daridorexant   Click here for help

GtoPdb Ligand ID: 11648

Synonyms: ACT-541468 | ACT541468 | nemorexant (former name) | Quviviq®
Approved drug PDB Ligand
daridorexant is an approved drug (FDA & EMA (2022))
Compound class: Synthetic organic
Comment: Daridorexant (ACT-541468) is a dual orexin receptor antagonist [4-5]. It was designed and developed for potential to treat insomnia [1-3,7-8].
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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 5
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 88.41
Molecular weight 450.16
XLogP 4.57
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 COc1ccc(c(c1)C(=O)N1CCC[C@@]1(C)c1nc2c([nH]1)ccc(c2C)Cl)n1nccn1
Isomeric SMILES Cc1c(ccc2c1nc([nH]2)[C@@]1(CCCN1C(=O)c1c(ccc(c1)OC)n1nccn1)C)Cl
InChI InChI=1S/C23H23ClN6O2/c1-14-17(24)6-7-18-20(14)28-22(27-18)23(2)9-4-12-29(23)21(31)16-13-15(32-3)5-8-19(16)30-25-10-11-26-30/h5-8,10-11,13H,4,9,12H2,1-3H3,(H,27,28)/t23-/m0/s1
InChI Key NBGABHGMJVIVBW-QHCPKHFHSA-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. Dauvilliers Y, Zammit G, Fietze I, Mayleben D, Seboek Kinter D, Pain S, Hedner J. (2020)
Daridorexant, a New Dual Orexin Receptor Antagonist to Treat Insomnia Disorder.
Ann Neurol, 87 (3): 347-356. [PMID:31953863]
2. Gehin M, Wierdak J, Sabattini G, Sidharta PN, Dingemanse J. (2022)
Effect of gastric pH and of a moderate CYP3A4 inducer on the pharmacokinetics of daridorexant, a dual orexin receptor antagonist.
Br J Clin Pharmacol, 88 (2): 810-819. [PMID:34371524]
3. Molano JRV. (2020)
Daridorexant: A new medication for insomnia in older adults?.
Neurology, 94 (21): e2287-e2289. [PMID:32451342]
4. Rappas M, Ali AAE, Bennett KA, Brown JD, Bucknell SJ, Congreve M, Cooke RM, Cseke G, de Graaf C, Doré AS et al.. (2020)
Comparison of Orexin 1 and Orexin 2 Ligand Binding Modes Using X-ray Crystallography and Computational Analysis.
J Med Chem, 63 (4): 1528-1543. [PMID:31860301]
5. Roch C, Bergamini G, Steiner MA, Clozel M. (2021)
Nonclinical pharmacology of daridorexant: a new dual orexin receptor antagonist for the treatment of insomnia.
Psychopharmacology (Berl), 238 (10): 2693-2708. [PMID:34415378]
6. Treiber A, de Kanter R, Roch C, Gatfield J, Boss C, von Raumer M, Schindelholz B, Muehlan C, van Gerven J, Jenck F. (2017)
The Use of Physiology-Based Pharmacokinetic and Pharmacodynamic Modeling in the Discovery of the Dual Orexin Receptor Antagonist ACT-541468.
J Pharmacol Exp Ther, 362 (3): 489-503. [PMID:28663311]
7. Ufer M, Kelsh D, Schoedel KA, Dingemanse J. (2022)
Abuse potential assessment of the new dual orexin receptor antagonist daridorexant in recreational sedative drug users as compared to suvorexant and zolpidem.
Sleep, 45 (3). [PMID:34480579]
8. Zammit G, Dauvilliers Y, Pain S, Sebök Kinter D, Mansour Y, Kunz D. (2020)
Daridorexant, a new dual orexin receptor antagonist, in elderly subjects with insomnia disorder.
Neurology, 94 (21): e2222-e2232. [PMID:32341187]