1. Apoptosis MAPK/ERK Pathway
  2. RIP kinase Mixed Lineage Kinase Necroptosis
  3. SZM-1209

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.

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SZM-1209 Chemical Structure

SZM-1209 Chemical Structure

CAS No. : 2919801-86-6

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Description

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].

IC50 & Target

RIPK1

85 nM (Kd)

RIPK3

>10000 nM (Kd)

In Vitro

SZM-1209 blocks necroptosis in a dose-dependent manner[1].
SZM-1209 (0-1 μM, 6 h) specifically inhibits phosphorylation of RIPK1-RIPK3-MLKL necroptosis signaling[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis[1]

Cell Line: HT-29 cells
Concentration: 0.1, 0.5, and 1 μM
Incubation Time: 6 h
Result: SZM-1209 at 1 μM completely inhibited phosphorylation of both RIPK1 and RIPK3 in 2-6 h, and subsequently inhibited the phosphorylation of downstream MLKL.
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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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.
Molecular Weight

696.71

Formula

C31H29F5N4O5S2

CAS No.
SMILES

CCS(=O)(NC1CCC(CC1)C(NC2=NC3=C(S2)C=C(C(F)=C3)OC4=CC=C(C(NC(CC5=CC=CC(C(F)(F)F)=C5)=O)=C4)F)=O)=O

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation
References
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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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Product Name:
SZM-1209
Cat. No.:
HY-149052
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