| Field | Specification |
|---|---|
| Target | |
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C27H18F5N3O5S |
| Purity | |
| SMILES | |
| Form | Solid |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
SZM679 is a potent, orally active, selective inhibitor of RIPK1, with Kd values of 8.6 nM for RIPK1 and >5000 nM for RIPK3. It reverses the tumor necrosis factor-induced systemic inflammatory response and decreases Tau hyperphosphorylation, neuroinflammation, and RIPK1 phosphorylation levels in the hippocampus and cortex, and can be used in Alzheimer's disease (AD) research[1]. It is supplied as an off-white to light yellow solid (C27H18F5N3O5S, MW 591.51) at 99.59% purity.
Physical & Chemical Properties
| CAS Number | 3027645-52-6 |
|---|---|
| Molecular Formula | C27H18F5N3O5S |
| Molecular Weight | 591.51 g/mol |
| Purity | 99.59% |
| Appearance | Solid |
| Color | Off-white to light yellow |
| SMILES | O=C(C1CC(C1)=O)NC2=NC3=CC(F)=C(OC4=CC=C(F)C(NC(CC5=CC=CC(OC(F)(F)F)=C5)=O)=C4)C=C3S2 |
| Target | RIPK1, RIPK3 |
| Signaling Pathway | Apoptosis |
| Solubility | In Vitro: DMSO: 125 mg/mL (211.32 mM; Requires sonication; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) |
| Storage | Powder: -20°C, 3 years. In solvent: -80°C, 6 months; -20°C, 1 month. |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Biological Activity
IC50 & Target[1]
|
RIPK1 8.6 nM (Kd) |
RIPK3 >5000 nM (Kd) |
Literature Cited
Sources cited in this description and in the In Vitro & In Vivo Data tab. Peer-reviewed publications that used this product are listed under References.
Safety
For Research Use Only. Not for use in diagnostic or therapeutic procedures, and not for human or veterinary use. Handle in accordance with the Safety Data Sheet and your institution's chemical hygiene plan.
In Vitro
| Solvent | Solubility | Notes |
|---|---|---|
| DMSO | 125 mg/mL (211.32 mM) | requires sonication; use freshly opened DMSO (absorbed moisture lowers solubility) |
Aliquot the stock solution and store it at -80°C (up to 6 months) or -20°C (up to 1 month); avoid repeated freeze-thaw cycles.
Data provided by the manufacturer.
In Vitro
SZM679 (0-10 μM; 24 h; necrotic L929 and HT-29 cells) has anti-necrosis activity through inhibition of the RIPK1 pathway, with an EC50 value of 2 nM. SZM679 also protects against necroptosis induced by TNF-α, cycloheximide, and z-VAD-fmk (TCZ). SZM679 protects against TZ-induced necroptosis dose-dependently[1]. In necrotic HT-29 cells, SZM679 (1 μM; 6 h) selectively inhibits RIPK1 expression but not RIPK3 or MLKL. By inhibiting TSZ-induced phosphorylation of RIPK1, SZM679 blocks necrosome formation[1].
Western Blot Analysis[1]
| Cell Line | Necrotic HT-29 cells |
|---|---|
| Concentration | 1 μM |
| Incubation Time | 6 hours |
| Result | Inhibited the phosphorylation of RIPK1 at 1 μM, resulting in the inhibition of the downstream phosphorylation of RIPK3 and MLKL. |
In Vivo
In male C57BL/6 J mice with TNF-induced SIRS models, SZM679 (10-40 mg/kg; i.p.) provides in vivo protection against necroptosis-specific TNF-induced systemic inflammatory response syndrome (SIRS)[1]. Administered intragastrically at 1 mg/kg once daily for 7 days, SZM679 improves cognitive function in STZ-induced AD mice[1]. Under the same regimen (1 mg/kg intragastrically, once daily for 7 days), SZM679 rescues brain structure damage without obvious toxicity, decreases AD biomarkers and inflammatory cytokine expression levels, and inhibits RIPK1 phosphorylation in brain tissues of AD mice[1].
| Animal Model | Male C57BL/6 J mice with TNF-induced SIRS models[1] |
|---|---|
| Dosage | 10, 20, and 40 mg/kg |
| Administration | Intraperitoneal injection |
| Result | Protected mice in a dose-dependent manner from hypothermia and death. |
| Animal Model | Male C57BL/6 J mice with AD models[1] |
|---|---|
| Dosage | 1 mg/kg |
| Administration | Administered intragastrically; once daily for 7 days |
| Result | Improved the anxiety, behavior, and exploratory ability of AD mice. Improved the learning and memory ability of AD mice. |
| Animal Model | Male C57BL/6 J mice with AD models[1] |
|---|---|
| Dosage | 1 mg/kg |
| Administration | Administered intragastrically; once daily for 7 days |
| Result | Rescued the damaged hippocampal structure of AD mice and restored the cell number and morphology. Down-regulated the expression of the inflammatory cytokines, the IL-1β and TNF-α levels. |
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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