ulotaront   Click here for help

GtoPdb Ligand ID: 10454

Synonyms: example 129 [WO2011069063A2] [6] | SEP-363856 (parent molecule) | SEP-856 | SEP363856
PDB Ligand
Compound class: Synthetic organic
Comment: Ulotaront (SEP-363856) is an orally active and brain-penetrant psychotropic agent with a novel mechanism of action. It acts as a trace amine-associated receptor 1 (TAAR1) agonist with additional 5-HT1A receptor agonist activity, and agonism at both of these receptors appears to be required for its clinical effects [2-3]. SEP-363856 is being developed by Sunovion Pharmaceuticals and PsychoGenics, and was granted FDA Breakthrough Therapy Designation as an anti-schizophrenia therapeutic in May 2019. The lack of D2 receptor activity distinguishes SEP-363856 from current antipsychotic medications.
In the Dedic et al. article from 2019 SEP-363856 refers to the hydrochloride salt. We show the parent molecule here. This S enantiomer is more active at TAAR1 compared to the R stereoenantiomer [2].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 2
Hydrogen bond donors 1
Rotatable bonds 2
Topological polar surface area 49.5
Molecular weight 183.07
XLogP 0.51
No. Lipinski's rules broken 0
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Canonical SMILES CNCC1OCCc2c1scc2
Isomeric SMILES CNC[C@@H]1OCCc2c1scc2
InChI InChI=1S/C9H13NOS/c1-10-6-8-9-7(2-4-11-8)3-5-12-9/h3,5,8,10H,2,4,6H2,1H3/t8-/m0/s1
Bioactivity Comments
SEP-363856 is devoid of D2 receptor activity [2]. Weak partial agonist activity was detected in assays of the 5-HT1B, 5-HT1D and 5-HT7 receptors. No 5-HT2B agonist activity, and little/no 5-HT2A agonist activity was measurable.
Selectivity at GPCRs
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
TA1 receptor Primary target of this compound Hs Agonist Agonist 6.8 pIC50 - 2
pIC50 6.8 (IC50 1.4x10-7 M) [2]
5-HT1A receptor Hs Agonist Agonist 5.6 pIC50 - 2
pIC50 5.6 (IC50 2.3x10-6 M) [2]