EGLUMETAD

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C8H11NO4
Molecular Weight	185.1772
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC[C@@](N)(C(O)=O)[C@]1([H])[C@H]2C(O)=O

InChI

InChIKey=VTAARTQTOOYTES-RGDLXGNYSA-N

InChI=1S/C8H11NO4/c9-8(7(12)13)2-1-3-4(5(3)8)6(10)11/h3-5H,1-2,9H2,(H,10,11)(H,12,13)/t3-,4-,5-,8-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C8H11NO4
Molecular Weight	185.1772
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12789623https://www.ncbi.nlm.nih.gov/pubmed/16223873 | https://www.ncbi.nlm.nih.gov/pubmed/15821951
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800008428 https://en.wikipedia.org/wiki/Eglumegad https://www.ncbi.nlm.nih.gov/pubmed/17712352 https://www.ncbi.nlm.nih.gov/pubmed/17204749

Talaglumetad (also known as LY-544344) is a bicyclohexane derivative patented by Eli Lilly and Company as modulators of metabotropic glutamate receptor. Talaglumetad acts as a prodrug of Eglumegad, a selective agonist of metabotropic glutamate receptors (mGluR2/3) and metabolized to release active compound by both human jejunal homogenates and rat liver homogenates. In experiments on mice, Talaglumetad was found to be as effective as diazepam for treating anxiety symptoms in several standard tests, but without producing any of the negative side effects of diazepam such as sedation and memory impairment.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Metabotropic glutamate receptor 2 24 Target ID: CHEMBL5137 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21334855 \| https://www.ncbi.nlm.nih.gov/pubmed/9144636	Agonist 2678		99.0 nM [Ki]
Metabotropic glutamate receptor 3 16 Target ID: CHEMBL2888 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21334855 \| https://www.ncbi.nlm.nih.gov/pubmed/9144636	Agonist 2678		94.0 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Generalized anxiety disorder 32 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17712352 https://www.ncbi.nlm.nih.gov/pubmed/12789623 https://www.ncbi.nlm.nih.gov/pubmed/13129812	Primary	Phase II 1132	Unknown Approved Use Unknown
Schizophrenia 298 Sources: http://adisinsight.springer.com/drugs/800008428 https://www.ncbi.nlm.nih.gov/pubmed/19179851	Primary	Preclinical	Unknown Approved Use Unknown
Smoking withdrawal 4 Sources: http://adisinsight.springer.com/drugs/800008428 https://www.ncbi.nlm.nih.gov/pubmed/9517421	Primary	Preclinical	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
200 mg 1 times / day multiple, oral (unknown) Studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16192835	unhealthy n = 18 Health Status: unhealthy Condition: panic disorder Sex: M+F Food Status: UNKNOWN Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/16192835	Disc. AE: headache, Nausea... AEs leading to discontinuation/dose reduction: headache (1 pt) Nausea (1 pt) allergic reaction (2 patients) Dizziness (1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/16192835

AEs

AE	Significance	Dose	Population
Dizziness	1 pt Disc. AE	200 mg 1 times / day multiple, oral (unknown) Studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16192835	unhealthy n = 18 Health Status: unhealthy Condition: panic disorder Sex: M+F Food Status: UNKNOWN Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/16192835
Nausea	1 pt Disc. AE	200 mg 1 times / day multiple, oral (unknown) Studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16192835	unhealthy n = 18 Health Status: unhealthy Condition: panic disorder Sex: M+F Food Status: UNKNOWN Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/16192835
headache	1 pt Disc. AE	200 mg 1 times / day multiple, oral (unknown) Studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16192835	unhealthy n = 18 Health Status: unhealthy Condition: panic disorder Sex: M+F Food Status: UNKNOWN Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/16192835
allergic reaction	2 patients Disc. AE	200 mg 1 times / day multiple, oral (unknown) Studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16192835	unhealthy n = 18 Health Status: unhealthy Condition: panic disorder Sex: M+F Food Status: UNKNOWN Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/16192835

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363681314	no

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P0024X8	https://www.1pchem.com/search?query=1P0024X8
ApexBio Technology	B7328	https://www.apexbt.com/catalogsearch/result/?q=B7328
BLD Pharm	BD630456	http://www.bldpharm.com/search/Search.html?keyword=BD630456
BOC Sciences	118457-14-0	http://www.bocsci.com/description.asp?cas=118457-14-0
BOC Sciences	176199-48-7	http://www.bocsci.com/description.asp?cas=176199-48-7
Capot Chemical	18158	https://www.capotchem.com/search.do?q=18158
Chem Scene	CS-5052	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-5052
Chemspace	CSC015520788	https://chem-space.com/CSC015520788
Chemspace	CSC015596037	https://chem-space.com/CSC015596037
Chemspace	CSC015819205	https://chem-space.com/CSC015819205
Chemspace	CSC037827371	https://chem-space.com/CSC037827371
Chemspace	CSC055343638	https://chem-space.com/CSC055343638
Debye Scientific	DB-028800	https://www.debyesci.com/index.php?id=product&ext[cno]=DB-028800
Enamine	BBV-107321178	http://www.enaminestore.com/catalog/BBV-107321178
Enamine	BBV-77536105	http://www.enaminestore.com/catalog/BBV-77536105
Enamine	BBV-77594264	http://www.enaminestore.com/catalog/BBV-77594264
Enamine	BBV-77710497	http://www.enaminestore.com/catalog/BBV-77710497
Enamine	BBV-93151106	http://www.enaminestore.com/catalog/BBV-93151106
MedChem Express	HY-18941	https://www.medchemexpress.com/search.html?q=HY-18941&ft=&fa=&fp=
MolPort	MolPort-004-797-150	https://www.molport.com/shop/molecule-link/MolPort-004-797-150
MolPort	MolPort-023-276-716	https://www.molport.com/shop/molecule-link/MolPort-023-276-716
Molnova	M12658	https://www.molnova.com/en/serch-list.html?keywords=M12658
Tocris	3246	https://www.tocris.com/search.php?Type=QuickSearch&Value=3246
Toronto Research Chemicals	L503128	https://www.trc-canada.com/product-detail/?CatNum=L503128
Wonderchem	WD05L2P	http://www.wonder-chem.com/search.html?text=WD05L2P
eMolecules	31420520	https://orderbb.emolecules.com/search/#?query=31420520
eMolecules	36500492	https://orderbb.emolecules.com/search/#?query=36500492
eMolecules	48882962	https://orderbb.emolecules.com/search/#?query=48882962
mcule	MCULE-4405877923	https://mcule.com/MCULE-4405877923/

PubMed

Title	Date	PubMed
A novel orally active group 2 metabotropic glutamate receptor agonist: LY354740.	1997 Apr 14	9172154
LY354740 is a potent and highly selective group II metabotropic glutamate receptor agonist in cells expressing human glutamate receptors.	1997 Jan	9144636
Characterization of [3H]-(2S,2'R,3'R)-2-(2',3'-dicarboxy-cyclopropyl)glycine ([3H]-DCG IV) binding to metabotropic mGlu2 receptor-transfected cell membranes.	1998 Feb	9504391
LY354740, a group II metabotropic glutamate receptor agonist with potential antiparkinsonian properties in rats.	1998 Oct	9826074
Cloning and functional expression of alternative spliced variants of the human metabotropic glutamate receptor 8.	1999 Apr 20	10216218
Potential anti-anxiety, anti-addictive effects of LY 354740, a selective group II glutamate metabotropic receptors agonist in animal models.	1999 Dec	10608278
Synthesis, pharmacological characterization, and molecular modeling of heterobicyclic amino acids related to (+)-2-aminobicyclo[3.1.0] hexane-2,6-dicarboxylic acid (LY354740): identification of two new potent, selective, and systemically active agonists for group II metabotropic glutamate receptors.	1999 Mar 25	10090786
[3H]-LY341495 as a novel antagonist radioligand for group II metabotropic glutamate (mGlu) receptors: characterization of binding to membranes of mGlu receptor subtype expressing cells.	1999 Oct	10530814
The role of metabotropic glutamate receptor (mGluR) ligands in parkinsonian muscle rigidity.	2000	11026478
Characterization of [(3)H]-LY354740 binding to rat mGlu2 and mGlu3 receptors expressed in CHO cells using semliki forest virus vectors.	2000 Jul 24	10884552
The antianxiety-like effects of antagonists of group I and agonists of group II and III metabotropic glutamate receptors after intrahippocampal administration.	2001 Oct	11685389
The role of striatal metabotropic glutamate receptors in Parkinson's disease.	2002	12373537
Modulation of DOI-induced increases in cortical BDNF expression by group II mGlu receptors.	2002 Sep	12117585
LY-354740 (Eli Lilly).	2003 Jan	12789623
Gateways to clinical trials.	2005 Jun	16082422
5-Hydroxytryptamine2A (5-HT2A) receptor regulation in rat prefrontal cortex: interaction of a phenethylamine hallucinogen and the metabotropic glutamate2/3 receptor agonist LY354740.	2006 Aug 7	16759803
The mGlu2/3 receptor agonist LY354740 suppresses immobilization stress-induced increase in rat prefrontal cortical BDNF mRNA expression.	2006 May 8	16469447
Pharmacological and pharmacokinetic properties of a structurally novel, potent, and selective metabotropic glutamate 2/3 receptor agonist: in vitro characterization of agonist (-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]-hexane-4,6-dicarboxylic acid (LY404039).	2007 Apr	17204749
Efficacy and tolerability of an mGlu2/3 agonist in the treatment of generalized anxiety disorder.	2008 Jun	17712352
Transepithelial transport of the group II metabotropic glutamate 2/3 receptor agonist (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate (LY354740) and its prodrug (1S,2S,5R,6S)-2-[(2'S)-(2'-amino)propionyl]aminobicyclo[3.1.0]hexane-2,6-dicarboxylate (LY544344).	2009 Jan	18838508

Patents

Sample Use Guides

In Vivo Use Guide

100 or 200 mg (LY354740)

Route of Administration: Oral

In Vitro Use Guide

LY354740 failed to inhibit Dopamine D(2) receptor binding in both native striatal tissue homogenates and cloned receptors at concentrations up to 10 uM.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 16:20:05 GMT 2023` Edited by `admin` on `Sat Dec 16 16:20:05 GMT 2023`
Record UNII	ONU5A67T2S
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

EGLUMETAD

Official Name

English

EGLUMETAD [USAN]

Common Name

English

EGLUMETAD ANHYDROUS

Common Name

English

(+)-(1S,2S,5R,6S)-2-AMINOBICYCLO(3.1.0)HEXANE-2,6-DICARBOXYLIC ACID

Systematic Name

English

EGLUMEGAD

Common Name

English

eglumetad [INN]

Common Name

English

BICYCLO(3.1.0)HEXANE-2,6-DICARBOXYLIC ACID, 2-AMINO-, (1S,2S,5R,6S)-

Common Name

English

LY-354740

Code

English

LY354740

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C28197