Ritanserin

Ritanserin
Clinical data
Other namesR-55667; R55667; Tiserton
ATC code
  • None
Identifiers
  • 6-[2-[4-[bis(4-fluorophenyl)methylidene]piperidin-1-yl]ethyl]-7-methyl-[1,3]thiazolo[2,3-b]pyrimidin-5-one
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.163.772 Edit this at Wikidata
Chemical and physical data
FormulaC27H25F2N3OS
Molar mass477.57 g·mol−1
3D model (JSmol)
  • CC1=C(C(=O)N2C=CSC2=N1)CCN3CCC(=C(C4=CC=C(C=C4)F)C5=CC=C(C=C5)F)CC3
  • InChI=1S/C27H25F2N3OS/c1-18-24(26(33)32-16-17-34-27(32)30-18)12-15-31-13-10-21(11-14-31)25(19-2-6-22(28)7-3-19)20-4-8-23(29)9-5-20/h2-9,16-17H,10-15H2,1H3 ☒N
  • Key:JUQLTPCYUFPYKE-UHFFFAOYSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Ritanserin, also known by its developmental code name R-55667, is a serotonin antagonist medication described as an anxiolytic, antidepressant, antiparkinsonian agent, and antihypertensive agent.[1][2][3] It was chiefly investigated as a drug to treat insomnia, especially to enhance sleep quality by significantly increasing slow wave sleep by virtue of potent and concomitant 5HT2a and 5HT2c antagonism[4][5]

It was never marketed for medical use due to safety problems but is currently used in scientific research.

Some of the safety liabilities that lead to its discontinuation for the treatment of insomnia has led to its potential repurposing in the field of oncology. Specifically, ritanserin acts as a potent inhibitor of diacylglycerol kinase alpha (DGKα). As such, it may be used to treat certain types of glioblastoma[6][7] and melanoma. It has also been used as a reference compound to identify putatively more selective and potent DGKα inhibitors to treat these forms of cancer as well as possibly others.[8]

Additionally, ritanserin blocks c-RAF activation and induces apoptotic cell death of non–small cell lung cancer and small cell lung cancer cells.[9]

  1. ^ Cite error: The named reference Elks2014 was invoked but never defined (see the help page).
  2. ^ Morton I, Morton IK, Hall JM (31 October 1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 249–. ISBN 978-0-7514-0499-9.
  3. ^ Alpert JE, Fava M, Alpert JE, eds. (14 May 2014). Handbook of Chronic Depression: Diagnosis and Therapeutic Management. CRC Press. pp. 117–. ISBN 978-0-8247-5660-4.
  4. ^ Paiva T, Arriaga F, Wauquier A, Lara E, Largo R, Leitao JN (1988). "Effects of ritanserin on sleep disturbances of dysthymic patients". Psychopharmacology. 96 (3): 395–9. doi:10.1007/BF00216069. PMID 3146774. S2CID 19232592.
  5. ^ Idzikowski C, Mills FJ, Glennard R (July 1986). "5-Hydroxytryptamine-2 antagonist increases human slow wave sleep". Brain Research. 378 (1): 164–8. doi:10.1016/0006-8993(86)90299-4. PMID 3091188. S2CID 43604995.
  6. ^ Olmez I, Love S, Xiao A, Manigat L, Randolph P, McKenna BD, et al. (January 2018). "Targeting the mesenchymal subtype in glioblastoma and other cancers via inhibition of diacylglycerol kinase alpha". Neuro-Oncology. 20 (2): 192–202. doi:10.1093/neuonc/nox119. PMC 5777487. PMID 29048560.
  7. ^ Audia A, Bhat KP (January 2018). "Ritanserin, a novel agent targeting the mesenchymal subtype of glioblastomas". Neuro-Oncology. 20 (2): 151–152. doi:10.1093/neuonc/nox240. PMC 5786216. PMID 29365204.
  8. ^ Granade ME, Manigat LC, Lemke MC, Purow BW, Harris TE (March 2022). "Identification of ritanserin analogs that display DGK isoform specificity". Biochemical Pharmacology. 197: 114908. doi:10.1016/j.bcp.2022.114908. PMC 8858877. PMID 34999054.
  9. ^ Campbell ST, Franks CE, Borne AL, Shin M, Zhang L, Hsu KL (November 2018). "Chemoproteomic Discovery of a Ritanserin-Targeted Kinase Network Mediating Apoptotic Cell Death of Lung Tumor Cells". Molecular Pharmacology. 94 (5): 1246–1255. doi:10.1124/mol.118.113001. PMC 6160665. PMID 30158316.