| Identification | Back Directory | [Name]
Benzeneacetamide, N-[5-[[2-[[[4-[(ethylsulfonyl)amino]cyclohexyl]carbonyl]amino]-5-fluoro-6-benzothiazolyl]oxy]-2-fluorophenyl]-3-(trifluoromethyl)- | [CAS]
2919801-86-6 | [Synonyms]
SZM-1209
Benzeneacetamide, N-[5-[[2-[[[4-[(ethylsulfonyl)amino]cyclohexyl]carbonyl]amino]-5-fluoro-6-benzothiazolyl]oxy]-2-fluorophenyl]-3-(trifluoromethyl)- | [Molecular Formula]
C31H29F5N4O5S2 | [MOL File]
2919801-86-6.mol | [Molecular Weight]
696.71 |
| Hazard Information | Back Directory | [Uses]
SZM-1209 is an orally active, potent and specific RIPK1 inhibitor, with a Kd of 85 nM. SZM-1209 exhibits high anti-necroptotic activity (EC50=22.4 ± 8.1 nM). SZM-1209 shows anti-SIRS (systemic inflammatory response syndrome), and anti-ALI (acute lung injury) effects[1]. | [in vivo]
SZM-1209 (25-100 mg/kg, IG) can reverse mouse deaths with significant anti-inflammatory effects in a mTNF-α-induced systemic inflammatory response syndrome (SIRS) model[1].
SZM-1209 (25-100 mg/kg, IP) significantly alleviates ALI (acute lung injury) by reducing pulmonary edema and pathological damage[1].
| Animal Model: | C57BL/6J mice (female, 6-8 weeks old, mTNF-α (intravenous injection)-induced SIRS model)[1] | | Dosage: | 25, 50, and 100 mg/kg | | Administration: | Intragastric administration | | Result: | Dose-dependently improved survival rates of the SIRS mice to 30, 90, and 100%. Could effectively protect against mTNFα-induced SIRS in vivo. Serum levels of IL-6 and IL-1β were significantly decreased. |
| Animal Model: | C57BL/6J mice (female, 6-8 weeks old, NNK (HY-126477) (65 mg/kg) short-term intratracheal exposure-induced ALI model)[1] | | Dosage: | 25, 50, and 100 mg/kg | | Administration: | IP | | Result: | Exhibited lower levels of IL-6 and TNF-α in BALF than those of model mice. Inhibited the expression of inflammatory genes of IL-6 and TNF-α in lung tissues of mice at a mRNA level. Significant reduced phosphorylation of RIPK1, and also completely blocked at a high dose of 100 mg/kg in lung tissue of ALI model mice. |
| [IC 50]
RIPK1: 85 nM (Kd); RIPK3: >10000 nM (Kd) | [References]
[1] Zhang X, et al. Targeting Receptor-Interacting Protein Kinase 1 by Novel Benzothiazole Derivatives: Treatment of Acute Lung Injury through the Necroptosis Pathway. J Med Chem. 2023 Apr 13;66(7):5261-5278. DOI:10.1021/acs.jmedchem.3c00197 |
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