Pomaglumetad methionil

Pomaglumetad methionil (INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name; developmental code names LY-2140023 and LY-2812223) is a metabotropic glutamate mGlu₂ and mGlu₃ receptor agonist which is or was under development for the treatment of schizophrenia, substance-related disorders, and post-traumatic stress disorder (PTSD).^[1][2] It is taken orally.^[1][2]

Pomaglumetad methionil

Clinical data
Other names	LY-2140023; LY2140023; LY-2812223; LY2812223; Pomaglumetad prodrug; LY-404039 prodrug; DB-103; DB103
Routes of administration	Oral[1][2]
Drug class	Metabotropic glutamate mGlu2 and mGlu3 receptor agonist
ATC code	None
Pharmacokinetic data
Bioavailability	49%[2]
Protein binding	Minimal[2]
Elimination half-life	1.5–2.4 hours[2] Pomaglumetad: 2–6.2 hours[2]
Identifiers
IUPAC name (1R,4S,5S,6S)-4-{{#parsoidfragment:2}}(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-2,2-dioxo-2λ6-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid
CAS Number	635318-55-7
PubChem CID	25195354
DrugBank	DB05096
ChemSpider	28530777
UNII	3V85EZ3KFQ
KEGG	D10896
ChEMBL	ChEMBL2110730
CompTox Dashboard (EPA)	DTXSID00212944
Chemical and physical data
Formula	C12H18N2O7S2
Molar mass	366.40 g·mol−1
3D model (JSmol)	Interactive image
SMILES CSCC[C@@H](C(=O)N[C@]1(CS(=O)(=O)[C@@H]2[C@H]1[C@H]2C(=O)O)C(=O)O)N
InChI 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 Key:VOYCNOJFAJAILW-CAMHOICYSA-N

Pharmacology

The drug is an inactive prodrug of pomaglumetad (LY-404039), which acts as a highly selective metabotropic glutamate mGlu₂ and mGlu₃ receptor agonist.^[2] Whereas the oral bioavailability of pomaglumetad was found to be low in humans, pomaglumetad methionil has an estimated oral bioavailability of approximately 49%.^[2] The drug is transported by the peptide transporter 1 (PepT1), resulting in it being rapidly and efficiently absorbed, and is then hydrolyzed into pomaglumetad.^[2] The elimination half-life of pomaglumetad methionil is 1.5 to 2.4 hours, whereas the half-life of pomaglumetad is 2 to 6.2 hours.^[2]

Development

Pomaglumetad methionil was under development by Eli Lilly and Company, Denovo Biopharma, and other institutions.^[1][3] As of January 2025, no recent development has been reported for treatment of schizophrenia or substance-related disorders, whereas development has been discontinued for PTSD.^[1][3] The highest developmental stage that pomaglumetad methionil has reached is phase 2 clinical trials.^[1][3]

See also

• Pomaglumetad § Pomaglumetad methionil
• Eglumetad and talaglumetad