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

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
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
Comment on: "Adverse events in healthy subjects exposed to single and multiple doses of LY2140023 monohydrate" by Ayan-Oshodi et al (J Clin Psychopharmacol 2012;32[3]:408-411).	2013 Apr	23422392
Glutamate modulators as potential therapeutic drugs in schizophrenia and affective disorders.	2013 Aug	23455590
A long-term, phase 2, multicenter, randomized, open-label, comparative safety study of pomaglumetad methionil (LY2140023 monohydrate) versus atypical antipsychotic standard of care in patients with schizophrenia.	2013 May 22	23694720
Pomaglumetad methionil: no significant difference as an adjunctive treatment for patients with prominent negative symptoms of schizophrenia compared to placebo.	2013 Nov	24035403
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
The quality of reporting of phase II and III trials for new antipsychotics: a systematic review.	2015 Feb	25065545
Approaches to intravenous clinical pharmacokinetics: Recent developments with isotopic microtracers.	2016 Jan	26073308
Role of calcium, glutamate and NMDA in major depression and therapeutic application.	2016 Jan 4	25747801
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

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