Cipepofol

Cipepofol
Clinical data
Trade namesCypsedo
Other namesCiprofol; CS-0064163; CS0064163; GTPL10812; GTPL-10812; HSK-3486; HSK3486; HY-116152; HY116152; (R)-2-(1-Cyclopropylethyl)-6-isopropylphenol
AHFS/Drugs.comcypsedo
License data
Routes of
administration		Intravenous infusion
Drug classGABAA receptor positive allosteric modulator
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
MetabolismLiver glucuronidation
ExcretionKidney
Identifiers
  • 2-[(1R)-1-cyclopropylethyl]-6-propan-2-ylphenol
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC14H20O
Molar mass204.313 g·mol−1
3D model (JSmol)
  • C[C@H](C1CC1)C2=CC=CC(=C2O)C(C)C
  • InChI=1S/C14H20O/c1-9(2)12-5-4-6-13(14(12)15)10(3)11-7-8-11/h4-6,9-11,15H,7-8H2,1-3H3/t10-/m1/s1
  • Key:BMEARIQHWSVDBS-SNVBAGLBSA-N

Cipepofol (INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name), also known as ciprofol or by its developmental code name HSK3486, sold under the brand name Cypsedo, is a general anesthetic related to propofol which is used for anesthesia and sedation. The drug is used by intravenous infusion. A short-acting and highly selective GABAA positive allosteric modulator, ciprofol is 4 to 6 times more potent than other phenol derivatives such as propofol or fospropofol.

In May 2026, cipepofol was approved for medical use in the United States. Manufactured by Haisco Pharmaceutical Group, ciprofol underwent phase I and II trials in Australia and China.

Physical properties

Ciprofol is an optically active 2,6-disubstituted alkylphenol with a cyclopropylethyl group incorporated at the second carbon atom. This cyclopropyl group increases the steric effects and introduces stereoselective effects over its anesthetic properties. These properties appear to increase the anesthetic potency of ciprofol, when compared with propofol.

Medical uses

Ciprofol is used for the intravenous induction of general anesthesia. Studies published in 2022 and 2023 found it was efficacious as a general anesthetic in people undergoing gynecological surgery and kidney transplantation, as well as for endoscopic procedures such as bronchoscopy, esophagogastroduodenoscopy and colonoscopy.

Ciprofol has also been used for sedation of critically ill people undergoing mechanical ventilation in the intensive care unit, as well as for the treatment of agitation and delirium in that patient population. When combined with mild therapeutic hypothermia, ciprofol may also be useful as a cerebral protective agent in the setting of cerebral ischemia-reperfusion injury.

Side effects

When compared with propofol, side effects such as pain on injection and respiratory depression appear to be less common with ciprofol.

Pharmacology

Pharmacokinetics

Metabolism of ciprofol occurs primarily in the liver through oxidation, glucuronidation, and sulfation, resulting in the formation of the inactive metabolite M4-glucuronide, which is excreted renally. It is not necessary to adjust the dose in people with mild or moderate renal impairment, or in those with mild or moderate hepatic impairment. In elderly people, a slightly lower dose (0.3 mg/kg) appears to be similar in efficacy to the higher doses administered to younger people but is associated with fewer adverse effects.

Ciprofol has a short elimination half-life, generally between 2 and 4 hours. Owing to its rapid metabolism and high clearance, the drug does not tend to accumulate in the body, even during prolonged infusions.

Pharmacodynamics

Compared to propofol, ciprofol exhibits stronger binding to the GABAA receptor and elicits a greater enhancement of GABAA receptor-mediated neurotransmission. It also acts as a SIRT1 activator.

Ciprofol exhibits pharmacodynamic properties similar to those of propofol, including both rapid onset and rapid offset. Ciprofol appears to have similar effects upon the respiratory and cardiovascular systems as those propofol.

Biodegradation and toxicity

Ciprofol is characterized by a rapid onset of action, and predictable absorption, distribution, metabolism, excretion processes. The compound undergoes glucuronidation in the liver, followed by excretion by the kidneys.

References

  1. 1 2 3 "Sichuan Haisco Pharmaceutical". AdisInsight. 28 August 2024. Retrieved 1 October 2025.
  2. 1 2 "Novel Drug Approvals for 2026". U.S. Food and Drug Administration (FDA). 29 May 2026. Retrieved 31 May 2026.
  3. ↑ "Ciprofol (Cipepofol): A γ-Aminobutyric Acid Receptor Agonist for Induction of Anesthesia". Chemistry and Pharmacology of Drug Discovery. Wiley. 2024. pp. 251–274. doi:10.1002/9781394225156.ch12. ISBN 978-1-394-22512-5. Retrieved 1 October 2025.
  4. 1 2 Wang X, Wang X, Liu J, Zuo YX, Zhu QM, Wei XC, et al. (March 2022). "Effects of ciprofol for the induction of general anesthesia in patients scheduled for elective surgery compared to propofol: a phase 3, multicenter, randomized, double-blind, comparative study". European Review for Medical and Pharmacological Sciences. 26 (5): 1607–1617. PMID 35302207.
  5. 1 2 Zeng Y, Wang DX, Lin ZM, Liu J, Wei XC, Deng J, et al. (February 2022). "Efficacy and safety of HSK3486 for the induction and maintenance of general anesthesia in elective surgical patients: a multicenter, randomized, open-label, propofol-controlled phase 2 clinical trial". European Review for Medical and Pharmacological Sciences. 26 (4): 1114–1124. PMID 35253166.
  6. ↑ Liao J, Li M, Huang C, Yu Y, Chen Y, Gan J, et al. (2022). "Pharmacodynamics and Pharmacokinetics of HSK3486, a Novel 2,6-Disubstituted Phenol Derivative as a General Anesthetic". Frontiers in Pharmacology. 13 830791. doi:10.3389/fphar.2022.830791. PMC 8851058. PMID 35185584.
  7. 1 2 3 Chen BZ, Yin XY, Jiang LH, Liu JH, Shi YY, Yuan BY (August 2022). "The efficacy and safety of ciprofol use for the induction of general anesthesia in patients undergoing gynecological surgery: a prospective randomized controlled study". BMC Anesthesiology. 22 (1) 245. doi:10.1186/s12871-022-01782-7. PMC 9347095. PMID 35922771.
  8. ↑ Lu M, Liu J, Wu X, Zhang Z (2023). "Ciprofol: A Novel Alternative to Propofol in Clinical Intravenous Anesthesia?". BioMed Research International. 2023 7443226. doi:10.1155/2023/7443226. PMC 9879693. PMID 36714027.
  9. 1 2 Qin L, Ren L, Wan S, Liu G, Luo X, Liu Z, et al. (May 2017). "Design, Synthesis, and Evaluation of Novel 2,6-Disubstituted Phenol Derivatives as General Anesthetics". Journal of Medicinal Chemistry. 60 (9): 3606–3617. doi:10.1021/acs.jmedchem.7b00254. PMID 28430430.
  10. ↑ Nair A, Seelam S (2022). "Ciprofol- a game changing intravenous anesthetic or another experimental drug!". Saudi Journal of Anaesthesia. 16 (2): 258–259. doi:10.4103/sja.sja_898_21. PMC 9009555. PMID 35431734.
  11. ↑ Man Y, Xiao H, Zhu T, Ji F (March 2023). "Study on the effectiveness and safety of ciprofol in anesthesia in gynecological day surgery: a randomized double-blind controlled study". BMC Anesthesiology. 23 (1) 92. doi:10.1186/s12871-023-02051-x. PMC 10039513. PMID 36964501.
  12. ↑ Qin K, Qin WY, Ming SP, Ma XF, Du XK (July 2022). "Effect of ciprofol on induction and maintenance of general anesthesia in patients undergoing kidney transplantation". European Review for Medical and Pharmacological Sciences. 26 (14): 5063–5071. PMID 35916802.
  13. 1 2 Luo Z, Tu H, Zhang X, Wang X, Ouyang W, Wei X, et al. (March 2022). "Efficacy and Safety of HSK3486 for Anesthesia/Sedation in Patients Undergoing Fiberoptic Bronchoscopy: A Multicenter, Double-Blind, Propofol-Controlled, Randomized, Phase 3 Study". CNS Drugs. 36 (3): 301–313. doi:10.1007/s40263-021-00890-1. PMC 8927014. PMID 35157236.
  14. ↑ Wu B, Zhu W, Wang Q, Ren C, Wang L, Xie G (2022). "Efficacy and safety of ciprofol-remifentanil versus propofol-remifentanil during fiberoptic bronchoscopy: A prospective, randomized, double-blind, non-inferiority trial". Frontiers in Pharmacology. 13 1091579. doi:10.3389/fphar.2022.1091579. PMC 9812563. PMID 36618929.
  15. ↑ Li J, Wang X, Liu J, Wang X, Li X, Wang Y, et al. (August 2022). "Comparison of ciprofol (HSK3486) versus propofol for the induction of deep sedation during gastroscopy and colonoscopy procedures: A multi-centre, non-inferiority, randomized, controlled phase 3 clinical trial". Basic & Clinical Pharmacology & Toxicology. 131 (2): 138–148. doi:10.1111/bcpt.13761. PMC 9543620. PMID 35653554.
  16. ↑ Long YQ, Feng CD, Ding YY, Feng XM, Liu H, Ji FH, et al. (2022). "Esketamine as an Adjuvant to Ciprofol or Propofol Sedation for Same-Day Bidirectional Endoscopy: Protocol for a Randomized, Double-Blind, Controlled Trial With Factorial Design". Frontiers in Pharmacology. 13 821691. doi:10.3389/fphar.2022.821691. PMC 8975265. PMID 35370640.
  17. ↑ Liu Y, Yu X, Zhu D, Zeng J, Lin Q, Zang B, et al. (May 2022). "Safety and efficacy of ciprofol vs. propofol for sedation in intensive care unit patients with mechanical ventilation: a multi-center, open label, randomized, phase 2 trial". Chinese Medical Journal. 135 (9): 1043–1051. doi:10.1097/CM9.0000000000001912. PMC 9276409. PMID 34924506.
  18. ↑ Liu GL, Wu GZ, Ge D, Zhou HJ, Cui S, Gao K, et al. (2023). "Efficacy and safety of ciprofol for agitation and delirium in the ICU: A multicenter, single-blind, 3-arm parallel randomized controlled trial study protocol". Frontiers in Medicine. 9 1024762. doi:10.3389/fmed.2022.1024762. PMC 9868613. PMID 36698817.
  19. ↑ Wang YC, Wu MJ, Zhou SL, Li ZH (January 2023). "Protective effects of combined treatment with ciprofol and mild therapeutic hypothermia during cerebral ischemia-reperfusion injury". World Journal of Clinical Cases. 11 (3): 487–492. doi:10.12998/wjcc.v11.i3.487. PMC 9923870. PMID 36793629.
  20. ↑ Hu C, Ou X, Teng Y, Shu S, Wang Y, Zhu X, et al. (November 2021). "Sedation Effects Produced by a Ciprofol Initial Infusion or Bolus Dose Followed by Continuous Maintenance Infusion in Healthy Subjects: A Phase 1 Trial". Advances in Therapy. 38 (11): 5484–5500. doi:10.1007/s12325-021-01914-4. PMC 8523013. PMID 34559359.
  21. 1 2 Vittori A, Di Fabio C, Cascella M, Marinangeli F, Francia E, Mascilini I, et al. (January 2026). "Advantages of Ciprofol with Special Consideration of Pediatric Anesthesia". Children. 13 (2): 188. doi:10.3390/children13020188. PMC 12939459. PMID 41749542.
  22. ↑ Liu SB, Yao X, Tao J, Yang JJ, Zhao YY, Liu DW, et al. (March 2023). "Population total and unbound pharmacokinetics and pharmacodynamics of ciprofol and M4 in subjects with various renal functions". British Journal of Clinical Pharmacology. 89 (3): 1139–1151. doi:10.1111/bcp.15561. PMID 36217805. S2CID 252818288.
  23. ↑ Hu Y, Li X, Liu J, Chen H, Zheng W, Zhang H, et al. (December 2022). "Safety, pharmacokinetics and pharmacodynamics of a novel γ-aminobutyric acid (GABA) receptor potentiator, HSK3486, in Chinese patients with hepatic impairment". Annals of Medicine. 54 (1): 2769–2780. doi:10.1080/07853890.2022.2129433. PMC 9559057. PMID 36217101.
  24. ↑ Li X, Yang D, Li Q, Wang H, Wang M, Yan P, et al. (2021). "Safety, Pharmacokinetics, and Pharmacodynamics of a Single Bolus of the γ-aminobutyric Acid (GABA) Receptor Potentiator HSK3486 in Healthy Chinese Elderly and Non-elderly". Frontiers in Pharmacology. 12 735700. doi:10.3389/fphar.2021.735700. PMC 8430033. PMID 34512361.
  25. ↑ Ding YY, Long YQ, Yang HT, Zhuang K, Ji FH, Peng K (December 2022). "Efficacy and safety of ciprofol for general anaesthesia induction in elderly patients undergoing major noncardiac surgery: A randomised controlled pilot trial". European Journal of Anaesthesiology. 39 (12): 960–963. doi:10.1097/EJA.0000000000001759. PMID 36214498. S2CID 252779399.
  26. ↑ Duan G, Lan H, Shan W, Wu Y, Xu Q, Dong X, et al. (April 2023). "Clinical effect of different doses of ciprofol for induction of general anesthesia in elderly patients: A randomized, controlled trial". Pharmacology Research & Perspectives. 11 (2) e01066. doi:10.1002/prp2.1066. PMC 9944862. PMID 36811327. S2CID 257098376.
  27. ↑ Yang Y, Xia Z, Xu C, Zhai C, Yu X, Li S (2022). "Ciprofol attenuates the isoproterenol-induced oxidative damage, inflammatory response and cardiomyocyte apoptosis". Frontiers in Pharmacology. 13 1037151. doi:10.3389/fphar.2022.1037151. PMC 9723392. PMID 36483733.
  28. ↑ Bian Y, Zhang H, Ma S, Jiao Y, Yan P, Liu X, et al. (January 2021). "Mass balance, pharmacokinetics and pharmacodynamics of intravenous HSK3486, a novel anaesthetic, administered to healthy subjects". British Journal of Clinical Pharmacology. 87 (1): 93–105. doi:10.1111/bcp.14363. PMID 32415708. S2CID 218658207.

Further reading