Selonsertib Chemical Properties

Melting point:

>180°C (dec.)

Density 

1.39±0.1 g/cm3(Predicted)

storage temp. 

-20°C

solubility 

Soluble in DMSO (>25 mg/ml)

pka

11.21±0.70(Predicted)

form 

solid

color 

White

Stability:

Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.

InChIKey

YIDDLAAKOYYGJG-UHFFFAOYSA-N

SMILES

C(NC1=NC(C2N(C(C)C)C=NN=2)=CC=C1)(=O)C1=CC(N2C=NC(C3CC3)=C2)=C(C)C=C1F

CAS DataBase Reference

1448428-04-3

Selonsertib Usage And Synthesis

Description

Selonsertib (1448428-04-3) is a potent Apoptosis signal-regulating kinase 1 (ASK1) inhibitor (pIC50 = 8.3)1 found to improve metabolic parameters in nonalcoholic steatohepatitis, reduce hepatic steatosis, inflammation, and fibrosis2-4. Selonsertib suppressed the efflux function of multidrug resistance (MDR) transporters ABCB1 and ABCG2.5

Uses

Selonsertib is an apoptosis signal-regulating kinase 1 (ASK1) inhibitor with potential anti-inflammatory, antineoplastic and anti-fibrotic activities. Selonsertib interacts with the catalytic kinase domain of ASK1 and prevents its phosphorylation and activation. As a result, the expression of genes involved in fibrosis, cellular proliferation, and apoptosis are down regulated.

in vitro

gs-4997 has been identified as a highly selective and potent ask1 inhibitor that competed with atp in the ask1 catalytic kinase domain. moreover, the ask1 inhibition caused by gs-4997 was found to be significantly different in mechanism from bardoxolone methyl. gs- 4997 could also shut down cell signaling involved in pathogenesis, while bardoxolone methyl activated mrna transcription in every cell exposed to drug. in addition, gs-4997 could selectively target affected cells in which the oxidative burden was high [1].

IC 50

ASK1: 8.3 (pIC₅₀)

References

[1] MARION LANIER*. Structure-Based Design of ASK1 Inhibitors as Potential Agents for Heart Failure[J]. ACS Medicinal Chemistry Letters, 2017, 8 3: 316-320. DOI:10.1021/acsmedchemlett.6b00481
[2] ROHIT LOOMBA. The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: A randomized, phase 2 trial[J]. Hepatology, 2017, 67 2: 549-559. DOI:10.1002/hep.29514
[3] ZOBAIR M. YOUNOSSI. Improvement of hepatic fibrosis and patient-reported outcomes in non-alcoholic steatohepatitis treated with selonsertib[J]. Liver International, 2018, 38 10: 1849-1859. DOI:10.1111/liv.13706
[4] SAMER GAWRIEH MD  Naga C M. Emerging Treatments for Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis[J]. Clinics in liver disease, 2018, 22 1: Pages 189-199. DOI:10.1016/j.cld.2017.08.013
[5] NING JI . Selonsertib (GS-4997), an ASK1 inhibitor, antagonizes multidrug resistance in ABCB1- and ABCG2-overexpressing cancer cells[J]. Cancer letters, 2019, 440: Pages 82-93. DOI:10.1016/j.canlet.2018.10.007

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