| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
RIPK1 8.6 nM (Kd) RIPK3 >5000 nM (Kd)
Receptor-interacting protein kinase 1 (RIPK1). SZM679 is a selective RIPK1 inhibitor with a dissociation constant (Kd) of 8.6 nM for RIPK1. It demonstrates minimal off-target activity against RIPK3, with a Kd of greater than 5000 nM. By selectively inhibiting RIPK1, SZM679 blocks the initiation of the necroptotic cell death pathway and reduces downstream inflammatory responses, which are key drivers of many diseases. |
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| ln Vitro |
SZM679 (0-10 μM; 24 h; necrotic L929 and HT-29 cells) inhibits the RIPK1 pathway with an EC50 value of 2 nM, which confers an anti-necrosis effect. Additionally, TNF-α, cycloheximide, and z-VAD-fmk(TCZ)-induced necroptosis are all prevented by SZM679. In a dose-dependent manner, SZM679 guards against TZ-induced necroptosis[1]. Necrotic HT-29 cells treated with SZM679 (1 μM; 6 h) preferentially suppresses RIPK1 expression but not RIPK3 or MLKL. SZM679 prevents the formation of necrosomes by preventing RIPK1 from being phosphorylated by TSZ[1].
SZM679 exhibits potent anti-necroptotic activity in vitro with an EC50 of 2 nM for the RIPK1-mediated pathway. At a concentration of 1 uM for 6 hours, it selectively inhibits the expression of RIPK1 but not RIPK3 or MLKL in necrotic HT-29 cells. It effectively blocks necrosome formation by inhibiting TSZ (TNF-alpha + Smac mimetic + z-VAD-fmk)-induced phosphorylation of RIPK1, thereby preventing downstream cell death. The compound provides robust protection against TNF-alpha, cycloheximide, and z-VAD-fmk (TCZ)-induced necroptosis in a dose-dependent manner. |
| ln Vivo |
In vitro, SZM679 (10–40 mg/kg; ip; male C57BL/6 J mice with TNF-induced SIRS models) guards against TNF-induced systemic inflammatory response syndrome (SIRS) that is specific to necroptosis[1]. One daily for seven days, SZM679 (1 mg/kg) was injected intragastrically. enhances STZ-induced AD mice's cognitive function[1]. One daily for seven days, SZM679 (1 mg/kg) was injected intragastrically. reduces inflammatory cytokine expression, delays the onset of AD biomarkers, rescues brain structural damage without apparent toxicity, and prevents RIPK1 phosphorylation in AD mouse brain tissues[1].
SZM679 (1 mg/kg) administered orally once daily for 7 days improves cognitive function and rescues brain structure damage in a streptozotocin (STZ)-induced Alzheimer‘s disease (AD) mouse model. In an in vivo SIRS model, intraperitoneal injection of SZM679 (10-40 mg/kg) protects mice in a dose-dependent manner from TNF-induced systemic inflammatory response syndrome. It also decreases Tau hyperphosphorylation, neuroinflammation, and reduces RIPK1 phosphorylation levels in the hippocampus and cortex. |
| Enzyme Assay |
RIPK1 binding affinity can be measured using an enzymatic or competition binding assay. Recombinant human RIPK1 protein is incubated with increasing concentrations of SZM679 (0-1000 nM) and a tracer ligand. The binding reaction is performed in a suitable buffer for a set time. The dissociation constant (Kd) of 8.6 nM is determined via non-linear regression analysis from the binding curves generated. Selectivity over RIPK3 (Kd >5000 nM) is confirmed in parallel assays using recombinant RIPK3 protein.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: Necrotic HT-29 cells Tested Concentrations: 1 μM Incubation Duration: 6 hrs (hours) Experimental Results: Inhibited the phosphorylation of RIPK1 at 1 μM, resulting in the inhibition of the downstream phosphorylation of RIPK3 and MLKL. For the necroptosis assay, L929 or HT-29 cells are seeded in 96-well plates. Cells are treated with SZM679 (0-10 uM) for 24 hours, then stimulated with TZ (TNF-alpha + z-VAD-fmk). Cell viability is measured by the CellTiter-Glo assay or by quantifying LDH release. The EC50 value for anti-necroptosis activity is calculated as 2 nM. For the phosphorylation inhibition assay, necrotic HT-29 cells are treated with 1 uM SZM679 for 6 hours. The levels of phosphorylated RIPK1, RIPK3, and MLKL are then analyzed by Western blot to confirm pathway inhibition. |
| Animal Protocol |
Animal/Disease Models: Male C57BL/6 J mice with TNF-induced SIRS models[1]
Doses: 10, 20, and 40 mg/kg Route of Administration: intraperitoneal (ip)injection Experimental Results: Protected mice in a dose-dependent manner from hypothermia and death. Animal/Disease Models: Male C57BL/6 J mice with AD models[1] Doses: 1 mg/kg Route of Administration: Administered intragastrically (po); one time/day for 7 days Experimental Results: Improved the anxiety, behavior, and exploratory ability of AD mice. Improved the learning and memory ability of AD mice. Animal/Disease Models: Male C57BL/6 J mice with AD models[1] Doses: 1 mg/kg Route of Administration: Administered intragastrically (po); one time/day for 7 days Experimental Results: 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. In a TNF-induced SIRS model, male C57BL/6 J mice are injected with TNF (15 ug). SZM679 is administered via intraperitoneal injection at doses of 10, 20, and 40 mg/kg. The primary endpoint is protection from hypothermia and death, which is observed in a dose-dependent manner. In an STZ-induced AD model, SZM679 is administered intragastrically at 1 mg/kg once daily for 7 days. The compound's efficacy is evaluated by cognitive and behavioral tests (e.g., Morris water maze) and by biochemical analysis of brain tissue to measure Tau phosphorylation and neuroinflammation markers. |
| ADME/Pharmacokinetics |
SZM679 is orally active and bioavailable. Its molecular weight is 591.51, and it has a molecular formula of C27H18F5N3O5S. For in vivo formulations, the compound can be prepared in a solution containing 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline for injection. The powder form should be stored at -20degC for up to 3 years for long-term stability. When dissolved in DMSO, it is recommended to store at -80degC for up to 1 year. It exhibits good solubility in DMSO.
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| Toxicity/Toxicokinetics |
In a 7-day treatment study in an AD mouse model at a dose of 1 mg/kg (oral, once daily), SZM679 was reported to cause no obvious toxicity while rescuing brain structure damage. In the TNF-induced SIRS model, SZM679 protected mice from death, indicating that it is well-tolerated at active doses. No acute toxicity is reported at the tested doses. However, as a research chemical, it has not undergone full toxicological profiling and is not approved for human use.
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| References | |
| Additional Infomation |
SZM679 is a research-grade, selective RIPK1 inhibitor that has not yet been approved for clinical therapy. It is a valuable tool for studying RIPK1-dependent necroptosis in the contexts of inflammatory diseases, Alzheimer‘s disease, and sepsis. Its high selectivity for RIPK1 over RIPK3 and other kinases makes it a particularly useful chemical probe. The compound is for research use only and is not intended for human therapeutic applications.
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| Molecular Formula |
C27H18F5N3O5S
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| Molecular Weight |
591.51
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| CAS # |
3027645-52-6
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| Appearance |
Off-white to light yellow solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6906 mL | 8.4529 mL | 16.9059 mL | |
| 5 mM | 0.3381 mL | 1.6906 mL | 3.3812 mL | |
| 10 mM | 0.1691 mL | 0.8453 mL | 1.6906 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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