| Identification | Back Directory | [Name]
Selonsertib | [CAS]
1448428-04-3 | [Synonyms]
GS 4997
GS-4497
CS-2217
Selonsertib
GS-4997;ASK-1
GS4997;GS 4997
GS4997 SELONSERTIB
Selonsertib GS-4997
Selonsertib free base.
Selonsertib (Synonyms: GS-4997)
GS-4997; GS4997; GS 4997; SELONSERTIB FREE BASE.
5-(4-Cyclopropyl-1H-imidazol-1-yl)-2-fluoro-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-methylbenzamide
5-(4-Cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methyl-N-[6-[4-(1-methylethyl)-4H-1,2,4-triazol-3-yl]-2-pyridinyl]benzamide
Benzamide, 5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methyl-N-[6-[4-(1-methylethyl)-4H-1,2,4-triazol-3-yl]-2-pyridinyl]- | [Molecular Formula]
C24H24FN7O | [MDL Number]
MFCD29920355 | [MOL File]
1448428-04-3.mol | [Molecular Weight]
445.49 |
| Chemical Properties | Back Directory | [Melting point ]
>180°C (dec.) | [density ]
1.39±0.1 g/cm3(Predicted) | [storage temp. ]
-20°C | [solubility ]
Soluble in DMSO (>25 mg/ml) | [form ]
solid | [pka]
11.21±0.70(Predicted) | [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 |
| Hazard Information | Back Directory | [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) | [storage]
Store at -20°C | [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 |
|
|