otenaproxesul   Click here for help

GtoPdb Ligand ID: 9534

Synonyms: ATB 346 | ATB-346 | ATB-346, (S)- | ATB346
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Otenaproxesul (ATB-346) is a novel, orally administered, gastrointestinal-sparing hydrogen sulfide (H2S)-releasing analgesic and anti-inflammatory drug in clinical trials for osteoarthritis [8]. Structurally it comprises an H2S-releasing moiety covalently linked to a NSAID (naproxen). H2S-releasing NSAIDs are in development for their potential analgesic, anti-inflammatory, cytoprotective and chemopreventative properties [2-3,5-6,9-10].
2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 2
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 93.64
Molecular weight 365.11
XLogP 4.19
No. Lipinski's rules broken 0
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Canonical SMILES COc1ccc2c(c1)ccc(c2)C(C(=O)Oc1ccc(cc1)C(=S)N)C
Isomeric SMILES COc1ccc2c(c1)ccc(c2)[C@@H](C(=O)Oc1ccc(cc1)C(=S)N)C
InChI 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
1. Blackler R, Syer S, Bolla M, Ongini E, Wallace JL. (2012)
Gastrointestinal-sparing effects of novel NSAIDs in rats with compromised mucosal defence.
PLoS ONE, 7 (4): e35196. [PMID:22496907]
2. De Cicco P, Panza E, Ercolano G, Armogida C, Sessa G, Pirozzi G, Cirino G, Wallace JL, Ianaro A. (2016)
ATB-346, a novel hydrogen sulfide-releasing anti-inflammatory drug, induces apoptosis of human melanoma cells and inhibits melanoma development in vivo.
Pharmacol Res, 114: 67-73. [PMID:27777130]
3. Elsheikh W, Blackler RW, Flannigan KL, Wallace JL. (2014)
Enhanced chemopreventive effects of a hydrogen sulfide-releasing anti-inflammatory drug (ATB-346) in experimental colorectal cancer.
Nitric Oxide, 41: 131-7. [PMID:24747869]
4. Fomenko I, Sklyarov A, Bondarchuk T, Biletska L, Panasyuk N, Wallace JL. (2014)
Effects of conventional and hydrogen sulfide-releasing non-steroidal anti-inflammatory drugs in rats with stress-induced and epinephrine-induced gastric damage.
Stress, 17 (6): 528-37. [PMID:25238023]
5. Gemici B, Elsheikh W, Feitosa KB, Costa SK, Muscara MN, Wallace JL. (2015)
H2S-releasing drugs: anti-inflammatory, cytoprotective and chemopreventative potential.
Nitric Oxide, 46: 25-31. [PMID:25461269]
6. Szabo C, Papapetropoulos A. (2017)
International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H2S Levels: H2S Donors and H2S Biosynthesis Inhibitors.
Pharmacol Rev, 69 (4): 497-564. [PMID:28978633]
7. Wallace JL, Caliendo G, Santagada V, Cirino G. (2010)
Markedly reduced toxicity of a hydrogen sulphide-releasing derivative of naproxen (ATB-346).
Br J Pharmacol, 159 (6): 1236-46. [PMID:20128814]
8. Wallace JL, Nagy P, Feener TD, Allain T, Ditrói T, Vaughan DJ, Muscara MN, de Nucci G, Buret AG. (2020)
A proof-of-concept, Phase 2 clinical trial of the gastrointestinal safety of a hydrogen sulfide-releasing anti-inflammatory drug.
Br J Pharmacol, 177 (4): 769-777. [PMID:30834513]
9. Wallace JL, Vaughan D, Dicay M, MacNaughton WK, de Nucci G. (2018)
Hydrogen Sulfide-Releasing Therapeutics: Translation to the Clinic.
Antioxid Redox Signal, 28 (16): 1533-1540. [PMID:28388861]
10. Zheng Y, Ji X, Ji K, Wang B. (2015)
Hydrogen sulfide prodrugs-a review.
Acta Pharm Sin B, 5 (5): 367-77. [PMID:26579468]