RIPA-56 |
Catalog No.GC31652
One-Click Copy Product Info
|
A RIPK1 inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1956370-21-0
Sample solution is provided at 25 µL, 10mM.
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RIPA-56 is a highly potent, selective, and metabolically stable inhibitor of receptor-interacting protein 1 (RIP1) with an IC50 of 13 nM.
RIPA-56 has a half-life of 128 min in human liver microsomal stability assays and an EC50 of 28 nM in TSZ-induced HT-29 necrosis assay. RIPA-56 also demonstrates potency in protection of murine L929 cells from TZ-induced necrosis (EC50=27 nM). RIPA-56 shows efficient inhibition of RIP1 kinase activity, with an IC50 of 13 nM and no inhibition of RIP3 kinase activity at a 10 μM concentration. RIPA-56 could form tight hydrophobic interactions with RIP1 through both the phenyl group and the 2,2-dimethylbutyl group, and form two important hydrogen bonds[1].
In the SIRS mice disease model, RIPA-56 efficiently reduces tumor necrosis factor alpha (TNFα)-induced mortality and multi-organ damage. Compared to known RIP1 inhibitors, RIPA-56 is potent in both human and murine cells, is much more stable in vivo, and is efficacious in animal model studies. RIPA-56 has an impressive PK profile in mice with a 3.1 h half-life, 22% oral bioavailability (P.O.), and 100% bioavailability from intraperitoneal injection (I.P.)[1].
[1]. Ren Y, et al. Discovery of a Highly Potent, Selective, and Metabolically Stable Inhibitor of Receptor-InteractingProtein 1 (RIP1) for the Treatment of Systemic Inflammatory Response Syndrome. J Med Chem. 2017 Feb 9;60(3):972-986.
Cell experiment: | Cell necrosis assay is performed in 96-well cell culture plate. 3,000 cells are plated in each well and cultured at 37°C overnight. HT-29 cells are treated with 20 ng/mL TNFα/100 nM Smac Mimetics/20 μM z-VAD-FMK and RIPA-56 for 24 h. L929 cells are treated with 20 ng/mL TNFα/20 μM z-VAD-FMK and RIPA-56 for 6 h. The cell survival ratio is determined using the Cell Titer-Glo Luminescent Cell Viability Assay kit[1]. |
Animal experiment: | Mice: Following intraveneous (IV), intraperitoneal (IP), or oral administration (PO) of RIPA-56 to C57BL/6 mice (n=3), blood is sampled through eye puncture at various time points. Compound concentrations in the plasma samples are analyzed by LCMS/MS. Pharmacokinetic parameters are determined from individual animal data using noncompartmental analysis in phoenix 64[1]. |
References: [1]. Ren Y, et al. Discovery of a Highly Potent, Selective, and Metabolically Stable Inhibitor of Receptor-InteractingProtein 1 (RIP1) for the Treatment of Systemic Inflammatory Response Syndrome. J Med Chem. 2017 Feb 9;60(3):972-986. | |
| Cas No. | 1956370-21-0 | SDF | |
| Canonical SMILES | CCC(C)(C)C(N(CC1=CC=CC=C1)O)=O | ||
| Formula | C13H19NO2 | M.Wt | 221.3 |
| Solubility | DMSO : ≥ 100 mg/mL (451.88 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 4.5188 mL | 22.5938 mL | 45.1875 mL |
| 5 mM | 903.8 μL | 4.5188 mL | 9.0375 mL |
| 10 mM | 451.9 μL | 2.2594 mL | 4.5188 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 32 reference(s) in Google Scholar.)