Seltorexant

Short description: Experimental anti-insomnia drug

Seltorexant

Clinical data
Other names| MIN-202; JNJ-42847922; JNJ-922
Routes of
administration| By mouth[1]
Drug class| Orexin antagonist
ATC code|

* None

Legal status
Legal status|

* US: Investigational New Drug

Pharmacokinetic data
Metabolism| CYP3A4[2]
Elimination half-life| 2–3 hours[2]
Identifiers

IUPAC name

* [5-(4,6-Dimethylpyrimidin-2-yl)-hexahydropyrrolo[3,4-c]pyrrol-2-yl]-(2-fluoro-6-[1,2,3]triazol-2-ylphenyl)methanone

CAS Number|

* 1293281-49-8 Y

PubChem CID|

* 67116280

ChemSpider|

* 34989176

UNII|

* AIS8N3O50B

KEGG|

* D11269

Chemical and physical data
Formula| C21H22FN7O
Molar mass| 407.453 g·mol−1
3D model (JSmol)|

* Interactive image

SMILES

* c4c(C)nc(nc4C)N5CC2CN(CC2C5)C(=O)c1c(cccc1F)-n3nccn3

InChI

* InChI=1S/C21H22FN7O/c1-13-8-14(2)26-21(25-13)28-11-15-9-27(10-16(15)12-28)20(30)19-17(22)4-3-5-18(19)29-23-6-7-24-29/h3-8,15-16H,9-12H2,1-2H3/t15-,16+

* Key:SQOCEMCKYDVLMM-IYBDPMFKSA-N

Seltorexant, also known by its developmental code names MIN-202 and JNJ-42847922, is an orexin antagonist medication which is under development for the treatment of depression and insomnia.[3][2] It is a selective antagonist of the orexin OX2 receptor (2-SORA).[2][4][1] The medication is taken by mouth.[1] As of February 2022, seltorexant is in phase 3 clinical trials for treatment of major depressive disorder (MDD) and phase 2 trials for treatment of insomnia.[3] It was also under investigation for the treatment of sleep apnea, but no recent development has been reported for this indication.[3] Seltorexant is under development by Minerva Neurosciences and Johnson & Johnson's Janssen Pharmaceuticals.[3]

Seltorexant is being explored at doses of 5 to 80 mg.[2] In the early clinical trials conducted so far, seltorexant has been found to improve depression scores on the Hamilton Depression Rating Scale in people with MDD and to improve sleep onset, total sleep time, time awake after sleep onset, and sleep efficiency in people with MDD and/or insomnia.[2][4] Seltorexant is reported to be safe and well-tolerated.[2][4] Side effects of seltorexant observed in clinical trials so far have included somnolence, fatigue, dizziness, headache, abdominal discomfort, and nightmares.[2]

Seltorexant shows over 100-fold greater binding affinity for the OX2 receptor over the OX1 receptor.[4] This is in contrast to other orexin receptor antagonists like suvorexant, lemborexant, and daridorexant, which are all dual orexin receptor antagonists (DORAs).[4][2] Seltorexant has fast absorption with a time to peak levels of 0.3 to 1.5 hours and has a relatively short duration with an elimination half-life of only 2 to 3 hours.[2][4] No residual effects of the medication were observed 4 hours after daytime administration.[2] The pharmacokinetics of seltorexant are considered to be ideal for sleep induction.[4] Seltorexant is metabolized by the cytochrome P450 enzyme CYP3A4.[2] It is a small-molecule compound and is structurally related to other clinically used orexin receptor antagonists.[5][2]

## See also

* Vornorexant – another investigational short-acting orexin receptor antagonist
* List of investigational antidepressants § Orexin receptor antagonists
* List of investigational sleep drugs § Orexin receptor antagonists

## References

1. ↑ 1.0 1.1 1.2 "Hypocretin/Orexin Receptor Pharmacology and Sleep Phases". Front Neurol Neurosci. Frontiers of Neurology and Neuroscience 45: 22–37. 2021. doi:10.1159/000514963. ISBN 978-3-318-06843-6. PMID 34052813.
2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 "Clinical pharmacology, efficacy, and safety of orexin receptor antagonists for the treatment of insomnia disorders". Expert Opin Drug Metab Toxicol 16 (11): 1063–1078. November 2020. doi:10.1080/17425255.2020.1817380. PMID 32901578.
3. ↑ 3.0 3.1 3.2 3.3 "Seltorexant - Janssen Research & Development/Minerva Neurosciences". AdisInsight. 2022-02-28. http://adisinsight.springer.com/drugs/800040115.
4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 "Hypocretins (orexins): The ultimate translational neuropeptides". J Intern Med 291 (5): 533–556. January 2022. doi:10.1111/joim.13406. PMID 35043499.
5. ↑ "Small-molecule antagonists of the orexin receptors". Pharmaceutical Patent Analyst 3 (6): 625–38. 2014. doi:10.4155/ppa.14.46. PMID 25489915.

## External links

* Seltorexant — AdisInsight

* v
* t
* e

Insomnia pharmacotherapies

GABAAR PAMs|

* Benzodiazepines: Brotizolam
* Cinolazepam
* Climazolam
* Clorazepate
* Doxefazepam
* Estazolam
* Etizolam
* Flunitrazepam
* Flurazepam
* Flutoprazepam
* Haloxazolam
* Loprazolam
* Lormetazepam
* Midazolam
* Nimetazepam
* Nitrazepam
* Quazepam
* Temazepam
* Triazolam; Nonbenzodiazepines/[[Chemistry:Z-drug|]] Eszopiclone
* Zaleplon
* Zolpidem
* Zopiclone; Others: Alcohols (e.g., ethchlorvynol, amylene hydrate, ethanol)
* Barbiturates (e.g., amobarbital, pentobarbital, phenobarbital, secobarbital)
* Bromides (e.g., potassium bromide, sodium bromide)
* Carbamates (e.g., meprobamate)
* Chloral hydrate
* Clomethiazole
* Kava
* Paraldehyde
* Piperidinediones (e.g., glutethimide)
* Quinazolinones (e.g., methaqualone)
* Sulfonmethane
* Valerian

Antihistamines
(H1R inverse agonists)|

* Alimemazine
* Captodiame
* Dimenhydrinate
* Diphenhydramine
* Doxylamine
* Etodroxizine
* Hydroxyzine
* Meclizine
* Methapyrilene
* Pheniramine
* Phenyltoloxamine
* Pimethixene
* Promethazine
* Propiomazine
* Pyrilamine
* TCAs (e.g., amitriptyline, doxepin, trimipramine)
* TeCAs (e.g., mirtazapine)
* Triprolidine

OXR antagonists|

* Almorexant§
* Filorexant§
* Lemborexant§
* Suvorexant

MTR agonists|

* Agomelatine
* Melatonin
* Ramelteon
* Tasimelteon

Miscellaneous|

* Antipsychotics (e.g., quetiapine, olanzapine, chlorpromazine)
* Ashwagandha
* Benzoctamine
* Cannabinoids (e.g., cannabis, dronabinol (THC), nabilone)
* Chamomile
* Fenadiazole
* Gabapentinoids (e.g., gabapentin, pregabalin, phenibut)
* Hops
* Lavender
* Menthyl isovalerate
* Niaprazine
* Opioids (e.g., hydrocodone, oxycodone, morphine)
* Passion flower
* Scopolamine
* Serotonin precursors (tryptophan, 5-HTP)
* Sodium oxybate (GHB)
* Sympatholytics (e.g., clonidine, guanfacine)
* TCAs (e.g., amitriptyline, doxepin, trimipramine)
* TeCAs (e.g., mirtazapine)
* Theanine
* Trazodone
* Valnoctamide

* v
* t
* e

Signaling peptide/protein receptor modulators

Adiponectin|

| AdipoR1|

* Agonists: Peptide: Adiponectin
* ADP-355
* ADP-399; Non-peptide: AdipoRon
* (–)-Arctigenin
* Arctiin
* Gramine
* Matairesinol

* Antagonists: Peptide: ADP-400

|

AdipoR2|

* Agonists: Peptide: Adiponectin
* ADP-355
* ADP-399; Non-peptide: AdipoRon
* Deoxyschizandrin
* Parthenolide
* Syringing
* Taxifoliol

* Antagonists: Peptide: ADP-400

Angiotensin|

* See here instead.

Bradykinin|

* Agonists: Bradykinin
* Kallidin

* Antagonists: FR-173657
* Icatibant
* LF22-0542

CGRP|

* Agonists: Amylin
* CGRP
* Pramlintide

* Antagonists: Atogepant
* BI 44370 TA
* CGRP (8-37)
* MK-3207
* Olcegepant
* Rimegepant
* SB-268262
* Telcagepant
* Ubrogepant

* Antibodies: Eptinezumab
* Erenumab
* Fremanezumab
* Galcanezumab

Cholecystokinin|

| CCKA|

* Agonists: Cholecystokinin

* Antagonists: Amiglumide
* Asperlicin
* Devazepide
* Dexloxiglumide
* Lintitript
* Lorglumide
* Loxiglumide
* Pranazepide
* Proglumide
* Tarazepide
* Tomoglumide

|

CCKB|

* Agonists: Cholecystokinin
* CCK-4
* Gastrin
* Pentagastrin (CCK-5)

* Antagonists: Ceclazepide
* CI-988 (PD-134308)
* Itriglumide
* L-365,360
* Netazepide
* Proglumide
* Spiroglumide

Unsorted|

* Antagonists: Nastorazepide

CRH|

| CRF1|

* Agonists: Cortagine
* Corticorelin
* Corticotropin releasing hormone
* Sauvagine
* Stressin I
* Urocortin

* Antagonists: Antalarmin
* Astressin-B
* CP-154,526
* Emicerfont
* Hypericin
* LWH-234
* NBI-27914
* NBI-74788
* Pexacerfont
* R-121919
* TS-041
* Verucerfont

|

CRF2|

* Agonists: Corticorelin
* Corticotropin releasing hormone
* Sauvagine
* Urocortin

* Antagonists: Astressin-B

Cytokine|

See here instead.

Endothelin|

* Agonists: Endothelin 1
* Endothelin 2
* Endothelin 3
* IRL-1620
* Sarafotoxin

* Antagonists: A-192621
* ACT-132577
* Ambrisentan
* Aprocitentan
* Atrasentan
* Avosentan
* Bosentan
* BQ-123
* BQ-788
* Clazosentan
* Darusentan
* Edonentan
* Enrasentan
* Fandosentan
* Feloprentan
* Macitentan
* Nebentan
* Sitaxentan
* Sparsentan
* Tezosentan
* Zibotentan

Galanin|

| GAL1|

* Agonists: Galanin
* Galanin (1-15)
* Galanin-like peptide
* Galmic
* Galnon
* NAX 810-2

* Antagonists: C7
* Dithiepine-1,1,4,4-tetroxide
* Galantide (M15)
* M32
* M35
* M40
* SCH-202596

|

GAL2|

* Agonists: Galanin
* Galanin (1-15)
* Galanin (2-11)
* Galanin-like peptide
* Galmic
* Galnon
* J18
* NAX 810-2

* Antagonists: C7
* Galantide (M15)
* M32
* M35
* M40
* M871

GAL3|

* Agonists: Galanin
* Galanin (1-15)
* Galmic
* Galnon

* Antagonists: C7
* Galantide (M15)
* GalR3ant
* HT-2157
* M32
* M35
* M40
* SNAP-37889
* SNAP-398299

Ghrelin/GHS|

* See here instead.

GH|

* See here instead.

GHRH|

* See here instead.

GLP|

| GLP-1|

* Agonists: Albiglutide
* Beinaglutide
* Dulaglutide
* Efpeglenatide
* Exenatide
* GLP-1
* Langlenatide
* Liraglutide
* Lixisenatide
* Oxyntomodulin
* Pegapamodutide
* Semaglutide
* Taspoglutide

|

GLP-2|

* Agonists: Apraglutide
* Elsiglutide
* Glepaglutide
* GLP-2
* Teduglutide

Others|

* Propeptides: Preproglucagon
* Proglucagon

Glucagon|

* Agonists: Dasiglucagon
* Glucagon
* Oxyntomodulin

* Antagonists: Adomeglivant
* L-168,049
* LGD-6972

* Propeptides: Preproglucagon
* Proglucagon

GnRH|

* See here instead.

Gonadotropin|

* See here instead.

Growth factor|

See here instead.

Insulin|

* Agonists: Chaetochromin (4548-G05)
* Insulin-like growth factor 1
* Insulin-like growth factor 2
* Insulin
* Insulin aspart
* Insulin degludec
* Insulin detemir
* Insulin glargine
* Insulin glulisine
* Insulin lispro
* Mecasermin
* Mecasermin rinfabate

* Antagonists: BMS-754807
* S661
* S961

* Kinase inhibitors: Linsitinib

* Antibodies: Xentuzumab (against IGF-1 and IGF-2)

Kisspeptin|

* Agonists: Kisspeptin
* Kisspeptin-10

* Antagonists: Kisspeptin-234

Leptin|

* Agonists: Leptin
* Metreleptin

MCH|

| MCH1|

* Agonists: Melanin concentrating hormone

* Antagonists: ATC-0065
* ATC-0175
* GW-803430
* NGD-4715
* SNAP-7941
* SNAP-94847

|

MCH2|

* Agonists: Melanin concentrating hormone

Melanocortin|

* See here instead.

Neuropeptide FF|

* Agonists: Neuropeptide AF
* Neuropeptide FF
* Neuropeptide SF (RFRP-1)
* Neuropeptide VF (RFRP-3)

* Antagonists: BIBP-3226
* RF9

Neuropeptide S|

* Agonists: Neuropeptide S

* Antagonists: ML-154
* SHA-68

Neuropeptide Y|

| Y1|

* Agonists: Neuropeptide Y
* Peptide YY

* Antagonists: BIBO-3304
* BIBP-3226
* BVD-10
* GR-231118
* PD-160170

|

Y2|

* Agonists: 2-Thiouridine 5'-triphosphate
* Neuropeptide Y
* Neuropeptide Y (13-36)
* Peptide YY
* Peptide YY (3-36)

* Antagonists: BIIE-0246
* JNJ-5207787
* SF-11

Y4|

* Agonists: GR-231118
* Neuropeptide Y
* Pancreatic polypeptide
* Peptide YY

* Antagonists: UR-AK49

Y5|

* Agonists: BWX-46
* Neuropeptide Y
* Peptide YY

* Antagonists: CGP-71683
* FMS-586
* L-152,804
* Lu AA-33810
* MK-0557
* NTNCB
* Velneperit (S-2367)

Neurotensin|

| NTS1|

* Agonists: Neurotensin
* Neuromedin N

* Antagonists: Meclinertant
* SR-142948

|

NTS2|

* Agonists: Neurotensin

* Antagonists: Levocabastine
* SR-142948

Opioid|

See here instead.

Orexin|

| OX1|

* Agonists: Orexin (A, B)

* Antagonists: ACT-335827
* ACT-462206
* Almorexant
* Filorexant
* Lemborexant
* Nemorexant
* RTIOX-276
* SB-334867
* SB-408124
* SB-649868
* Suvorexant
* TCS-1102

|

OX2|

* Agonists: Orexin (A, B)
* SB-668875

* Antagonists: ACT-335827
* ACT-462206
* Almorexant
* EMPA
* Filorexant
* JNJ-10397049
* Lemborexant
* MK-1064
* SB-649868
* Seltorexant
* Suvorexant
* TCS-1102
* TCS-OX2-29

Oxytocin|

* See here instead.

Prolactin|

* Agonists: Growth hormone
* Human placental lactogen
* Placental growth hormone (growth hormone variant)
* Prolactin
* S179D-hPRL
* Somatotropin

* Antagonists: Δ1–9-G129R-hPRL
* Δ1–14-G129R-hPRL
* G120K-hGH
* G129R-hPRL

* Prolactin modulators: Prolactin inhibitors: D2 receptor agonists (e.g., bromocriptine, cabergoline); Prolactin releasers: D2 receptor antagonists (e.g., domperidone, metoclopramide, risperidone)
* Estrogens (e.g., estradiol)
* Progestogens (e.g., progesterone)

PTH|

* Agonists: Abaloparatide
* Parathyroid hormone
* Parathyroid hormone-related protein (PTHrP)
* Semparatide
* Teriparatide

Relaxin|

* Agonists: Insulin-like factor 3
* Relaxin (1, 2, 3)
* Serelaxin

Somatostatin|

* See here instead.

Tachykinin|

* See here instead.

TRH|

* Agonists: Azetirelin
* Fertirelin
* Montirelin
* Orotirelin
* Posatirelin
* Protirelin
* Rovatirelin
* Taltirelin
* TRH (TRF)

TSH|

* Agonists: Thyrotropin alfa
* TSH (thyrotropin)

Vasopressin|

* See here instead.

VIP/PACAP|

| VIPR1|

* Agonists: Peptide: Bay 55-9837
* LBT-3393
* PACAP
* VIP

|

VIPR2|

* Agonists: Peptide: LBT-3627
* PACAP
* VIP

PAC1|

* Agonists: PACAP
* PACAP (1-27)
* PACAP (1-38)

* Antagonists: PACAP (6-38)

Unsorted|

* PHI
* PHM
* PHV

Others|

* Endogenous: Adrenomedullin
* Apelin
* Asprosin
* Bombesin
* Calcitonin
* Carnosine
* CART
* CLIP
* DSIP
* Enteroglucagon
* Formyl peptide
* GALP
* GIP
* GRP
* Integrin ligands (collagens, fibrinogen, fibronectin, laminins, ICAM-1, ICAM-2, osteopontin, VCAM-1, vitronectin)
* Kininogens
* Motilin
* Natriuretic peptides (ANP, BNP, CNP, urodilatin)
* Nesfatin-1
* Neuromedin B
* Neuromedin N
* Neuromedin S
* Neuromedin U
* Obestatin
* Osteocalcin
* Resistin
* Secretin
* Thymopoietin
* Thymosins
* Thymulin
* Urotensin-II
* VGF

* Exogenous: Lifitegrast (LFA-1 antagonist)

See also
Receptor/signaling modulators

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Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Seltorexant&oldid=871903"
*[US]: United States
*[CID]: Compound ID
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[GABAAR]: GABAA receptor
*[PAMs]: positive allosteric modulators
*[H1R]: H1 receptor
*[TCAs]: Tricyclic antidepressants
*[TeCAs]: Tetracyclic antidepressants
*[OXR]: Orexin receptor
*[MTR]: Melatonin receptor
*[THC]: tetrahydrocannabinol
*[5-HTP]: 5-hydroxytryptophan
*[GHB]: γ-aminobutyric acid