Fezolinetant
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MedKoo CAT#: 327010

CAS#: 1629229-37-3 (free base)

Description: Fezolinetant, also known as ESN-364, is Neurokinin-3 (NK-3) receptor antagonist which has been optimized for use in women’s health, and is being developed for sex-hormone related disorders such as endometriosis, polycystic ovarian syndrome and uterine fibroids. Fexolinetant allows modulation of the hypothalamic-pituitary gonadal axis with a selective action on hormones relevant to disease. The agent is expected to have greater tolerability than competing products which target GnRH (Gonadotropin-releasing hormone).


Chemical Structure

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Fezolinetant
CAS# 1629229-37-3 (free base)

Theoretical Analysis

MedKoo Cat#: 327010
Name: Fezolinetant
CAS#: 1629229-37-3 (free base)
Chemical Formula: C16H15FN6OS
Exact Mass: 358.1012
Molecular Weight: 358.4
Elemental Analysis: C, 53.62; H, 4.22; F, 5.30; N, 23.45; O, 4.46; S, 8.95

Price and Availability

Size Price Availability Quantity
5.0mg USD 145.0 Ready to ship
10.0mg USD 250.0 Ready to ship
25.0mg USD 550.0 Ready to ship
50.0mg USD 950.0 Ready to ship
100.0mg USD 1450.0 Ready to ship
200.0mg USD 2450.0 Ready to ship
500.0mg USD 3450.0 Ready to ship
1.0g USD 4650.0 2 Weeks
2.0g USD 6950.0 2 Weeks
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Related CAS #: 929016-98-8 (HCl)   1629229-37-3 (free base)  

Synonym: Fezolinetant; ESN-364; ESN 364; ESN364

IUPAC/Chemical Name: (R)-(4-fluorophenyl)(8-methyl-3-(3-methyl-1,2,4-thiadiazol-5-yl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methanone

InChi Key: PPSNFPASKFYPMN-SECBINFHSA-N

InChi Code: InChI=1S/C16H15FN6OS/c1-9-13-19-20-14(15-18-10(2)21-25-15)23(13)8-7-22(9)16(24)11-3-5-12(17)6-4-11/h3-6,9H,7-8H2,1-2H3/t9-/m1/s1

SMILES Code: O=C(C1=CC=C(F)C=C1)N2[C@H](C)C3=NN=C(C4=NC(C)=NS4)N3CC2

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Fezolinetant is an antagonist of the neurokinin 3 receptor (NK3R).
In vivo activity: Repeated oral administration of fezolinetant (1-10 mg/kg, twice daily) for 1 week dose-dependently reduced plasma LH levels without affecting estradiol or FSH levels, inhibited the activation of MnPO neurons, and attenuated hot flash-like symptoms. In addition, fezolinetant dose-dependently reduced hyperphagia and weight gain in ovariectomized rats. These preclinical findings suggest that fezolinetant attenuates hot flash-like symptoms via inhibition of neuronal activity in the MnPO of ovariectomized rats and provides further support for the ongoing clinical development of fezolinetant for the treatment of VMS associated with menopause. Reference: Eur J Pharmacol. 2021 Aug 15;905:174207. https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(21)00360-5

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 20.0 55.8

Preparing Stock Solutions

The following data is based on the product molecular weight 358.4 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
In vivo protocol: 1. Tahara A, Takamatsu H, Ohtake A, Tanaka-Amino K, Kaku S. Effects of neurokinin 3 receptor antagonist fezolinetant on hot flash-like symptoms in ovariectomized rats. Eur J Pharmacol. 2021 Aug 15;905:174207. doi: 10.1016/j.ejphar.2021.174207. Epub 2021 May 25. PMID: 34048742.

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1: Menown SJ, Tello JA. Neurokinin 3 Receptor Antagonists Compared With Serotonin Norepinephrine Reuptake Inhibitors for Non-Hormonal Treatment of Menopausal Hot Flushes: A Systematic Qualitative Review. Adv Ther. 2021 Oct;38(10):5025-5045. doi: 10.1007/s12325-021-01900-w. Epub 2021 Sep 12. PMID: 34514552; PMCID: PMC8478773.

2: Tahara A, Takamatsu H, Ohtake A, Tanaka-Amino K, Kaku S. Effects of neurokinin 3 receptor antagonist fezolinetant on hot flash-like symptoms in ovariectomized rats. Eur J Pharmacol. 2021 Aug 15;905:174207. doi: 10.1016/j.ejphar.2021.174207. Epub 2021 May 25. PMID: 34048742.

3: Fraser GL, Obermayer-Pietsch B, Laven J, Griesinger G, Pintiaux A, Timmerman D, Fauser BCJM, Lademacher C, Combalbert J, Hoveyda HR, Ramael S. Randomized Controlled Trial of Neurokinin 3 Receptor Antagonist Fezolinetant for Treatment of Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2021 Aug 18;106(9):e3519-e3532. doi: 10.1210/clinem/dgab320. PMID: 34000049; PMCID: PMC8372662.

4: Depypere H, Lademacher C, Siddiqui E, Fraser GL. Fezolinetant in the treatment of vasomotor symptoms associated with menopause. Expert Opin Investig Drugs. 2021 Jul;30(7):681-694. doi: 10.1080/13543784.2021.1893305. Epub 2021 Jul 12. PMID: 33724119.

5: Carpenter JS. Fezolinetant findings can fuel future instrumentation inquiries. Menopause. 2020 Dec;27(12):1347. doi: 10.1097/GME.0000000000001648. PMID: 33048862.

6: Santoro N, Waldbaum A, Lederman S, Kroll R, Fraser GL, Lademacher C, Skillern L, Young J, Ramael S. Effect of the neurokinin 3 receptor antagonist fezolinetant on patient-reported outcomes in postmenopausal women with vasomotor symptoms: results of a randomized, placebo-controlled, double-blind, dose- ranging study (VESTA). Menopause. 2020 Dec;27(12):1350-1356. doi: 10.1097/GME.0000000000001621. PMID: 32769757; PMCID: PMC7709922.

7: Reame NK. More promising news (mostly) on manipulating neurokinin B activity as a nonhormonal treatment of hot flashes. Menopause. 2020 Apr;27(4):375-376. doi: 10.1097/GME.0000000000001530. PMID: 32132443.

8: Fraser GL, Lederman S, Waldbaum A, Kroll R, Santoro N, Lee M, Skillern L, Ramael S. A phase 2b, randomized, placebo-controlled, double-blind, dose-ranging study of the neurokinin 3 receptor antagonist fezolinetant for vasomotor symptoms associated with menopause. Menopause. 2020 Apr;27(4):382-392. doi: 10.1097/GME.0000000000001510. PMID: 32102086; PMCID: PMC7147405.

9: Depypere H, Timmerman D, Donders G, Sieprath P, Ramael S, Combalbert J, Hoveyda HR, Fraser GL. Treatment of Menopausal Vasomotor Symptoms With Fezolinetant, a Neurokinin 3 Receptor Antagonist: A Phase 2a Trial. J Clin Endocrinol Metab. 2019 Dec 1;104(12):5893-5905. doi: 10.1210/jc.2019-00677. PMID: 31415087.

10: Yamamoto K, Inuki S, Ohno H, Oishi S. Scaffold hopping of fused piperidine- type NK3 receptor antagonists to reduce environmental impact. Bioorg Med Chem. 2019 May 15;27(10):2019-2026. doi: 10.1016/j.bmc.2019.03.059. Epub 2019 Apr 1. PMID: 30975505.

11: Skorupskaite K, George JT, Veldhuis JD, Millar RP, Anderson RA. Neurokinin 3 receptor antagonism decreases gonadotropin and testosterone secretion in healthy men. Clin Endocrinol (Oxf). 2017 Dec;87(6):748-756. doi: 10.1111/cen.13445. Epub 2017 Sep 5. PMID: 28802064.

12: Cully M. Deal watch: Neurokinin 3 receptor antagonist revival heats up with Astellas acquisition. Nat Rev Drug Discov. 2017 May 31;16(6):377. doi: 10.1038/nrd.2017.102. PMID: 28559557.

13: Fraser GL, Ramael S, Hoveyda HR, Gheyle L, Combalbert J. The NK3 Receptor Antagonist ESN364 Suppresses Sex Hormones in Men and Women. J Clin Endocrinol Metab. 2016 Feb;101(2):417-26. doi: 10.1210/jc.2015-3621. Epub 2015 Dec 14. PMID: 26653113.