Movatterモバイル変換

[0]ホーム
URL:

Jump to content
WikipediaThe Free Encyclopedia
Search

Firazorexton

From Wikipedia, the free encyclopedia
Chemical compound

Pharmaceutical compound
Firazorexton
Clinical data
Other namesTAK-994
Identifiers
  • N-[(2S,3S)-2-[[3-(3,5-difluorophenyl)-2-fluorophenyl]methyl]-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]methanesulfonamide
CAS Number
PubChemCID
ChemSpider
UNII
Chemical and physical data
FormulaC22H25F3N2O4S
Molar mass470.51 g·mol−1
3D model (JSmol)
  • CC(C)(C(=O)N1CC[C@@H]([C@@H]1CC2=C(C(=CC=C2)C3=CC(=CC(=C3)F)F)F)NS(=O)(=O)C)O
  • InChI=1S/C22H25F3N2O4S/c1-22(2,29)21(28)27-8-7-18(26-32(3,30)31)19(27)11-13-5-4-6-17(20(13)25)14-9-15(23)12-16(24)10-14/h4-6,9-10,12,18-19,26,29H,7-8,11H2,1-3H3/t18-,19-/m0/s1
  • Key:VOSAWOSMGPKQEQ-OALUTQOASA-N

Firazorexton (INNTooltip International Nonproprietary Name; development codeTAK-994) is anexperimentalorexin 2 (OX2) receptoragonist first described in a 2019patent filed byTakeda Pharmaceutical Company.[1][2]

Firazorexton was studied byTakeda for the treatment ofnarcolepsy.[3][4][5] It is asmall-molecule andorally activecompound and acts as a highlyselectiveagonist of theorexin receptor 2 (OX2) with >700-fold selectivity over theorexin receptor 1 (OX1).[3][4][6][7] Firazorexton is related todanavorexton (TAK-925).[8]

The compound reachedphase 2clinical trials for narcolepsy.[9] However, clinical development was discontinued in October 2021 forsafety reasons.[8][10][11][12][13] More specifically, it produced severedrug-induced liver injury in phase 2 trials.[14] Thishepatotoxicity is unlikely to be related to firazorexton's orexin receptor agonism.[14]

See also

[edit]

References

[edit]
  1. ^"International Nonproprietary Names for Pharmaceutical Substances (INN)"(PDF).WHO Drug Information.34 (1):93–269. 2020.Proposed INN: List 123
  2. ^WO application 2019027058, Kajita Y, Mikami S, Miyanohana Y, Koike T, Daini M, Oyabu N, Ogino M, Takeuchi K, Ito Y, Tokunaga N, Sugimoto T, Miyazaki T, Oda T, Hoashi Y, Hattori Y, Imamura K, "Heterocyclic compound and use therof", published 2019-02-07, assigned toTakeda Pharmaceutical Company 
  3. ^abIshikawa T, Suzuki M, Kimura H (April 2020)."0141 A Novel, Orally Available Orexin 2 Receptor-Selective Agonist, TAK-994, Shows Wake-Promoting Effects Following Chronic Dosing in an Orexin-Deficient Narcolepsy Mouse Model".Sleep.43 (Supplement 1): A56.doi:10.1093/sleep/zsaa056.139.eISSN 1550-9109.ISSN 0161-8105.
  4. ^abThorpy MJ (January 2020)."Recently Approved and Upcoming Treatments for Narcolepsy".CNS Drugs.34 (1):9–27.doi:10.1007/s40263-019-00689-1.PMC 6982634.PMID 31953791.
  5. ^Ishikawa T, Hara H, Kawano A, Tohyama K, Kajita Y, Miyanohana Y, et al. (June 2023)."TAK-994, a Novel Orally Available Brain-Penetrant Orexin 2 Receptor-Selective Agonist, Suppresses Fragmentation of Wakefulness and Cataplexy-Like Episodes in Mouse Models of Narcolepsy".The Journal of Pharmacology and Experimental Therapeutics.385 (3):193–204.doi:10.1124/jpet.122.001449.PMID 37001988.S2CID 257879743.
  6. ^Zhang D, Perrey DA, Decker AM, Langston TL, Mavanji V, Harris DL, et al. (June 2021)."Discovery of Arylsulfonamides as Dual Orexin Receptor Agonists".Journal of Medicinal Chemistry.64 (12):8806–8825.doi:10.1021/acs.jmedchem.1c00841.PMC 8994207.PMID 34101446.
  7. ^Pellitteri G, de Biase S, Valente M, Gigli GL (August 2021). "How treatable is narcolepsy with current pharmacotherapy and what does the future hold?".Expert Opinion on Pharmacotherapy.22 (12):1517–1520.doi:10.1080/14656566.2021.1915987.PMID 33882765.S2CID 233349300.
  8. ^abJacobson LH, Hoyer D, de Lecea L (May 2022). "Hypocretins (orexins): The ultimate translational neuropeptides".Journal of Internal Medicine.291 (5):533–556.doi:10.1111/joim.13406.PMID 35043499.S2CID 248119793.
  9. ^Clinical trial numberNCT04096560 for "A Study of TAK-994 in Adults With Type 1 and Type 2 Narcolepsy" atClinicalTrials.gov
  10. ^"Takeda Provides Update on TAK-994 Clinical Program".Business Wire. 5 October 2021.
  11. ^"Takeda pauses TAK-994 clinical studies due to safety glitch".The Pharma Letter. 6 October 2021.
  12. ^Jackson M (6 October 2021)."Takeda Halts Phase II Studies For Key R&D Asset TAK-994 In Narcolepsy".Scrip. Informa Pharma Intelligence.
  13. ^Tong A (6 October 2021)."Takeda flashes red light on 'breakthrough' narcolepsy drug after PhII trials turned up mysterious safety signal".Endpoints News.
  14. ^abShinozawa T, Miyamoto K, Baker KS, Faber SC, Flores R, Uetrecht J, et al. (April 2025)."TAK-994 mechanistic investigation into drug-induced liver injury".Toxicological Sciences.204 (2):143–153.doi:10.1093/toxsci/kfaf003.PMC 11939078.PMID 39786842.
Catecholaminergic agents
  • Serotonin–norepinephrine–dopamine reuptake inhibitors (SNDRIs):Mazindol
Orexin receptor agonists
Histamine H3 receptor antagonists
Adenosine receptor antagonists
Others
OX1
OX2
Retrieved from "https://en.wikipedia.org/w/index.php?title=Firazorexton&oldid=1315535574"
Categories:
Hidden categories:
[8]ページ先頭
©2009-2025 Movatter.jp