Pomaglumetad

WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 319774

CAS#: 635318-11-5

Description: Pomaglumetad, also known as LY-404,039, is a highly selective agonist for the metabotropic glutamate receptor group II subtypes mGluR2 and mGluR3. Pomaglumetad has potential antipsychotic and anxiolytic effects. LY-404,039 is intended as a treatment for schizophrenia and other psychotic and anxiety disorders by modulating glutamatergic activity and reducing presynaptic release of glutamate at synapses in limbic and forebrain areas relevant to these disorders. The specific binding of LY-404,039 to human cloned mGlu receptors has been found to be highest for mGluR2 (Ki = 149 +/- 11 nM) and relatively high for mGluR3 (Ki = 92 +/-14 nM).

Chemical Structure

Pomaglumetad

CAS# 635318-11-5

Instruction

Theoretical Analysis

MedKoo Cat#: 319774
Name: Pomaglumetad
CAS#: 635318-11-5
Chemical Formula: C7H9NO6S
Exact Mass: 235.02
Molecular Weight: 235.210
Elemental Analysis: C, 35.75; H, 3.86; N, 5.96; O, 40.81; S, 13.63

Price and Availability

Size	Price	Availability	Quantity
10mg	USD -2
25mg	USD -2
50mg	USD -2
100mg	USD -2
200mg	USD -2
500mg	USD -2
1g	USD -1
2g	USD -1
5g	USD -1
10g	USD -1
20g	USD -1
50g	USD -1
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: LY-404039; LY 404039; LY404039; LY-404,039; LY404,039; LY 404,039; Pomaglumetad

IUPAC/Chemical Name: (1R,4S,5S,6S)-4-amino-2-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid 2,2-dioxide

InChi Key: AVDUGNCTZRCAHH-MDASVERJSA-N

InChi Code: InChI=1S/C7H9NO6S/c8-7(6(11)12)1-15(13,14)4-2(3(4)7)5(9)10/h2-4H,1,8H2,(H,9,10)(H,11,12)/t2-,3-,4+,7+/m1/s1

SMILES Code: O=S1(C[C@](C(O)=O)(N)[C@@H]2[C@@H](C(O)=O)[C@@H]21)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: Human studies investigating therapeutic use of LY-404,039 have focused on the prodrug LY-2140023, a methionine amide of LY-404,039 (also called pomaglumetad methionil or LY-2140023 monohydrate) since LY-404,039 exhibits low oral absorption and bioavailability in humans. Early human trials using this prodrug form of LY-404,039 gave encouraging results. However, pharmaceutical company Eli Lilly terminated further development of the compound in 2012 after it failed in phase II clinical trials. In September 2013, the results of a randomized, placebo-controlled clinical trial investigating the impact of adjunctive LY-2140023 on prominent negative symptoms in schizophrenia was published and failed to demonstrate any benefit. https://en.wikipedia.org/wiki/LY-404,039

Instruction:

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Biological target:
In vitro activity:
In vivo activity:

Preparing Stock Solutions

The following data is based on the product molecular weight 235.21 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:
In vitro protocol:
In vivo protocol:

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1: Moulton RD, Ruterbories KJ, Bedwell DW, Mohutsky MA. In vitro characterization of the bioconversion of pomaglumetad methionil, a novel metabotropic glutamate 2/3 receptor agonist peptide prodrug. Drug Metab Dispos. 2015 May;43(5):756-61. doi: 10.1124/dmd.114.062893. Epub 2015 Mar 9. PubMed PMID: 25755052.

2: Annes WF, Long A, Witcher JW, Ayan-Oshodi MA, Knadler MP, Zhang W, Mitchell MI, Cornelissen K, Hall SD. 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). J Pharm Sci. 2015 Jan;104(1):207-14. doi: 10.1002/jps.24226. Epub 2014 Nov 7. PubMed PMID: 25382826.

3: Wyckhuys T, Wyffels L, Langlois X, Schmidt M, Stroobants S, Staelens S. The [18F]FDG μPET readout of a brain activation model to evaluate the metabotropic glutamate receptor 2 positive allosteric modulator JNJ-42153605. J Pharmacol Exp Ther. 2014 Aug;350(2):375-86. doi: 10.1124/jpet.114.213959. Epub 2014 Jun 4. PubMed PMID: 24898267.

4: Megens AA, Hendrickx HM, Hens KA, Talloen WJ, Lavreysen H. mGlu(2) receptor-mediated modulation of conditioned avoidance behavior in rats. Eur J Pharmacol. 2014 Mar 15;727:130-9. doi: 10.1016/j.ejphar.2014.01.044. Epub 2014 Jan 30. PubMed PMID: 24486391.

5: Seeman P. An agonist at glutamate and dopamine D2 receptors, LY404039. Neuropharmacology. 2013 Mar;66:87-8. doi: 10.1016/j.neuropharm.2012.07.001. Epub 2012 Jul 4. PubMed PMID: 22884896.

6: Lowe S, Dean R, Ackermann B, Jackson K, Natanegara F, Anderson S, Eckstein J, Yuen E, Ayan-Oshodi M, Ho M, McKinzie D, Perry K, Svensson K. Effects of a novel mGlu₂/₃ receptor agonist prodrug, LY2140023 monohydrate, on central monoamine turnover as determined in human and rat cerebrospinal fluid. Psychopharmacology (Berl). 2012 Feb;219(4):959-70. doi: 10.1007/s00213-011-2427-9. Epub 2011 Aug 17. PubMed PMID: 21847569.

7: Siok CJ, Cogan SM, Shifflett LB, Doran AC, Kocsis B, Hajós M. Comparative analysis of the neurophysiological profile of group II metabotropic glutamate receptor activators and diazepam: effects on hippocampal and cortical EEG patterns in rats. Neuropharmacology. 2012 Jan;62(1):226-36. doi: 10.1016/j.neuropharm.2011.07.011. Epub 2011 Jul 26. PubMed PMID: 21791219.

8: Durand D, Carniglia L, Caruso C, Lasaga M. Reduced cAMP, Akt activation and p65-c-Rel dimerization: mechanisms involved in the protective effects of mGluR3 agonists in cultured astrocytes. PLoS One. 2011;6(7):e22235. doi: 10.1371/journal.pone.0022235. Epub 2011 Jul 14. PubMed PMID: 21779400; PubMed Central PMCID: PMC3136520.

9: Dedeurwaerdere S, Wintmolders C, Straetemans R, Pemberton D, Langlois X. Memantine-induced brain activation as a model for the rapid screening of potential novel antipsychotic compounds: exemplified by activity of an mGlu2/3 receptor agonist. Psychopharmacology (Berl). 2011 Mar;214(2):505-14. doi: 10.1007/s00213-010-2052-z. Epub 2010 Oct 31. PubMed PMID: 21057775.

10: Mezler M, Geneste H, Gault L, Marek GJ. LY-2140023, a prodrug of the group II metabotropic glutamate receptor agonist LY-404039 for the potential treatment of schizophrenia. Curr Opin Investig Drugs. 2010 Jul;11(7):833-45. PubMed PMID: 20571979.

11: Seeman P, Guan HC. Glutamate agonist LY404,039 for treating schizophrenia has affinity for the dopamine D2(High) receptor. Synapse. 2009 Oct;63(10):935-9. doi: 10.1002/syn.20704. PubMed PMID: 19588471.

12: Lebois EP. Neither typical nor atypical: LY404039 provides proof of concept that selective targeting of mGluR2/3 receptors is a valid mechanism for obtaining antipsychotic efficacy. Curr Top Med Chem. 2008;8(16):1480-1. PubMed PMID: 19006848.

13: Fell MJ, Svensson KA, Johnson BG, Schoepp DD. 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). J Pharmacol Exp Ther. 2008 Jul;326(1):209-17. doi: 10.1124/jpet.108.136861. Epub 2008 Apr 18. PubMed PMID: 18424625.

14: Seeman P. Glutamate agonists for schizophrenia stimulate dopamine D2High receptors. Schizophr Res. 2008 Feb;99(1-3):373-4. PubMed PMID: 18077139.

15: Patil ST, Zhang L, Martenyi F, Lowe SL, Jackson KA, Andreev BV, Avedisova AS, Bardenstein LM, Gurovich IY, Morozova MA, Mosolov SN, Neznanov NG, Reznik AM, Smulevich AB, Tochilov VA, Johnson BG, Monn JA, Schoepp DD. Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial. Nat Med. 2007 Sep;13(9):1102-7. Epub 2007 Sep 2. Erratum in: Nat Med. 2007 Oct;13(10):1264. PubMed PMID: 17767166.

16: Rorick-Kehn LM, Johnson BG, Knitowski KM, Salhoff CR, Witkin JM, Perry KW, Griffey KI, Tizzano JP, Monn JA, McKinzie DL, Schoepp DD. In vivo pharmacological characterization of the structurally novel, potent, selective mGlu2/3 receptor agonist LY404039 in animal models of psychiatric disorders. Psychopharmacology (Berl). 2007 Jul;193(1):121-36. Epub 2007 Mar 24. PubMed PMID: 17384937.

17: Monn JA, Massey SM, Valli MJ, Henry SS, Stephenson GA, Bures M, Hérin M, Catlow J, Giera D, Wright RA, Johnson BG, Andis SL, Kingston A, Schoepp DD. 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. J Med Chem. 2007 Jan 25;50(2):233-40. PubMed PMID: 17228865.

18: Rorick-Kehn LM, Johnson BG, Burkey JL, Wright RA, Calligaro DO, Marek GJ, Nisenbaum ES, Catlow JT, Kingston AE, Giera DD, Herin MF, Monn JA, McKinzie DL, Schoepp DD. 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). J Pharmacol Exp Ther. 2007 Apr;321(1):308-17. Epub 2007 Jan 4. PubMed PMID: 17204749.

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