SZM-1209 is an orally potent and specific RIPK1 inhibitor (antagonist) with a Kd of 85 nM. SZM-1209 displays high anti-necroptosis activity (EC50=22.4 ± 8.1 nM). SZM-1209 has anti-SIRS (systemic inflammatory response syndrome) and anti-ALI (acute lung injury) effects.

Physicochemical Properties

Molecular Formula	C31H29F5N4O5S2
Molecular Weight	696.71
CAS #	2919801-86-6
Appearance	Typically exists as solid at room temperature
HS Tariff Code	2934.99.9001
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)

Biological Activity

Targets	RIPK1 85 nM (Kd) RIPK3 >10000 nM (Kd)
ln Vitro	In a dose-dependent manner, SZM-1209 inhibits necroptosis [1]. The necroptosis signal RIPK1-RIPK3-MLKL is particularly inhibited by SZM-1209 (0-1 μM, 6 h) [1].
ln Vivo	In the mTNF-α-induced systemic inflammatory response syndrome (SIRS) paradigm, SZM-1209 (25-100 mg/kg, gavage) reverses mice mortality and exhibits strong anti-inflammatory effects [1]. By lowering pulmonary edema and pathological damage, SZM-1209 (25–100 mg/kg, intraperitoneal injection) dramatically lowers ALI (acute lung injury) [1].
Cell Assay	Western Blot Analysis[1] Cell Types: HT-29 cells Tested Concentrations: 0.1, 0.5, and 1 μM Incubation Duration: 6 h Experimental Results: 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.
Animal Protocol	Animal/Disease Models: C57BL/6J mice (female, 6-8 weeks old, mTNF-α (intravenous (iv)injection)-induced SIRS model)[1] Doses: 25, 50, and 100 mg/kg Route of Administration: intragastric (po)administration Experimental Results: 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 Dramatically diminished. Animal/Disease Models: C57BL/6J mice (female, 6-8 weeks old, NNK (HY-126477) (65 mg/kg) short-term intratracheal exposure-induced ALI model)[1] Doses: 25, 50, and 100 mg/kg Route of Administration: IP Experimental Results: demonstrated 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 diminished phosphorylation of RIPK1, and also completely blocked at a high dose of 100 mg/kg in lung tissue of ALI model mice.
References	[1]. 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.

Solubility Data

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

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.4353 mL	7.1766 mL	14.3532 mL
	5 mM	0.2871 mL	1.4353 mL	2.8706 mL
	10 mM	0.1435 mL	0.7177 mL	1.4353 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.