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Pomaglumetad methionil

Denovo Biopharma

Drug Names(s): DB103, LY2140023, LY-2140023, mGlu2/3 prodrug

Description: LY2140023 is a peptide prodrug of the mGlu2/3 agonist LY404039. mGluR2/3 are generally pre-synaptic receptors (they are also found on glial cells) where they modulate glutamate release. Agonists of the receptor have also been found to reduce dopamine release. Finally, these receptors may may form a complex with 5-HT2A receptors, suggesting they can regulate5-HT signalling. They are highly expressed in the hippocampus, amygdala, and prefrontal cortex, areas associated with neuropsychiatric disorders such as drug abuse, anxiety, and schizophrenia.

Key receptor affinities for LY404039 include:
mGlu2: 99 nM;
mGlu3: 94 nM;
mGlu6: 14400 nM;
mGlu7: 28800 nM;
mGlu8: 11200 nM.

Lilly reports that LY404039's dissociation constants for iontrophic glutamate receptors (NMDA, AMPA, Kainate), monoamine (D1, D2, and 5-HT2), adrenergic (alpha-1, alpha-2, and beta), histamine H1, and muscarinic receptors are all greater than 100 uM. Others have published data suggesting that LY404039 has significant affinity for D2 receptors, a classical and well-established anti-psychotic drug target.

Deal Structure: Denovo and Eli Lilly
In March 2015, Denovo announced that it has exclusively licensed pomaglumetad methionil (mGlu2/3 receptor agonist) for schizophrenia from Eli Lilly and Company. Denovo gains all rights to develop, manufacture and commercialize pomaglumetad globally, including transfer of all intellectual property and other rights, data, and information. Lilly has an option to re-acquire pomaglumetad upon a successful clinical trial, for predetermined undisclosed financial terms.


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