SRX246   Click here for help

GtoPdb Ligand ID: 12262

Synonyms: compound 50 [PMID: 17234419] [3] | SRX 246 | SRX-246
Compound class: Synthetic organic
Comment: SRX246 is an orally bioavailable, selective vasopressin V1A receptor antagonist [3]. Structurally it is a β-lactam derivative with an azetidone ring as its core pharmacophore. In rat studies it is able to cross the blood-brain barrier [2]. In humans SRX246 blocks the actions of intranasal AVP on aggression/fear circuits (in a MRI study) [5].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
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 10
Hydrogen bond donors 1
Rotatable bonds 15
Topological polar surface area 102.5
Molecular weight 731.4
XLogP 6.04
No. Lipinski's rules broken 2

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 O=C([C@H](N1C(=O)[C@H]([C@H]1/C=C/c1ccccc1)N1C(=O)OC[C@@H]1c1ccccc1)CC(=O)N1CCC(CC1)CCN1CCCCC1)N[C@H](c1ccccc1)C
Isomeric SMILES C[C@H](NC(=O)[C@@H](CC(=O)N1CCC(CCN2CCCCC2)CC1)N1[C@H](/C=C/c2ccccc2)[C@H](N2[C@H](COC2=O)c2ccccc2)C1=O)c1ccccc1
InChI InChI=1S/C44H53N5O5/c1-32(35-16-8-3-9-17-35)45-42(51)38(30-40(50)47-28-23-34(24-29-47)22-27-46-25-12-5-13-26-46)48-37(21-20-33-14-6-2-7-15-33)41(43(48)52)49-39(31-54-44(49)53)36-18-10-4-11-19-36/h2-4,6-11,14-21,32,34,37-39,41H,5,12-13,22-31H2,1H3,(H,45,51)/b21-20+/t32-,37+,38+,39+,41-/m0/s1
InChI Key HKPLAUMYFHPXIC-KRESLXGLSA-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/)
References
1. Brownstein MJ, Simon NG, Long JD, Yankey J, Maibach HT, Cudkowicz M, Coffey C, Conwit RA, Lungu C, Anderson KE et al.. (2020)
Safety and Tolerability of SRX246, a Vasopressin 1a Antagonist, in Irritable Huntington's Disease Patients-A Randomized Phase 2 Clinical Trial.
J Clin Med, 9 (11): 3682. [PMID:33207828]
2. Fabio K, Guillon C, Lacey CJ, Lu SF, Heindel ND, Ferris CF, Placzek M, Jones G, Brownstein MJ, Simon NG. (2012)
Synthesis and evaluation of potent and selective human V1a receptor antagonists as potential ligands for PET or SPECT imaging.
Bioorg Med Chem, 20 (3): 1337-45. [PMID:22249122]
3. Guillon CD, Koppel GA, Brownstein MJ, Chaney MO, Ferris CF, Lu SF, Fabio KM, Miller MJ, Heindel ND, Hunden DC et al.. (2007)
Azetidinones as vasopressin V1a antagonists.
Bioorg Med Chem, 15 (5): 2054-80. [PMID:17234419]
4. Lago TR, Brownstein MJ, Page E, Beydler E, Manbeck A, Beale A, Roberts C, Balderston N, Damiano E, Pineles SL et al.. (2021)
The novel vasopressin receptor (V1aR) antagonist SRX246 reduces anxiety in an experimental model in humans: a randomized proof-of-concept study.
Psychopharmacology (Berl), 238 (9): 2393-2403. [PMID:33970290]
5. Lee RJ, Coccaro EF, Cremers H, McCarron R, Lu SF, Brownstein MJ, Simon NG. (2013)
A novel V1a receptor antagonist blocks vasopressin-induced changes in the CNS response to emotional stimuli: an fMRI study.
Front Syst Neurosci, 7: 100. [PMID:24376401]
6. Maibach HT, Brownstein MJ, Hersch SM, Anderson KE, Itzkowitz DE, Damiano EM, Simon NG. (2022)
The Vasopressin 1a Receptor Antagonist SRX246 Reduces Aggressive Behavior in Huntington's Disease.
J Pers Med, 12 (10). [PMID:36294700]