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
SMILES
CSCC[C@H](N)C(=O)N[C@]1(CS(=O)(=O)[C@H]2[C@@H]([C@@H]12)C(O)=O)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
| 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 |
DescriptionSources: 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
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.
Originator
Sources: https://adisinsight.springer.com/drugs/800026989https://www.ncbi.nlm.nih.gov/pubmed/17204749 | https://www.ncbi.nlm.nih.gov/pubmed/17228865
Curator's Comment: # Eli Lilly
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Successes, failures, and future prospects of prodrugs and their clinical impact. | 2019-03 |
|
| Group II metabotropic glutamate receptor agonist prodrugs LY2979165 and LY2140023 attenuate the functional imaging response to ketamine in healthy subjects. | 2018-07 |
|
| 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. | 2017-02 |
|
| Serotonin 2A Receptor SNP rs7330461 Association with Treatment Response to Pomaglumetad Methionil in Patients with Schizophrenia. | 2016-02-05 |
|
| Glutamate drug reduces dopamine inhibition of phosphorylation. | 2016-02 |
|
| Role of calcium, glutamate and NMDA in major depression and therapeutic application. | 2016-01-04 |
|
| Approaches to intravenous clinical pharmacokinetics: Recent developments with isotopic microtracers. | 2016-01 |
|
| Exploratory analysis for a targeted patient population responsive to the metabotropic glutamate 2/3 receptor agonist pomaglumetad methionil in schizophrenia. | 2015-12-01 |
|
| Effect of pomaglumetad methionil on the QT interval in subjects with schizophrenia. | 2015-06 |
|
| In vitro characterization of the bioconversion of pomaglumetad methionil, a novel metabotropic glutamate 2/3 receptor agonist peptide prodrug. | 2015-05 |
|
| The quality of reporting of phase II and III trials for new antipsychotics: a systematic review. | 2015-02 |
|
| 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). | 2015-01 |
|
| When is a Proof-of-Concept (POC) not a POC? Pomaglumetad (LY2140023) as a Case Study for Antipsychotic Efficacy. | 2015 |
|
| A Double-Blind, Placebo-Controlled Comparator Study of LY2140023 monohydrate in patients with schizophrenia. | 2014-12-10 |
|
| 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. | 2014-10 |
|
| Pomaglumetad Methionil (LY2140023 Monohydrate) and Aripiprazole in Patients with Schizophrenia: A Phase 3, Multicenter, Double-Blind Comparison. | 2014 |
|
| Pomaglumetad methionil: no significant difference as an adjunctive treatment for patients with prominent negative symptoms of schizophrenia compared to placebo. | 2013-11 |
|
| Glutamate modulators as potential therapeutic drugs in schizophrenia and affective disorders. | 2013-08 |
|
| 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. | 2013-05-22 |
|
| 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). | 2013-04 |
|
| An agonist at glutamate and dopamine D2 receptors, LY404039. | 2013-03 |
|
| 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). | 2008-07 |
|
| 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). | 2007-04 |
|
| 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. | 2007-01-25 |
Sample Use Guides
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
| Substance Class |
Chemical
Created
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