Zuranolone

Zuranolone (INN;[3] developmental code names SAGE-217, S-812217) is an investigational medication which is under development by SAGE Therapeutics for the treatment of depressive disorders and a variety of other indications.[4][5] It is a synthetic, orally active, inhibitory pregnane neurosteroid, and acts as a positive allosteric modulator of the GABAA receptor.[4][5][6] The drug was developed as an improvement of brexanolone (allopregnanolone) with high oral bioavailability and a biological half-life suitable for once-daily administration.[5] Its half-life is around 16 to 23 hours, compared to approximately 9 hours for brexanolone.[1][2] As of March 2022, zuranolone is in phase III clinical trials for major depressive disorder, postpartum depression, and insomnia and is in phase II clinical studies for bipolar depression, essential tremor, and Parkinson's disease.[4] It is also in the preclinical stage of development for dyskinesias.[4]

Zuranolone
Clinical data
Other namesSAGE-217; S-812217; SGE-797; BIIB-125; 3α-Hydroxy-3β-methyl-21-(4-cyano-1H-pyrazol-1'-yl)-19-nor-5β-pregnan-20-one; 3β-Methyl-21-(4-cyano-1H-pyrazol-1'-yl)-19-norpregnanolone; 3α-Hydroxy-3β-methyl-5β-dihydro-21-(4-cyano-1H-pyrazol-1'-yl)-19-norprogesterone
Routes of
administration		By mouth
Drug classNeurosteroid; GABAA receptor positive allosteric modulator
Pharmacokinetic data
Elimination half-life16–23 hours[1][2]
Identifiers
IUPAC name
  • 1-(2-((3R,5R,8R,9R,10S,13S,14S,17S)-3-Hydroxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-1H-pyrazole-4-carbonitrile
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
Chemical and physical data
FormulaC25H35N3O2
Molar mass409.574 g·mol−1
3D model (JSmol)
SMILES
  • O=C(CN1N=CC(C#N)=C1)[C@H]2CC[C@@]3([H])[C@]4([H])CC[C@]5([H])C[C@](C)(O)CC[C@]5([H])[C@@]4([H])CC[C@@]32C
InChI
  • InChI=1S/C25H35N3O2/c1-24(30)9-7-18-17(11-24)3-4-20-19(18)8-10-25(2)21(20)5-6-22(25)23(29)15-28-14-16(12-26)13-27-28/h13-14,17-22,30H,3-11,15H2,1-2H3/t17-,18+,19-,20-,21+,22-,24-,25+/m1/s1
  • Key:HARRKNSQXBRBGZ-GVKWWOCJSA-N

See also

References
  1. Cerne R, Lippa A, Poe MM, Smith JL, Jin X, Ping X, Golani LK, Cook JM, Witkin JM (June 2022). "GABAkines - Advances in the discovery, development, and commercialization of positive allosteric modulators of GABAA receptors". Pharmacol Ther. 234: 108035. doi:10.1016/j.pharmthera.2021.108035. PMID 34793859.
  2. Faden J, Citrome L (2020). "Intravenous brexanolone for postpartum depression: what it is, how well does it work, and will it be used?". Ther Adv Psychopharmacol. 10: 2045125320968658. doi:10.1177/2045125320968658. PMC 7656877. PMID 33224470.
  3. "International Nonproprietary Names for Pharmaceutical Substances" (PDF). WHO Drug Information. 32 (4). 2018.
  4. "SAGE 217". AdisInsight. Retrieved 2018-02-10.
  5. Blanco MJ, La D, Coughlin Q, Newman CA, Griffin AM, Harrison BL, Salituro FG (2018). "Breakthroughs in neuroactive steroid drug discovery". Bioorg. Med. Chem. Lett. 28 (2): 61–70. doi:10.1016/j.bmcl.2017.11.043. PMID 29223589.
  6. Martinez Botella G, Salituro FG, Harrison BL, Beresis RT, Bai Z, Blanco MJ, Belfort GM, Dai J, Loya CM, Ackley MA, Althaus AL, Grossman SJ, Hoffmann E, Doherty JJ, Robichaud AJ (2017). "Neuroactive Steroids. 2. 3α-Hydroxy-3β-methyl-21-(4-cyano-1H-pyrazol-1'-yl)-19-nor-5β-pregnan-20-one (SAGE-217): A Clinical Next Generation Neuroactive Steroid Positive Allosteric Modulator of the (γ-Aminobutyric Acid)A Receptor". J. Med. Chem. 60 (18): 7810–7819. doi:10.1021/acs.jmedchem.7b00846. PMID 28753313.
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