1448428-04-3 Usage
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].
References
Lanier et al. (2017), Structure-Based Design of ASK1 Inhibitors as Potential Agents for Heart Failure; ACS Med. Chem. Lett. 8 316
Loomba et al. (2017), The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: a randomized, phase 2 trial; Hepatology 67 549
Younossi et al. (2018), Improvement of hepatic fibrosis and patient-reported outcomes in non-alcoholic steatohepatitis treated with selonsertib; Liver Int. 38 1849
Gawrieh and Chalasani (2018), Emerging Treatments for Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis; Clin. Liver Dis. 22 189
Ji et al. (2019), Selonsertib (GS-4997), an ASK1 inhibitor, antagonizes multidrug resistance in ABCB1- and ABCG2-overexpressing cancer cells; Cancer Lett. 440-441 82
Check Digit Verification of cas no
The CAS Registry Mumber 1448428-04-3 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,4,4,8,4,2 and 8 respectively; the second part has 2 digits, 0 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 1448428-04:
(9*1)+(8*4)+(7*4)+(6*8)+(5*4)+(4*2)+(3*8)+(2*0)+(1*4)=173
173 % 10 = 3
So 1448428-04-3 is a valid CAS Registry Number.
1448428-04-3Relevant articles and documents
ASK1 INHIBITOR AND PREPARATION METHOD AND USE THEREOF
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Paragraph 0204, (2020/01/02)
The present disclosure relates to a compound as shown in formula (II), a tautomer or a pharmaceutically acceptable salt thereof, and disclosed is the use thereof in preparing a drug for treating an ASK1-associated disease.
SOLID FORMS OF AN ASK1 INHIBITOR
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Page/Page column 70; 71, (2016/07/27)
Crystalline forms of 5-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluoro-4-methylbenzamide (Compound I) were prepared and characterized in the solid state: Also provided are processes of manufacture and methods of using the crystalline forms.
