Danavorexton

Danavorexton
Clinical data
Other names	TAK-925
Routes of; administration	Intravenous
Drug class	Orexin receptor agonist; Orexin OX2 receptor agonist; Wakefulness-promoting agent
Pharmacokinetic data
Elimination half-life	~3.3–5.1 hours
Identifiers
	IUPAC name methyl (2R,3S)-3-(methanesulfonamido)-2-[(cis-4-phenylcyclohexyl)oxymethyl]piperidine-1-carboxylate;
CAS Number	2114324-48-8;
PubChem CID	130310079;
ChemSpider	68011464;
UNII	1QMD83K4YN;
ChEMBL	ChEMBL4650341;
PDB ligand	A6F (PDBe, RCSB PDB);
CompTox Dashboard (EPA)	DTXSID401336757 ;
Chemical and physical data
Formula	C21H32N2O5S
Molar mass	424.56 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES COC(=O)N1CCC[C@H](NS(C)(=O)=O)[C@@H]1CO[C@H]1CC[C@H](CC1)C1=CC=CC=C1;
	InChI InChI=1S/C21H32N2O5S/c1-27-21(24)23-14-6-9-19(22-29(2,25)26)20(23)15-28-18-12-10-17(11-13-18)16-7-4-3-5-8-16/h3-5,7-8,17-20,22H,6,9-15H2,1-2H3/t17-,18+,19-,20-/m0/s1; Key:UXZAJSZFFARTEI-YRPNKDGESA-N;

Danavorexton (developmental code name TAK-925) is a selective orexin 2 receptor agonist.^[1] It is a small-molecule compound and is administered intravenously.^[1]^[2] The compound was found to dose-dependently produce wakefulness to a similar degree as modafinil in a phase 1 clinical trial.^[1]^[4] As of March 2021, danavorexton is under development for the treatment of narcolepsy, idiopathic hypersomnia, and sleep apnea.^[2]^[1]^[5] It is related to another orexin receptor agonist, firazorexton (TAK-994), the development of which was discontinued for safety reasons in October 2021.^[1]^[6]

References

1 2 3 4 5 6 Jacobson LH, Hoyer D, de Lecea L (January 2022). "Hypocretins (orexins): The ultimate translational neuropeptides". J Intern Med. 291 (5): 533–556. doi:10.1111/joim.13406. PMID 35043499. S2CID 248119793.
1 2 3 "Danavorexton - Takeda". Adis Insight. Springer Nature Switzerland AG. Retrieved 7 March 2021.
↑ Evans R, Kimura H, Alexander R, Davies CH, Faessel H, Hartman DS, Ishikawa T, Ratti E, Shimizu K, Suzuki M, Tanaka S, Yukitake H, Dauvilliers Y, Mignot E (August 2022). "Orexin 2 receptor-selective agonist danavorexton improves narcolepsy phenotype in a mouse model and in human patients". Proc Natl Acad Sci U S A. 119 (35) e2207531119. doi:10.1073/pnas.2207531119. PMC 9436334. PMID 35994639.
↑ Evans, R., Hazel, J., Faessel, H., Wu, J., Hang, Y., Alexander, R., ... & Hartman, D. (2019). Results of a phase 1, 4-period crossover, placebo-controlled, randomized, single dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-925, a novel orexin 2 receptor agonist, in sleep-deprived healthy adults, utilizing modafinil as an active comparator. Sleep Medicine, 64, S106. https://scholar.google.com/scholar?cluster=10933819770107034612
↑ Evans R, Tanaka S, Tanaka S, Touno S, Shimizu K, Sakui S, et al. (December 2019). "A Phase 1 single ascending dose study of a novel orexin 2 receptor agonist, TAK-925, in healthy volunteers (HV) and subjects with narcolepsy type 1 (NT1) to assess safety, tolerability, pharmacokinetics, and pharmacodynamic outcomes". Sleep Medicine. 64: S105–S106. doi:10.1016/j.sleep.2019.11.290. S2CID 213696542.
↑ Tong A (6 October 2021). "Takeda flashes red light on 'breakthrough' narcolepsy drug after PhII trials turned up mysterious safety signal". Endpoints News.

External links

Danavorexton - AdisInsight

This drug article relating to the nervous system is a stub. You can help Wikipedia by adding missing information.

[pmid35043499-1] 1 2 3 4 5 6 Jacobson LH, Hoyer D, de Lecea L (January 2022). "Hypocretins (orexins): The ultimate translational neuropeptides". J Intern Med. 291 (5): 533–556. doi:10.1111/joim.13406. PMID 35043499. S2CID 248119793.

[AdisInsight-2] 1 2 3 "Danavorexton - Takeda". Adis Insight. Springer Nature Switzerland AG. Retrieved 7 March 2021.

[EvansKimuraAlexander2022-3] Evans R, Kimura H, Alexander R, Davies CH, Faessel H, Hartman DS, Ishikawa T, Ratti E, Shimizu K, Suzuki M, Tanaka S, Yukitake H, Dauvilliers Y, Mignot E (August 2022). "Orexin 2 receptor-selective agonist danavorexton improves narcolepsy phenotype in a mouse model and in human patients". Proc Natl Acad Sci U S A. 119 (35) e2207531119. doi:10.1073/pnas.2207531119. PMC 9436334. PMID 35994639.

[EvansHazel2019-4] Evans, R., Hazel, J., Faessel, H., Wu, J., Hang, Y., Alexander, R., ... & Hartman, D. (2019). Results of a phase 1, 4-period crossover, placebo-controlled, randomized, single dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-925, a novel orexin 2 receptor agonist, in sleep-deprived healthy adults, utilizing modafinil as an active comparator. Sleep Medicine, 64, S106. https://scholar.google.com/scholar?cluster=10933819770107034612

[5] Evans R, Tanaka S, Tanaka S, Touno S, Shimizu K, Sakui S, et al. (December 2019). "A Phase 1 single ascending dose study of a novel orexin 2 receptor agonist, TAK-925, in healthy volunteers (HV) and subjects with narcolepsy type 1 (NT1) to assess safety, tolerability, pharmacokinetics, and pharmacodynamic outcomes". Sleep Medicine. 64: S105–S106. doi:10.1016/j.sleep.2019.11.290. S2CID 213696542.

[EndpointNews2021-6] Tong A (6 October 2021). "Takeda flashes red light on 'breakthrough' narcolepsy drug after PhII trials turned up mysterious safety signal". Endpoints News.

[1]

[2]

[3]

[4]

[5]

[6]

v t e Wakefulness-promoting agents
Catecholaminergic agents	Dopamine reuptake inhibitors (DRIs): Adrafinil^‡ Armodafinil Esmodafinil Mesocarb^‡ Modafinil Phenylpiracetam (fonturacetam) Norepinephrine reuptake inhibitors (NRIs): Atomoxetine Desipramine Reboxetine Viloxazine Norepinephrine–dopamine reuptake inhibitors (NDRIs): Amineptine^‡ Bupropion Dexmethylphenidate Methylphenidate Nomifensine^‡ Serdexmethylphenidate Solriamfetol Serotonin–norepinephrine–dopamine reuptake inhibitors (SNDRIs): Mazindol Norepinephrine releasing agents (NRAs): Ephedrine Pseudoephedrine Selegiline (via metabolites) Norepinephrine–dopamine releasing agents (NDRAs): Amphetamine Dextroamphetamine Levoamphetamine^‡ Lisdexamfetamine Methamphetamine Mixed amphetamine salts Pemoline^‡
Orexin receptor agonists	Alixorexton^§ Balumorexton^§ Cleminorexton^§ Danavorexton^§ Firazorexton^§ Ledasorexton^§ Oveporexton^†
Histamine H₃ receptor antagonists	Pitolisant Samelisant^§
Adenosine receptor antagonists	Caffeine Istradefylline Paraxanthine
Others	GABA_A receptor antagonists and negative allosteric modulators (e.g., clarithromycin, flumazenil, pentylenetetrazol (pentetrazol)) GABA_B receptor agonists (e.g., sodium oxybate/γ-hydroxybutyrate (GHB)) (via improved nightly sleep) Nicotinic acetylcholine receptor agonists (e.g., nicotine)
^#WHO-EM ^‡Withdrawn from market Clinical trials: ^†Phase III ^§Never to phase III
See also: Stimulants List of investigational narcolepsy and hypersomnia drugs

See also

References

External links