Synonym
ATB346; ATB-346; ATB 346; HS-naproxen;
IUPAC/Chemical Name
4-carbamothioylphenyl 2-(6-methoxynaphthalen-2-yl)propanoate.
InChi Key
YCNMAPLPQYQJFC-UHFFFAOYSA-N
InChi Code
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)
SMILES Code
CC(C1=CC=C2C=C(OC)C=CC2=C1)C(OC3=CC=C(C(N)=S)C=C3)=O
Appearance
Light yellow solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
ATB-346 inhibits cyclooxygenase-1 and 2 (COX-1 and 2).
In vitro activity:
A375 human melanoma cells were treated with ATB-346, TBZ or naproxen (100 μM for 24 and 48 h) and apoptosis was determined by annexinV/PI staining, which detects the externalization of phosphatidylserine (PS), a characteristic feature of cells entering apoptosis. This dual staining distinguishes between unaffected cells (unlabeled; quadrant 3, Fig. 1A), early apoptotic cells (annexin V positive; quadrant 4, Fig. 1A), late apoptotic cells (annexin V positive, PI positive; quadrant 2, Fig. 1A), and necrotic (PI positive; quadrant 1, Fig. 1A). As shown in Fig. 1B only ATB-346 induced apoptosis of A375 cell in a time-dependent manner (18% and 24% at 24 and 48 h respectively). The pro-apoptotic effect of ATB-346 was confirmed by the time-dependent cleavage of caspase 3, the main effector caspase, and of its substrate poly (adenosine diphosphate-ribose) polymerase (PARP) (Fig. 1C).
Reference: Pharmacol Res. 2016 Dec;114:67-73. https://pubmed.ncbi.nlm.nih.gov/27777130/
In vivo activity:
APCMin/+ mice treated daily for 14 days (during the 6th and 7th weeks of life) with naproxen at a dose of 1 mg/kg (4.3 μmol/kg) had similar numbers of polyps as vehicle-treated APCMin/+ mice (Fig 2). In contrast, daily treatment with ATB-346 at an equimolar dose resulted in 51% reduction (p<0.01) in the total polyp score. With a higher dose of naproxen (10 mg/kg; 43 μmol/kg), a marked reduction (57%; p<0.001) of the total polyp score was observed. However, treatment with an equimolar dose of ATB-346 reduced the total polyp score by 98%, significantly greater than the effect of naproxen.
Reference: PLoS One. 2016; 11(2): e0147289. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766010/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
62.3 |
170.48 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
365.44
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. De Cicco P, Panza E, Ercolano G, Armogida C, Sessa G, Pirozzi G, Cirino G, Wallace JL, Ianaro A. ATB-346, a novel hydrogen sulfide-releasing anti-inflammatory drug, induces apoptosis of human melanoma cells and inhibits melanoma development in vivo. Pharmacol Res. 2016 Dec;114:67-73. doi: 10.1016/j.phrs.2016.10.019. Epub 2016 Oct 21. PMID: 27777130.
3. Paul-Clark M, Elsheikh W, Kirkby N, Chan M, Devchand P, Agbor TA, Flannigan KL, Cheadle C, Freydin M, Ianaro A, Mitchell JA, Wallace JL. Profound Chemopreventative Effects of a Hydrogen Sulfide-Releasing NSAID in the APCMin/+ Mouse Model of Intestinal Tumorigenesis. PLoS One. 2016 Feb 24;11(2):e0147289. doi: 10.1371/journal.pone.0147289. PMID: 26910063; PMCID: PMC4766010.
4. Herrera BS, Coimbra LS, da Silva AR, Teixeira SA, Costa SK, Wallace JL, Spolidorio LC, Muscara MN. The H2S-releasing naproxen derivative, ATB-346, inhibits alveolar bone loss and inflammation in rats with ligature-induced periodontitis. Med Gas Res. 2015 Feb 27;5:4. doi: 10.1186/s13618-015-0025-3. PMID: 25755876; PMCID: PMC4353461.
In vitro protocol:
1. De Cicco P, Panza E, Ercolano G, Armogida C, Sessa G, Pirozzi G, Cirino G, Wallace JL, Ianaro A. ATB-346, a novel hydrogen sulfide-releasing anti-inflammatory drug, induces apoptosis of human melanoma cells and inhibits melanoma development in vivo. Pharmacol Res. 2016 Dec;114:67-73. doi: 10.1016/j.phrs.2016.10.019. Epub 2016 Oct 21. PMID: 27777130.
In vivo protocol:
1. Paul-Clark M, Elsheikh W, Kirkby N, Chan M, Devchand P, Agbor TA, Flannigan KL, Cheadle C, Freydin M, Ianaro A, Mitchell JA, Wallace JL. Profound Chemopreventative Effects of a Hydrogen Sulfide-Releasing NSAID in the APCMin/+ Mouse Model of Intestinal Tumorigenesis. PLoS One. 2016 Feb 24;11(2):e0147289. doi: 10.1371/journal.pone.0147289. PMID: 26910063; PMCID: PMC4766010.
2. Herrera BS, Coimbra LS, da Silva AR, Teixeira SA, Costa SK, Wallace JL, Spolidorio LC, Muscara MN. The H2S-releasing naproxen derivative, ATB-346, inhibits alveolar bone loss and inflammation in rats with ligature-induced periodontitis. Med Gas Res. 2015 Feb 27;5:4. doi: 10.1186/s13618-015-0025-3. PMID: 25755876; PMCID: PMC4353461.
1: Elsheikh W, Blackler RW, Flannigan KL, Wallace JL. Enhanced chemopreventive effects of a hydrogen sulfide-releasing anti-inflammatory drug (ATB-346) in experimental colorectal cancer. Nitric Oxide. 2014 Apr 18. pii: S1089-8603(14)00204-3. doi: 10.1016/j.niox.2014.04.006. [Epub ahead of print] PubMed PMID: 24747869.
2: Ekundi-Valentim E, Mesquita FP, Santos KT, de Paula MA, Florenzano J, Zanoni CI, Rodrigues L, de Nucci G, Teixeira SA, Ferreira HH, Wallace JL, Costa SK, Muscará MN. A comparative study on the anti-inflammatory effects of single oral doses of naproxen and its hydrogen sulfide (H2S)-releasing derivative ATB-346 in rats with carrageenan-induced synovitis. Med Gas Res. 2013 Nov 16;3(1):24. doi: 10.1186/2045-9912-3-24. PubMed PMID: 24237604; PubMed Central PMCID: PMC3843537.
3: Campolo M, Esposito E, Ahmad A, Di Paola R, Wallace JL, Cuzzocrea S. A hydrogen sulfide-releasing cyclooxygenase inhibitor markedly accelerates recovery from experimental spinal cord injury. FASEB J. 2013 Nov;27(11):4489-99. doi: 10.1096/fj.13-234716. Epub 2013 Jul 30. PubMed PMID: 23901068.
4: Blackler R, Syer S, Bolla M, Ongini E, Wallace JL. Gastrointestinal-sparing effects of novel NSAIDs in rats with compromised mucosal defence. PLoS One. 2012;7(4):e35196. doi: 10.1371/journal.pone.0035196. Epub 2012 Apr 9. PubMed PMID: 22496907; PubMed Central PMCID: PMC3322164.
5: Wallace JL, Caliendo G, Santagada V, Cirino G. Markedly reduced toxicity of a hydrogen sulphide-releasing derivative of naproxen (ATB-346). Br J Pharmacol. 2010 Mar;159(6):1236-46. doi: 10.1111/j.1476-5381.2009.00611.x. Epub 2010 Feb 1. PubMed PMID: 20128814; PubMed Central PMCID: PMC2848928.
