Daridorexant
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Also known as Act-541468DEA NO. 2410NemorexantDaridorexant
Summary
Daridorexant (CHEMBL4297590) is an approved small molecule (ATC N05CJ03) targeting HCRTR1 and HCRTR2; indicated across 6 conditions including insomnia and post-traumatic stress disorder.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: N05CJ03
- Targets: 2 (HCRTR1, HCRTR2)
- Indications: 6 conditions
- Clinical trials: 43
- Chemistry: 450.9 Da · C23H23ClN6O2
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL4297590 |
| Name | Daridorexant |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 91801202 |
| ATC | N05CJ03 |
| Molecular formula | C23H23ClN6O2 |
| Molecular weight | 450.9 |
| InChIKey | NBGABHGMJVIVBW-QHCPKHFHSA-N |
SMILES: CC1=C(C=CC2=C1N=C(N2)[C@@]3(CCCN3C(=O)C4=C(C=CC(=C4)OC)N5N=CC=N5)C)Cl
IUPAC name: [(2S)-2-(5-chloro-4-methyl-1H-benzimidazol-2-yl)-2-methylpyrrolidin-1-yl]-[5-methoxy-2-(triazol-2-yl)phenyl]methanone
Also known as: Act-541468, ACT-541468, Daridorexant, DEA NO. 2410, Nemorexant, DARIDOREXANT, Daridorexant; Nemorexant
Parent form; salt/anhydrous children: CHEMBL4650216
Patent coverage: 42 distinct patent families (102 SureChEMBL compound mentions), from 3 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.
Targets
Targets
Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| HCRTR1 | OX1 receptor | Antagonist | 9.5 | 4.9% | O43613 |
| HCRTR2 | OX2 receptor | Antagonist | 9.2 | O43614 |
Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Orexin receptor type 2, Orexin/Hypocretin receptor type 1.
Bioactivity
ChEMBL activities: 10 potent at pChembl ≥ 5 of 10 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| HCRTR1 | 9.22 | IC50 | 0.6 | nM | CHEMBL_ACT_29106210 |
| HCRTR2 | 9.05 | IC50 | 0.9 | nM | CHEMBL_ACT_29106212 |
| HCRTR1 | 8.96 | IC50 | 1.1 | nM | CHEMBL_ACT_26123580 |
| HCRTR2 | 8.9 | Ki | 1.26 | nM | CHEMBL_ACT_19153620 |
| HCRTR1 | 8.8 | Ki | 1.58 | nM | CHEMBL_ACT_19153608 |
| HCRTR2 | 8.77 | IC50 | 1.7 | nM | CHEMBL_ACT_26123582 |
| HCRTR1 | 8.7 | IC50 | 2 | nM | CHEMBL_ACT_27256943 |
| HCRTR1 | 8.7 | IC50 | 2 | nM | CHEMBL_ACT_27526187 |
| HCRTR2 | 8.52 | IC50 | 3 | nM | CHEMBL_ACT_27256946 |
| HCRTR2 | 8.52 | IC50 | 3 | nM | CHEMBL_ACT_27526190 |
Target pathways
Aggregated over 2 target gene(s): HCRTR1, HCRTR2.
Top Reactome pathways
2 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Orexin and neuropeptides FF and QRFP bind to their respective receptors | 2 | HCRTR1, HCRTR2 |
| G alpha (q) signalling events | 2 | HCRTR1, HCRTR2 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| neuropeptide signaling pathway | 2 |
| chemical synaptic transmission | 2 |
| feeding behavior | 2 |
| cellular response to hormone stimulus | 2 |
| regulation of cytosolic calcium ion concentration | 2 |
| signal transduction | 2 |
| G protein-coupled receptor signaling pathway | 2 |
| positive regulation of ERK1 and ERK2 cascade | 1 |
| phospholipase C-activating G protein-coupled receptor signaling pathway | 1 |
| regulation of circadian sleep/wake cycle, wakefulness | 1 |
| circadian sleep/wake cycle process | 1 |
| locomotion | 1 |
| glucose homeostasis | 1 |
Indications & clinical
Indications
6 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).
| Indication | Trial phase | MONDO | EFO |
|---|---|---|---|
| insomnia | 3 | MONDO:0013600 | EFO:0004698 |
| post-traumatic stress disorder | 2 | MONDO:0005146 | EFO:0001358 |
| chronic obstructive pulmonary disease | 1 | MONDO:0005002 | EFO:0000341 |
| liver disorder | 1 | MONDO:0005154 | EFO:0001421 |
| obstructive sleep apnea syndrome | 1 | MONDO:0007147 | EFO:0003918 |
| kidney failure | 1 | MONDO:0001106 | HP:0000083 |
Clinical trials
Total trials: 43.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE1 | 22 |
| PHASE2 | 7 |
| PHASE4 | 6 |
| PHASE3 | 5 |
| Not specified | 3 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT05924425 | PHASE4 | RECRUITING | Daridorexant to Treat Insomnia in Patients With Mild Cognitive Impairment and Mild to Moderate Alzheimer Disease |
| NCT07136415 | PHASE4 | RECRUITING | Comparing Digital Therapy, Trazodone, and Daridorexant for Menopause-Related Insomnia Symptoms |
| NCT07267559 | PHASE4 | RECRUITING | Dual Orexin Antagonism and Emotion and Affective Processing Study |
| NCT07328594 | PHASE4 | NOT_YET_RECRUITING | Impact of Daridorexant on Sleep, Daytime Alertness, and Smoking |
| NCT07555743 | PHASE4 | NOT_YET_RECRUITING | Efficacy and Safety of Daridorexant in Patients With Major Depressive Disorder and Insomnia |
| NCT05597020 | PHASE4 | COMPLETED | A Study to Find Out if Daridorexant is Safe and Efficacious in Patients With Insomnia and Comorbid Nocturia |
| NCT03545191 | PHASE3 | COMPLETED | Study to Assess the Efficacy and Safety of ACT-541468 (Daridorexant) in Adult and Elderly Subjects With Insomnia Disorder |
| NCT03575104 | PHASE3 | COMPLETED | Study to Assess the Efficacy and Safety of ACT-541468 (Daridorexant) in Adult and Elderly Subjects Suffering From Difficulties to Sleep |
| NCT03679884 | PHASE3 | COMPLETED | Study to Assess the Long Term Safety and Tolerability of ACT-541468 (Daridorexant) in Adult and Elderly Subjects Suffering From Difficulties to Sleep |
| NCT06010693 | PHASE3 | COMPLETED | A Study of Daridorexant in Chinese Patients With Insomnia Disorder |
| NCT07028697 | PHASE3 | COMPLETED | A Study to Evaluate the Efficacy and Safety of Daridorexant in Participants With Insomnia Disorder |
| NCT07213349 | PHASE2 | RECRUITING | Daridorexant for Alzheimer Disease Prevention |
| NCT07217912 | PHASE2 | RECRUITING | Daridorexant to Prevent Post-cardiotomy Delirium |
| NCT07532252 | PHASE2 | NOT_YET_RECRUITING | Daridorexant for Alcohol Use Disorder |
| NCT02839200 | PHASE2 | COMPLETED | Efficacy and Safety of ACT-541468 in Adult Subjects With Insomnia Disorder |
| NCT02841709 | PHASE2 | COMPLETED | Efficacy and Safety of ACT-541468 in Elderly Subjects With Insomnia Disorder |
| NCT05423717 | PHASE2 | COMPLETED | Dose-finding Study Assessing the Efficacy, Safety, and Pharmacokinetics of Daridorexant in Subjects Aged 10 to < 18 Years With Insomnia Disorder |
| NCT06630390 | PHASE2 | COMPLETED | Daridorexant to Prevent Delirium After Heart Surgery |
| NCT02526888 | PHASE1 | COMPLETED | Pharmacokinetic Interaction Between Diltiazem and ACT-541468 in Healthy Subjects |
| NCT02919319 | PHASE1 | COMPLETED | A Single Ascending Dose Study of ACT-541468 in Healthy Male Subjects |
| NCT03017495 | PHASE1 | COMPLETED | A Clinical Study to Investigate the Potential Interactions Between Food and ACT-541468 and Between ACT-541468 and Midazolam |
| NCT03101189 | PHASE1 | COMPLETED | A Study of ACT-541468 in Healthy Japanese and Caucasian Subjects |
| NCT03339752 | PHASE1 | COMPLETED | A Study in Healthy Male Subjects to Investigate Whether Administration of ACT-541468 Can Affect the Fate in the Body (Amount and Time of Presence in the Blood) of Rosuvastatin |
| NCT03609775 | PHASE1 | COMPLETED | A Study to Investigate the Drug-drug Interactions Between ACT-541468 and Ethanol in Healthy Subjects |
| NCT03646864 | PHASE1 | COMPLETED | A Study to Evaluate the Effects of ACT-541468 on Respiration in Patients With Moderate Chronic Obstructive Pulmonary Disease |
| NCT03657355 | PHASE1 | COMPLETED | Study to Evaluate the Abuse Potential of ACT-541468 in Healthy Recreational Drug Users |
| NCT03713242 | PHASE1 | COMPLETED | A Study to Evaluate the Pharmacokinetics of ACT-541468 in Subjects With Mild, Moderate, and Severe Hepatic Impairment |
| NCT03765294 | PHASE1 | COMPLETED | A Study to Investigate the Effects of ACT-541468 on Nighttime Respiratory Function in Patients With Mild to Moderate Obstructive Sleep Apnea |
| NCT03799978 | PHASE1 | COMPLETED | A Clinical Study to Investigate the Food Effect on the Pharmacokinetics of ACT-541468 in Healthy Male Subjects |
| NCT03892902 | PHASE1 | COMPLETED | A Clinical Study to Assess Next-day Driving Performance Following Administration of ACT-541468 in Middle-aged and Elderly Subjects |
| NCT04024332 | PHASE1 | COMPLETED | Study of the Way the Body Takes up, Distributes, and Gets Rid of ACT-541468 in Subjects With Abnormal Kidney Function Compared to Healthy Subjects |
| NCT04250506 | PHASE1 | COMPLETED | A Study to Assess the Effect of Single Doses of Daridorexant on Electrocardiogram Parameters in Healthy Subjects |
| NCT04390334 | PHASE1 | COMPLETED | A Study in Healthy Male Subjects to Investigate the Effect of Famotidine and Efavirenz on the Way the Body Takes up, Distributes, and Gets Rid of Daridorexant. |
| NCT05458193 | PHASE1 | COMPLETED | A Study to Investigate the Effects of Daridorexant on Nighttime Breathing in Patients With Shallow or Paused Breath During Sleep |
| NCT05480475 | PHASE1 | COMPLETED | A Study to Examine the Effect of Daridorexant on the Way the Body Absorbs, Distributes, and Gets Rid of Dabigatran and Rosuvastatin in Healthy Male Subjects |
| NCT05480488 | PHASE1 | COMPLETED | A Study to Examine the Effect of Daridorexant on the Way the Body Absorbs, Distributes, and Gets Rid of Midazolam and Warfarin in Healthy Male Subjects |
| NCT05632393 | PHASE1 | COMPLETED | A Study to Measure Daridorexant in Breast Milk of Healthy Lactating Women |
| NCT05702177 | PHASE1 | COMPLETED | A Study of the Effect of Daridorexant on Nighttime Body Posture, the Noise Level Required to Wake up, and the Ability to Remember Words Previously Presented |
| NCT05877222 | PHASE1 | COMPLETED | A Phase 1 Trial to Investigate the Biological Equivalence of 5 × 10 mg Tablets and 2 × 25 mg Tablets of Daridorexant in Healthy Male and Female Japanese Participants |
| NCT06326723 | PHASE1 | COMPLETED | Investigate the PK, Safety, and Tolerability After Single and Multiple Dose Daridorexant in Chinese Healthy Subjects |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No PharmGKB pharmacogenomic data curated for this drug.
Related molecules
Related molecules
Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.
10 molecules share ≥1 primary target. Top 10 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| LEMBOREXANT | ChEMBL | Phase 4 (approved) | HCRTR1, HCRTR2 |
| SUVOREXANT | ChEMBL | Phase 4 (approved) | HCRTR1, HCRTR2 |
| ALMOREXANT | ChEMBL | Phase 3 | HCRTR1, HCRTR2 |
| SELTOREXANT | ChEMBL | Phase 3 | HCRTR1, HCRTR2 |
| FILOREXANT | ChEMBL | Phase 2 | HCRTR1, HCRTR2 |
| NIVASOREXANT | ChEMBL | Phase 2 | HCRTR1, HCRTR2 |
| SB-649868 | ChEMBL | Phase 2 | HCRTR1, HCRTR2 |
| NALFURAFINE | ChEMBL | Phase 4 (approved) | HCRTR1 |
| DANAVOREXTON | ChEMBL | Phase 2 | HCRTR2 |
| Belzutifan | PubChem | Approved | HCRTR1 |
Related Atlas pages
- Genes: HCRTR1, HCRTR2
- Diseases: insomnia
- Drugs: Lemborexant, Suvorexant, Almorexant, Seltorexant, Nalfurafine, Belzutifan