHA
(CAS: 693288-97-0)

CPPHA is a selective positive allosteric modulator of mGluR5 receptor. It is thought to act at a novel allosteric site and potentiates mGlu5 responses by a mech...

CAS 169209-63-6 (2R,4R)-APDC

(2R,4R)-APDC
(CAS: 169209-63-6)

(2R,4R)-APDC is a selective and relatively potent group II mGluR agonist (EC50 = 0.4, 0.4, > 100, > 100, > 300 and > 300 μM for human mGlu2, mGlu3, mGlu1, mGlu5...

CAS 15332-10-2 DFB

DFB
(CAS: 15332-10-2)

DFB is a selective allosteric potentiator of the metabotropic glutamate receptor mGlu5. DFB exhibits no agonistic activity itself, but potentiates (3 - 6-fold) ...

CAS 1259372-69-4 VU 0155041 sodium salt

VU 0155041 sodium salt
(CAS: 1259372-69-4)

VU 0155041 sodium salt is a potent positive allosteric modulator at mGlu4 receptors (EC50 = 798 and 693 nM at human and rat mGlu4 receptors, respectively). VU 0...

CAS 1630936-95-6 VU 0422288

VU 0422288
(CAS: 1630936-95-6)

VU 0422288 is a group III mGlu receptor positive allosteric modulator (EC50 = 108, 125 and 146 nM for mGlu4, mGlu8 and mGlu7, respectively) with selectivity ove...

CAS 869802-58-4 A 841720

A 841720
(CAS: 869802-58-4)

A 841720 is a potent non-competitive mGlu1 receptor antagonist (IC50 = 10 nM) exhibiting 34-fold selectivity over mGluR5 and inactive to other mGluR receptors, ...

CAS 524924-76-3 Methoxy-PEPy

Methoxy-PEPy
(CAS: 524924-76-3)

Methoxy-PEPy is a potent and highly selective mGlu5 receptor antagonist.

CAS 195209-04-2 ACPT-II

ACPT-II
(CAS: 195209-04-2)

ACPT-II has been found to be a mGluR antagonist and could probably exhibit neuroprotective effects.

CAS 201943-63-7 LY341495

LY341495
(CAS: 201943-63-7)

Very selective nanomolar potent antagonist for group II mGlu receptors. Also a relatively potent antagonist for group III mGlu receptors at high nanomolar to lo...

Chemical Structure

CAS 635318-11-5 LY404039

Quick Inquiry

Verification code

Featured Items