E-52862, also known as sigma-1 receptor antagonist (S1A, S1RA), as well as MR-309, is a
selective sigma-1 receptor
The sigma-1 receptor (σ1R), one of two sigma receptor subtypes, is a chaperone protein at the endoplasmic reticulum (ER) that modulates calcium signaling through the IP3 receptor. In humans, the σ1 receptor is encoded by the ''SIGMAR1'' gen ...
antagonist, with a reported
binding affinity
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a m ...
of ''K''
i = 17.0 ± 7.0 nM, selective over the
sigma-2 receptor
The sigma-2 receptor (σ2R) is a sigma receptor subtype that has attracted attention due to its involvement in diseases such as cancer and neurological diseases. It is currently under investigation for its potential diagnostic and therapeutic use ...
and against a panel of other 170 receptors, enzymes, transporters and ion channels.
In preclinical studies, S1RA has demonstrated efficacy in relieving
neuropathic pain
Neuropathic pain is pain caused by damage or disease affecting the somatosensory system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous ...
and
pain in other sensitizing conditions, associated with an improvement of the emotional negative state.
S1RA is being developed by
Esteve
Esteve is a Spanish international pharmaceutical company headquartered in Barcelona
Barcelona ( , , ) is a city on the coast of northeastern Spain. It is the capital and largest city of the autonomous community of Catalonia, as well as the ...
for the treatment of
neuropathic pain
Neuropathic pain is pain caused by damage or disease affecting the somatosensory system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous ...
and the potentiation of opioid analgesia and has successfully completed Phase I clinical trials showing good safety and tolerability, and a pharmacokinetic profile compatible with once a day oral administration.
Phase II clinical trials are currently underway, making S1RA the first selective
sigma-1 receptor
The sigma-1 receptor (σ1R), one of two sigma receptor subtypes, is a chaperone protein at the endoplasmic reticulum (ER) that modulates calcium signaling through the IP3 receptor. In humans, the σ1 receptor is encoded by the ''SIGMAR1'' gen ...
antagonist evaluated in humans for these conditions.
See also
*
List of investigational analgesics
This is a list of investigational analgesics, or analgesics that are currently under development for clinical use but are not yet approved. ''Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in pare ...
References
External links
(Compound datasheet in
Esteve
Esteve is a Spanish international pharmaceutical company headquartered in Barcelona
Barcelona ( , , ) is a city on the coast of northeastern Spain. It is the capital and largest city of the autonomous community of Catalonia, as well as the ...
company website)
E-52862 - AdisInsight
4-Morpholinyl compunds
2-Naphthyl compounds
Pyrazoles
Sigma antagonists
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