Utreloxastat

Utreloxastat
Clinical data
Other namesEPI-857; EPI857; PTC-857; PTC857
Routes of
administration		Oral[1][2][3]
Drug classALOX15 inhibitor
Pharmacokinetic data
Elimination half-life20–>33 hours[3]
Identifiers
  • 2,3,5-trimethyl-6-nonylcyclohexa-2,5-diene-1,4-dione
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC18H28O2
Molar mass276.420 g·mol−1
3D model (JSmol)
  • CCCCCCCCCC1=C(C(=O)C(=C(C1=O)C)C)C
  • InChI=1S/C18H28O2/c1-5-6-7-8-9-10-11-12-16-15(4)17(19)13(2)14(3)18(16)20/h5-12H2,1-4H3
  • Key:IJWAQTHZBDBIID-UHFFFAOYSA-N

Utreloxastat (INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, JANTooltip Japanese Accepted Name; developmental code names EPI-857 and PTC-857) is a 15-lipoxygenase (15-LOX; ALOX15) inhibitor which is under development for the treatment of amyotrophic lateral sclerosis (ALS).[1][2][3][4] It was also previously under development for the treatment of Parkinson's disease, but development for this indication was discontinued.[1] The drug is taken orally.[1][2][3]

It acts as a selective inhibitor of 15-LOX, an enzyme involved in inflammation, oxidative stress, and ferroptosis.[4][2][3] By inhibiting 15-LOX, utreloxastat may replenish intracellular glutathione levels and reduce such processes.[2][3] The elimination half-life of utreloxastat is 20 to 25 hours with a single doses and increases to greater than 33 hours with repeated administration.[3]

Utreloxastat is or has been under development by BioElectron Technology and PTC Therapeutics.[1][4] As of April 2025, it is in phase 2 clinical trials for treatment of amyotrophic lateral sclerosis (ALS).[1] It was also under development for the treatment of Parkinson's disease, and reached phase 1 trials for this indication, but development for this use was discontinued.[1] A phase 2 trial of utreloxastat for ALS was terminated early due to failing to meet its primary endpoint of slowing disease progression and due to company decision in March 2025 and there have been no further developmental updates since.[1][2][5]

See also

References

  1. ^ a b c d e f g h "PTC Therapeutics". AdisInsight. 11 April 2025. Retrieved 1 June 2026.
  2. ^ a b c d e f Martinez-Gonzalez L, Sanchez-Santos C, Huang CS, Gil C, Martinez A (May 2026). "Innovative therapies under clinical development for ALS treatment: small molecules". Expert Opin Investig Drugs. 35 (5): 351–367. doi:10.1080/13543784.2026.2667249. hdl:10261/432424. PMID 42046889. Utreloxastat, an oral small-molecule 15-lipoxygenase (15- LO) inhibitor designed to treat ALS by reducing oxidative stress and inhibiting ferroptosis, through the prevention of glutathione depletion, a key antioxidant deficiency in ALS patients that contributes to motor neuron damage. A first-in-human phase 1 double-blind, placebo-controlled trial in 82 healthy volunteers demonstrated acceptable safety and tolerability, enabling clinical progression [54]. The subsequent phase 2 cardinALS trial evaluated utreloxastat over 24 weeks but failed to meet the primary (ALSFRS-R change from baseline) or key secondary (NfL reduction) endpoints despite good safety and tolerability [55]. The trial was early terminated by sponsor decision even though full results are pending.
  3. ^ a b c d e f g Gao L, Giannousis P, Thoolen M, Kaushik D, Latham J, Tansy A, et al. (February 2023). "First-in-Human Studies of Pharmacokinetics and Safety of Utreloxastat (PTC857), a Novel 15-Lipooxygenase Inhibitor for the Treatment of Amyotrophic Lateral Sclerosis". Clin Pharmacol Drug Dev. 12 (2): 141–151. doi:10.1002/cpdd.1203. PMC 10107758. PMID 36516010. Utreloxastat (alkyl-substituted cyclohexadienedione) (Figure 1) is an orally bioavailable small molecule being developed for the treatment of neurodegenerative diseases characterized by high levels of oxidative stress and mitochondrial pathology, such as ALS. Pharmacologically, utreloxastat can be classified as a redox-active inhibitor of ferroptosis; it functions as an inhibitor of 15-LO to reduce oxidative stress and block depletion of reduced glutathione. By inhibiting 15-LO, utreloxastat is expected to slow or prevent neurodegeneration in ALS by preventing ferroptosis.
  4. ^ a b c Li X, Bedlack R (June 2024). "Evaluating emerging drugs in phase II & III for the treatment of amyotrophic lateral sclerosis". Expert Opinion on Emerging Drugs. 29 (2): 93–102. doi:10.1080/14728214.2024.2333420. PMID 38516735. Utreloxastat (PTC-857), developed by PTC Therapeutics, is a small molecule that inhibits 15-lipoxygenase, a key enzyme that mediates oxidative stress and ferroptosis, i.e. iron-dependent cell death. It also appears to have anti-inflammatory effects, as in Parkinson's disease model, Utreloxastat reduced proinflammatory IL-1ß cytokine production by microglial cells. Utreloxastat is under development by PTC Therapeutics. There were no safety concerns when it was given orally to healthy controls at 500 mg per day for 14 days or one time 1000 mg dose [82]. PTC Therapeutics initiated a 24-week, phase 2 RCT study of its efficacy, safety and biomarker effects in April 2022 (NCT05349721).
  5. ^ "PTC Therapeutics Announces Topline Results of CardinALS Trial of Utreloxastat in ALS Patients". PTC Therapeutics, Inc. 26 November 2024.
This article is issued from Wikipedia. The text is available under Creative Commons Attribution-Share Alike 4.0 unless otherwise noted. Additional terms may apply for the media files.