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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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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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
InChI Key YCNMAPLPQYQJFC-ZDUSSCGKSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
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]