TAK-994

TAK-994 is an orexin receptor agonist which is under development by Takeda for the treatment of narcolepsy.[2][3] It is a small-molecule and orally active compound and acts as a highly selective agonist of the orexin receptor 2 (OX2) (>700-fold selectivity over the orexin receptor 1 (OX1)).[2][3][4][1] TAK-994 is related to danavorexton (TAK-925).[5] The compound reached phase 2 clinical trials for narcolepsy.[6] However, clinical development was discontinued in October 2021 for safety reasons.[5][7][8][9][10] The chemical structure of TAK-994 has yet to be disclosed.[4]

TAK-994
Clinical data
Routes of
administration		Oral[1]
Drug classOrexin receptor agonist

See also

References
  1. 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.
  2. Ishikawa 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–A56. doi:10.1093/sleep/zsaa056.139. eISSN 1550-9109. ISSN 0161-8105.
  3. Thorpy 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.
  4. 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. PMID 34101446.
  5. Jacobson LH, Hoyer D, de Lecea L (January 2022). "Hypocretins (orexins): The ultimate translational neuropeptides". J Intern Med. doi:10.1111/joim.13406. PMID 35043499.
  6. Clinical trial number NCT04096560 for "A Study of TAK-994 in Adults With Type 1 and Type 2 Narcolepsy" at ClinicalTrials.gov
  7. "Takeda Provides Update on TAK-994 Clinical Program". Business Wire. 5 October 2021.
  8. "Takeda pauses TAK-994 clinical studies due to safety glitch". The Pharma Letter. 6 October 2021.
  9. Jackson M (6 October 2021). "Takeda Halts Phase II Studies For Key R&D Asset TAK-994 In Narcolepsy". Scrip. Informa Pharma Intelligence.
  10. Tong A (6 October 2021). "Takeda flashes red light on 'breakthrough' narcolepsy drug after PhII trials turned up mysterious safety signal". Endpoints News.



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