| Field | Specification |
|---|---|
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C13H19NO2 |
| Purity | |
| SMILES | |
| Form | Solid |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
RIPA-56 is a highly potent, selective, metabolically stable inhibitor of receptor-interacting protein 1 (RIP1), with an IC50 of 13 nM. It can be applied in the treatment of systemic inflammatory response syndrome[1]. It is supplied as a white to off-white solid (C13H19NO2, MW 221.30) at 99.94% purity.
Physical & Chemical Properties
| CAS Number | 1956370-21-0 |
|---|---|
| Molecular Formula | C13H19NO2 |
| Molecular Weight | 221.30 g/mol |
| Purity | 99.94% |
| Appearance | Solid |
| Color | White to off-white |
| SMILES | CCC(C)(C)C(N(CC1=CC=CC=C1)O)=O |
| Signaling Pathway | Apoptosis |
| Solubility | In Vitro: DMSO: ≥ 100 mg/mL (451.88 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) * "≥" means soluble, but saturation unknown. |
| Storage | Powder: -20°C, 3 years; 4°C, 2 years. In solvent: -80°C, 2 years; -20°C, 1 year. |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Biological Activity
IC50 & Target
IC50: 13 nM (RIP1)[1]
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 | ≥ 100 mg/mL (451.88 mM) | use freshly opened DMSO (absorbed moisture lowers solubility) |
Aliquot the stock solution and store it at -80°C (up to 2 years) or -20°C (up to 1 year); avoid repeated freeze-thaw cycles.
In Vivo
Choose the formulation that suits the animal model and route of administration; percentages are volume ratios of the final working solution. Start from a clear DMSO stock (see In Vitro above), add the co-solvents one at a time in the order listed, mixing after each addition, and prepare the working solution fresh on the day of dosing. If precipitation or phase separation occurs, gentle warming or sonication can help.
Protocol 1
| Composition | 5% DMSO + 40% PEG300 + 5% Tween-80 + 50% saline |
|---|---|
| Result | ≥ 2.75 mg/mL (12.43 mM); clear solution |
Protocol 2
| Composition | 5% DMSO + 95% (20% SBE-β-CD in saline) |
|---|---|
| Result | ≥ 2.75 mg/mL (12.43 mM); clear solution |
Protocol 3
| Composition | 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline |
|---|---|
| Result | ≥ 2.5 mg/mL (11.30 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 2.5 mg/mL (saturation not determined). For 1 mL of working solution: add 100 μL DMSO stock (25.0 mg/mL) to 400 μL PEG300; then 50 μL Tween-80; then 450 μL saline to bring the volume to 1 mL. Saline: dissolve 0.9 g sodium chloride in ddH2O and make up to 100 mL. |
Protocol 4
| Composition | 10% DMSO + 90% (20% SBE-β-CD in saline) |
|---|---|
| Result | ≥ 2.5 mg/mL (11.30 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 2.5 mg/mL (saturation not determined). For 1 mL of working solution: add 100 μL DMSO stock (25.0 mg/mL) to 900 μL 20% SBE-β-CD in saline. 20% SBE-β-CD in saline: dissolve 2 g SBE-β-CD powder in 10 mL saline until clear (4°C, store up to one week). |
Protocol 5
| Composition | 10% DMSO + 90% Corn Oil |
|---|---|
| Result | ≥ 2.5 mg/mL (11.30 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 2.5 mg/mL (saturation not determined). Use with caution if continuous dosing will exceed two weeks. For 1 mL of working solution: add 100 μL DMSO stock (25.0 mg/mL) to 900 μL corn oil. |
Data provided by the manufacturer.
In Vitro
RIPA-56 efficiently inhibits RIP1 kinase activity, with an IC50 of 13 nM, and does not inhibit RIP3 kinase activity at 10 μM. RIPA-56 also protects murine L929 cells from TNFα/z-VAD-FMK (TZ)-induced necrosis (EC50=27 nM)[1].
In Vivo
In the SIRS mouse disease model, RIPA-56 efficiently reduces mortality and multi-organ damage induced by tumor necrosis factor alpha (TNFα). Compared with known RIP1 inhibitors, RIPA-56 shows potency in human as well as murine cells, is far more stable in vivo, and efficacious in animal model studies. In mice, RIPA-56 has an impressive PK profile: half-life of 3.1 h, oral (P.O.) bioavailability of 22%, and 100% bioavailability after intraperitoneal injection (I.P.)[1].
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
Cell Assay[1]
Run the cell necrosis assay in 96-well cell culture plates. Plate 3,000 cells per well and culture at 37°C overnight. For HT-29 cells, apply 20 ng/mL TNFα/100 nM Smac Mimetics/20 μM z-VAD-FMK together with RIPA-56 for 24 h. Treat L929 cells with 20 ng/mL TNFα/20 μM z-VAD-FMK and RIPA-56 for 6 h. Determine the cell survival ratio with the Cell Titer-Glo Luminescent Cell Viability Assay kit[1].
Animal Administration[1]
Mice: Administer RIPA-56 to C57BL/6 mice (n=3) intravenously (IV), intraperitoneally (IP), or orally (PO), and sample blood through eye puncture at various time points. Analyze compound concentrations in the plasma samples by LCMS/MS. Determine pharmacokinetic parameters from individual animal data by noncompartmental analysis in phoenix 64[1].
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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Patent. US20220362179A1.
