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Details

Stereochemistry ABSOLUTE
Molecular Formula C12H18N2O7S2
Molecular Weight 366.411
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of POMAGLUMETAD METHIONIL ANHYDROUS

SMILES

[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=VOYCNOJFAJAILW-CAMHOICYSA-N
InChI=1S/C12H18N2O7S2/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)/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 4 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

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

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Agonist
2678
 149.0 nM [Ki]
Agonist
2678
 92.0 nM [Ki]
Agonist
2678
 80.0 nM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase III
656
Unknown

Approved Use

Unknown
Sourcing

Sourcing

Vendor/AggregatorIDURL
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

PubMed

TitleDatePubMed
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
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
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
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
Glutamate modulators as potential therapeutic drugs in schizophrenia and affective disorders.
2013 Aug
An agonist at glutamate and dopamine D2 receptors, LY404039.
2013 Mar
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
Pomaglumetad methionil: no significant difference as an adjunctive treatment for patients with prominent negative symptoms of schizophrenia compared to placebo.
2013 Nov
A Double-Blind, Placebo-Controlled Comparator Study of LY2140023 monohydrate in patients with schizophrenia.
2014 Dec 10
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
Serotonin 2A Receptor SNP rs7330461 Association with Treatment Response to Pomaglumetad Methionil in Patients with Schizophrenia.
2016 Feb 5
Group II metabotropic glutamate receptor agonist prodrugs LY2979165 and LY2140023 attenuate the functional imaging response to ketamine in healthy subjects.
2018 Jul
Successes, failures, and future prospects of prodrugs and their clinical impact.
2019 Mar
Patents

Patents

20050222231
3
20080182889
3
20100113579
3
20110207672
3
20110237602
6
US20160367554
3
US8735397
3
WO2003084610A1
3

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 19:15:37 GMT 2023
Edited
by admin
on Fri Dec 15 19:15:37 GMT 2023
Record UNII
3V85EZ3KFQ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
POMAGLUMETAD METHIONIL ANHYDROUS
Common Name English
LY-2140023
Code English
(1R,4S,5S,6S)-4-(L-METHIONYLAMINO)-2-THIABICYCLO(3.1.0)HEXANE-4,6-DICARBOXYLIC ACID 2,2-DIOXIDE
Systematic Name English
Pomaglumetad methionil [WHO-DD]
Common Name English
pomaglumetad methionil [INN]
Common Name English
LY2140023
Code English
2-THIABICYCLO(3.1.0)HEXANE-4,6-DICARBOXYLIC ACID, 4-(((2S)-2-AMINO-4-(METHYLTHIO)-1-OXOBUTYL)AMINO)-, 2,2-DIOXIDE, (1R,4S,5S,6S)-
Common Name English
Code System Code Type Description
PUBCHEM
25195354
Created by admin on Fri Dec 15 19:15:37 GMT 2023 , Edited by admin on Fri Dec 15 19:15:37 GMT 2023
PRIMARY
EVMPD
SUB33228
Created by admin on Fri Dec 15 19:15:37 GMT 2023 , Edited by admin on Fri Dec 15 19:15:37 GMT 2023
PRIMARY
DRUG BANK
DB05096
Created by admin on Fri Dec 15 19:15:37 GMT 2023 , Edited by admin on Fri Dec 15 19:15:37 GMT 2023
PRIMARY
NCI_THESAURUS
C166703
Created by admin on Fri Dec 15 19:15:37 GMT 2023 , Edited by admin on Fri Dec 15 19:15:37 GMT 2023
PRIMARY
INN
9404
Created by admin on Fri Dec 15 19:15:37 GMT 2023 , Edited by admin on Fri Dec 15 19:15:37 GMT 2023
PRIMARY
CAS
635318-55-7
Created by admin on Fri Dec 15 19:15:37 GMT 2023 , Edited by admin on Fri Dec 15 19:15:37 GMT 2023
PRIMARY
FDA UNII
3V85EZ3KFQ
Created by admin on Fri Dec 15 19:15:37 GMT 2023 , Edited by admin on Fri Dec 15 19:15:37 GMT 2023
PRIMARY
EPA CompTox
DTXSID00212944
Created by admin on Fri Dec 15 19:15:37 GMT 2023 , Edited by admin on Fri Dec 15 19:15:37 GMT 2023
PRIMARY
Related Record Type Details
Structure of POMAGLUMETAD METHIONIL
SOLVATE->ANHYDROUS
Structure of POMAGLUMETAD METHIONIL
SALT/SOLVATE -> PARENT
Related Record Type Details
Structure of POMAGLUMETAD
METABOLITE ACTIVE -> PRODRUG
Related Record Type Details
Structure of POMAGLUMETAD
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