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SPL-334

Cat. No. M8716
SPL-334 Structure
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Biological Activity

SPL-334 is an inhibitor of S-Nitrosoglutathione reductase (GSNOR), the enzyme responsible for regulating cellular concentrations of S-Nitrosoglutathione (GSNO), which plays a critical role in nitric oxide signaling in the respiratory tract. In a mouse model of allergic airway inflammation, SPL-334 reduced airway hyperreactivity, and in a bleomycin injury model of interstitial lung disease, SPL-334 reduced lung inflammation and fibrosis. Studies for treatment of asthma, idiopathic pulmonary fibrosis (IPF), and inflammation are ongoing.

Chemical Information
Molecular Weight 433.5
Formula C22H15N3O3S2
CAS Number 688347-51-5
Solubility (25°C) DMSO: 20 mg/mL
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
Conversion of different model animals based on BSA (PMID: 27057123)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Kei Hayashida, et al. Improvement in Outcomes After Cardiac Arrest and Resuscitation by Inhibition of S-Nitrosoglutathione Reductase

[2] Irina G Luzina, et al. Pharmacological In Vivo Inhibition of S-Nitrosoglutathione Reductase Attenuates Bleomycin-Induced Inflammation and Fibrosis

[3] Maria E Ferrini, et al. S-nitrosoglutathione reductase inhibition regulates allergen-induced lung inflammation and airway hyperreactivity

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