POMAGLUMETAD METHIONIL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C12H18N2O7S2.H2O
Molecular Weight	384.426
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.[H][C@@]12[C@@H](C(O)=O)[C@]1([H])S(=O)(=O)C[C@@]2(NC(=O)[C@@H](N)CCSC)C(O)=O

InChI

InChIKey=HQMAHCKDJKNYEK-LBMFEJOUSA-N

InChI=1S/C12H18N2O7S2.H2O/c1-22-3-2-5(13)9(15)14-12(11(18)19)4-23(20,21)8-6(7(8)12)10(16)17;/h5-8H,2-4,13H2,1H3,(H,14,15)(H,16,17)(H,18,19);1H2/t5-,6+,7+,8-,12-;/m0./s1

HIDE SMILES / InChI

Molecular Formula	C12H18N2O7S2
Molecular Weight	366.411
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24772351 | https://adisinsight.springer.com/drugs/800026989 | https://www.ncbi.nlm.nih.gov/pubmed/26861400https://www.ncbi.nlm.nih.gov/pubmed/17204749 | https://www.ncbi.nlm.nih.gov/pubmed/19588471 | https://www.ncbi.nlm.nih.gov/pubmed/18424625 | https://www.ncbi.nlm.nih.gov/pubmed/17384937 | https://www.ncbi.nlm.nih.gov/pubmed/20571979

LY404039 [(-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]-hexane-4,6-dicarboxylic acid] is an agonist of orthosteric metabotropic glutamate receptor (mGluR)2/3. In addition, it acts as an agonist at dopamine D2 receptors. LY404039 demonstrated broad antipsychotic and anxiolytic efficacy across multiple animal models. LY-2140023 is a methionine amide prodrug of LY-404039 being developed by Eli Lilly & Co for the potential oral treatment of schizophrenia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Metabotropic glutamate receptor 2 24 Target ID: CHEMBL5137 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17204749	Agonist 2678	149.0 nM [Ki]
Metabotropic glutamate receptor 3 16 Target ID: CHEMBL2888 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17204749	Agonist 2678	92.0 nM [Ki]
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19588471	Agonist 2678	80.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Schizophrenia 298 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20571979 https://www.ncbi.nlm.nih.gov/pubmed/17767166 http://adisinsight.springer.com/drugs/800026989	Primary		Phase III 656	Unknown Approved Use Unknown

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00ECUO	https://www.1pchem.com/search?query=1P00ECUO
A2B Chem	AG69040	http://a2bchem.com/prod/AG69040
AK Scientific	X6978	https://aksci.com/item_detail.php?cat=X6978
AK Scientific	X7608	https://aksci.com/item_detail.php?cat=X7608
ApexBio Technology	B1626	https://www.apexbt.com/catalogsearch/result/?q=B1626
BLD Pharm	BD167188	http://www.bldpharm.com/search/Search.html?keyword=BD167188
BOC Sciences	635318-11-5	http://www.bocsci.com/description.asp?cas=635318-11-5
Capot Chemical	28184	https://www.capotchem.com/search.do?q=28184
Cayman Chemical	18408	http://www.caymanchem.com/app/template/Product.vm/catalog/18408
Chem Scene	CS-1345	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1345
ChemShuttle	151952	https://www.chemshuttle.com/catalogsearch/result/?q=151952
Chemspace	CSC020617886	https://chem-space.com/CSC020617886
Chemspace	CSC030377800	https://chem-space.com/CSC030377800
Coresyn	CM11052	http://www.coresyn.com/search.do?q=CM11052
Enamine	BBV-107441529	http://www.enaminestore.com/catalog/BBV-107441529
Enamine	BBV-78308795	http://www.enaminestore.com/catalog/BBV-78308795
Excenen	EX-A2094	http://www.excenen.com/searchresultlist.php?id=EX-A2094
KeyOrganics	AS-19328	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-19328
Lab Network	LN01341947	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01341947
MedChem Express	HY-50906	https://www.medchemexpress.com/search.html?q=HY-50906&ft=&fa=&fp=
MolPort	MolPort-009-679-373	https://www.molport.com/shop/molecule-link/MolPort-009-679-373
Molnova	M15404	https://www.molnova.com/en/serch-list.html?keywords=M15404
MuseChem	I004395	https://www.musechem.com/product/I004395.html
Selleck Chemicals	S6001	http://www.selleckchem.com/search.html?searchDTO.searchParam=S6001
ShangHai Biochempartner	BCP000122	http://www.biochempartner.com/search_BCP000122
TargetMol	T6022	https://www.targetmol.com/search?keyword=T6022
eMolecules	32176431	https://orderbb.emolecules.com/search/#?query=32176431
eNovation Chemicals	D501762	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501762&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-7450652907	https://mcule.com/MCULE-7450652907/
mcule	MCULE-8272682120	https://mcule.com/MCULE-8272682120/

PubMed

Title	Date	PubMed
Synthesis and metabotropic glutamate receptor activity of S-oxidized variants of (-)-4-amino-2-thiabicyclo-[3.1.0]hexane-4,6-dicarboxylate: identification of potent, selective, and orally bioavailable agonists for mGlu2/3 receptors.	2007 Jan 25	17228865
Evidence for the role of metabotropic glutamate (mGlu)2 not mGlu3 receptors in the preclinical antipsychotic pharmacology of the mGlu2/3 receptor agonist (-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY404039).	2008 Jul	18424625
A Double-Blind, Placebo-Controlled Comparator Study of LY2140023 monohydrate in patients with schizophrenia.	2014 Dec 10	25539791
A short-term, multicenter, placebo-controlled, randomized withdrawal study of a metabotropic glutamate 2/3 receptor agonist using an electronic patient-reported outcome device in patients with schizophrenia.	2014 Oct	25006819
Exploratory analysis for a targeted patient population responsive to the metabotropic glutamate 2/3 receptor agonist pomaglumetad methionil in schizophrenia.	2015 Dec 1	25890643
Relative contributions of presystemic and systemic peptidases to oral exposure of a novel metabotropic glutamate 2/3 receptor agonist (LY404039) after oral administration of prodrug pomaglumetad methionil (LY2140023).	2015 Jan	25382826
Glutamate drug reduces dopamine inhibition of phosphorylation.	2016 Feb	26583745
Serotonin 2A Receptor SNP rs7330461 Association with Treatment Response to Pomaglumetad Methionil in Patients with Schizophrenia.	2016 Feb 5	26861400
In Vitro and Clinical Evaluations of the Drug-Drug Interaction Potential of a Metabotropic Glutamate 2/3 Receptor Agonist Prodrug with Intestinal Peptide Transporter 1.	2017 Feb	27895114
Group II metabotropic glutamate receptor agonist prodrugs LY2979165 and LY2140023 attenuate the functional imaging response to ketamine in healthy subjects.	2018 Jul	29564482
Successes, failures, and future prospects of prodrugs and their clinical impact.	2019 Mar	30714428

Patents

Sample Use Guides

In Vivo Use Guide

Phase 3 study for the treatment of schizophrenia: 40 mg LY2140023 (prodrug of LY404039) administered orally; given twice daily for up to 4 weeks. At the discretion of the investigator, dose may be adjusted one time to 80 mg. 80 mg dose may be adjusted back to 40 mg one time. Mice: 3-30 mg/kg i.p.

Route of Administration: Oral

In Vitro Use Guide

rat primary astrocytes were treated with 100 uM LY404039

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:55:15 GMT 2023` Edited by `admin` on `Fri Dec 15 15:55:15 GMT 2023`
Record UNII	WE665JB15R
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

POMAGLUMETAD METHIONIL

Official Name

English

LY-2140023 MONOHYDRATE

Code

English

POMAGLUMETAD METHIONIL [USAN]

Common Name

English

(1R,4S,5S,6S)-4-(L-METHIONYLAMINO)-2-THIABICYCLO(3.1.0)HEXANE-4,6-DICARBOXYLIC ACID 2,2-DIOXIDE MONOHYDRATE

Systematic Name

English

LY2140023 MONOHYDRATE

Code

English

4-(((2S)-2-AMINO-4-(METHYLTHIO)BUTANOYL)AMINO)-2-THIABICYCLO(3.1.0)HEXANE-4,6-DICARBOXYLIC ACID 2,2-DIOXIDE HYDRATE, 1R,4S,5S,6S

Common Name

English

Code System Code Type Description

EPA CompTox

DTXSID10241907