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dasotraline   Click here for help

GtoPdb Ligand ID: 8308

Synonyms: (1R,4S)-trans-norsertraline | SEP-225,289 | SEP-225289
Compound class: Synthetic organic
Comment: Dasotraline is a triple reuptake inhibitor [1,3]. Such compounds are also known as serotonin-norepinephrine-dopamine reuptake inhibitors, or SNDRIs. Structurally, dasotraline is a stereoisomer of an active metabolite of sertraline, a selective serotonin reuptake inhibitor (SSRI) antidepressant.
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 1
Hydrogen bond donors 1
Rotatable bonds 1
Topological polar surface area 26.02
Molecular weight 291.06
XLogP 4.75
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES NC1CCC(c2c1cccc2)c1ccc(c(c1)Cl)Cl
Isomeric SMILES N[C@@H]1CC[C@H](c2c1cccc2)c1ccc(c(c1)Cl)Cl
InChI InChI=1S/C16H15Cl2N/c17-14-7-5-10(9-15(14)18)11-6-8-16(19)13-4-2-1-3-12(11)13/h1-5,7,9,11,16H,6,8,19H2/t11-,16+/m0/s1
InChI Key SRPXSILJHWNFMK-MEDUHNTESA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Bioactivity Comments
To date, IC50 values for the inhibition of monoamine transporters by dasotraline has only been reported in a meeting abstract (Schreiber R, Lew R, Hardy L, Cremers T, et al (2009) Pharmacological characterization of the triple monoamine transporter inhibitor SEP-225289. Society for Neuroscience (Abstract no. 549.8/X2)). IC50s for inhibiton of rat SERT, NET and DAT are 11, 6 and 4nM respectively.
In vivo drug occupancy has been evaluated as a more accurate indication of a drug's transporter binding profile. PET results show that dasotraline ocupies ~85% of dopamine transporter sites, whereas serotonin transporter occupancy was too low to calculate accurately [2]. This result is despite in vitro binding to each transporter being similar.