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Otenaproxesul

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Otenaproxesul
Clinical data
Other namesATB-352[1]
Routes of
administration
By mouth
ATC code
  • None
Legal status
Legal status
Identifiers
  • 4-Carbamothioylphenyl (2S)-2-(6-methoxy-2-naphthyl)propanoate
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC21H19NO3S
Molar mass365.45 g·mol−1
3D model (JSmol)
  • COC1=CC2=CC=C(C=C2C=C1)C(C)C(=O)OC3=CC=C(C=C3)C(N)=S
  • InChI=1S/C21H19NO3S/c1-13(21(23)25-18-8-5-14(6-9-18)20(22)26)15-3-4-17-12-19(24-2)10-7-16(17)11-15/h3-13H,1-2H3,(H2,22,26)/t13-/m0/s1
  • Key:YCNMAPLPQYQJFC-ZDUSSCGKSA-N

Otenaproxesul is a analgesic and anti-inflammatory drug being developed by Antibe Therapeutics. An NSAID structurally derived from naproxen, in 2016 it received approval to commence phase II clinical trials as a treatment for osteoarthritis after completing phase I clinical trials in 2015.[2] In 2018, the drug completed trials for gastrointestinal safety, and in 2020 completed phase IIb trials on efficacy of pain reduction.[3] Initial phase III clinical trials in 2021 failed to meet the necessary criteria to advance to the next phase.

Other in vivo studies have demonstrated a reduction in zymosan-induced pain and inflammation and cytokine-induced bone loss.[4] Preclinical studies have also investigated the treatment of melanoma, intestinal cancer,[5] and periodontitis.[6]

Pharmacology

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Like other NSAIDs, otenaproxesul acts as an inhibitor of the cycloxygenase (COX) enzymes, suppressing the production of prostaglandins. Additionally, it releases hydrogen sulfide in the gastrointestinal tract, reducing gastrointestinal adverse effects such as ulcers.[7]

References

[edit]
  1. ^ "4-Carbamothioylphenyl 2-(6-methoxynaphthalen-2-yl)propanoate". PubChem. National Institute of Health. Retrieved February 9, 2021.
  2. ^ "Otenaproxesul". IUPHAR/BPS Guide to Pharmacology. January 27, 2021.
  3. ^ "Otenaproxesul (ATB-346)". Antibe Therapeutics. 19 July 2019. Retrieved February 17, 2021.
  4. ^ "Otenaproxesul, (+/-)-". National Center for Advancing Translational Sciences. Retrieved February 9, 2021.
  5. ^ Elsheikh W, Blackler RW, Flannigan KL, Wallace JL (September 15, 2014). "Enhanced chemopreventive effects of a hydrogen sulfide-releasing anti-inflammatory drug (ATB-346) in experimental colorectal cancer". Nitric Oxide. 41: 131–7. doi:10.1016/j.niox.2014.04.006. PMID 24747869 – via PubMed.
  6. ^ Gugliandolo E, Fusco R, D'Amico R, Militi A, Oteri G, Wallace JL, et al. (June 2018). "Anti-inflammatory effect of ATB-352, a H2S -releasing ketoprofen derivative, on lipopolysaccharide-induced periodontitis in rats". Pharmacological Research. 132: 220–231. doi:10.1016/j.phrs.2017.12.022. PMID 29287688. S2CID 12099369.
  7. ^ Costa SK, Muscara MN, Allain T, Dallazen J, Gonzaga L, Buret AG, et al. (November 2020). "Enhanced Analgesic Effects and Gastrointestinal Safety of a Novel, Hydrogen Sulfide-Releasing Anti-Inflammatory Drug (ATB-352): A Role for Endogenous Cannabinoids". Antioxidants & Redox Signaling. 33 (14): 1003–1009. doi:10.1089/ars.2019.7884. PMC 7578177. PMID 32064887.