ZB-R-55
Based on 1 Customer Validation
ZB-R-55 is an orally active and selective dual-mode RIPK1 inhibitor with RIPK1 IC50 values of 5.7 nM. ZB-R-55 occupies both the allosteric and ATP binding sites of RIPK1. ZB-R-55 inhibits necroptosis in cancer cells. ZB-R-55 can be used for the research of systemic inflammatory response syndrome and sepsis.
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- Purity : 99.39%
- CAS No.: 2416593-55-8
- 화학식: C25H23N5O3
- 분자량:441.48
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- Protocol
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
IC50 & Target
[1]|
RIPK1 5.7 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| U-937 | IC50 |
0.34 nM
Compound: 16; ZB-R-55
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Anti-necroptotic activity in human U-937 cells assessed as inhibition of LPS/Z-VAD-fmk induced necroptosis
Anti-necroptotic activity in human U-937 cells assessed as inhibition of LPS/Z-VAD-fmk induced necroptosis
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[PMID: 36781172] |
| U-937 | IC50 |
0.34 nM
Compound: ZB-R-55; 66
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Anti-necrotic activity in human U-937 cells
Anti-necrotic activity in human U-937 cells
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[PMID: 36346971] |
In Vitro
ZB-R-55 (Compound 21) potently inhibits purified RIPK1 kinase activity with an IC50 of 5.7 nM[1].
ZB-R-55 potently inhibits TSZ-induced necroptosis in U937 cells with an IC50 of 0.34 nM[1].
ZB-R-55 (0.0001-1 μM) potently inhibits purified RIPK1 kinase activity in a 33P-radiolabeled assay with an IC50 of 16 nM[1].
ZB-R-55 (1 μM) shows complete selectivity for RIPK1 over 465 other tested human kinases when assayed in a KINOMEscan competition binding assay[1].
ZB-R-55 binds to the RIPK1 kinase domain in a dual-mode manner, occupying both the allosteric and ATP-binding pockets to form multiple hydrophobic and hydrogen bond interactions with key residues[1].
ZB-R-55 (3 h) specifically binds to RIPK1 (but not RIPK3 or MLKL) in HT-29 cell lysates[3].
ZB-R-55 (0.01-1 μM; 24 h) has minimal impact on RIPK1 protein levels in HT-29 cells when treated at concentrations of 0.01 to 1 μM for 24 h[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:HT-29 cells
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Concentration:0.01 μM; 0.03 μM; 0.1 μM; 0.3 μM; 1 μM
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Incubation Time:24 h
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Result:Resulted in minimal reduction of RIPK1 protein levels across all tested concentrations, in contrast to the robust RIPK1 degradation induced by the PROTAC MS2031 at the same concentrations.
Parmacokinetics
In Vivo
ZB-R-55 (10 mg/kg; p.o.; single dose) significantly attenuates the production of TNFα and IL-6/12 in mice in a LPS (HY-D1056)-induced sepsis model[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Mice (female; 6-8 wekks old; intravenously injected with TNFα for a lethal shock model)[1]
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Dosage:10 mg/kg
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Administration:p.o.; single dose
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Result:Exhibited strong protection from hypothermia.
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Animal Model:Mice (female; 6-8 wekks old; intravenously injected with LPS for a sepsis model)[1]
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Dosage:10 mg/kg
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Administration:p.o.; single dose
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Result:Showed strong protection from hypothermia.
Attenuated the production of TNFα and IL-6/12.
Chemical Information
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CAS No. 2416593-55-8
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Appearance Solid
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분자량 441.48
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화학식 C25H23N5O3
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Color White to off-white
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SMILES
CN1C2=CC(C#CC3CC3)=CC=C2OC[C@H](NC(C4=NC(CC5=CC=CC=C5)=NN4)=O)C1=O
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
용액&용해도
In Vitro:
DMSO : 100 mg/mL (226.51 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.66 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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LPS-Induced Endotoxemia/Systemic Inflammation
Lipopolysaccharide (LPS)-induced endotoxemia is a widely used in vivo model of acute systemic inflammation in which LPS, a Gram-negative bacterial endotoxin, activates innate immune signaling primarily through TLR4, leading to rapid and transient induction of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β in circulation and tissues. This cytokine surge is commonly used as a measurable readout of systemic inflammatory activation and immune dysregulation, and is typically assessed within hours after intraperitoneal LPS administration in mouse models of endotoxemia. The model captures key features of systemic inflammatory response syndrome, including cytokine release, immune cell activation, and downstream tissue responses, and has been used to evaluate anti-inflammatory interventions such as cytokine modulation, lipid mediators, and immune cell-targeting therapies.
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Research Protocol for Inflammation-related Diseases
The NLRP3 inflammasome is a cytosolic innate immune signaling platform that integrates priming signals and danger-signal activation to promote caspase-1 activation, maturation of IL-1β and IL-18, and gasdermin D-mediated pyroptotic cell death. The core experimental logic is to determine whether inflammatory disease phenotypes are driven by increased NLRP3 expression, ASC-containing inflammasome assembly, caspase-1 cleavage, GSDMD cleavage, and extracellular release of IL-1β/IL-18 rather than by nonspecific cell injury alone. The pathway is strongly linked to inflammation-related disease phenotypes because monosodium urate crystals activate NALP3/NLRP3 inflammasome signaling in gout-like crystal inflammation, cholesterol crystals activate NLRP3 inflammasomes in atherogenesis models, and DSS-induced intestinal inflammation has been reported to involve NLRP3 inflammasome activity. However, experimental colitis studies also show context-dependent protective effects of NLRP3 inflammasome co
순도&문서
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Data Sheet (276 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Handling Instructions (2659 KB)
References
[1]. Yang X, et al. Potent and Selective RIPK1 Inhibitors Targeting Dual-Pockets for the Treatment of Systemic Inflammatory Response Syndrome and Sepsis. Angew Chem Int Ed Engl. 2022;61(5):e202114922. [Content Brief]
[2]. Zhou Y, et al. Necroptosis inhibitors: mechanisms of action and therapeutic potential. Apoptosis. 2024;29(1-2):22-44. [Content Brief]
[3]. Inuzuka H, et al. Targeted Degradation of Receptor-Interacting Protein Kinase 1 to Modulate the Necroptosis Pathway. ACS Pharmacol Transl Sci. 2024;7(11):3518-3526. Published 2024 Oct 15. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 2.2651 mL | 11.3255 mL | 22.6511 mL | 56.6277 mL |
| 5 mM | 0.4530 mL | 2.2651 mL | 4.5302 mL | 11.3255 mL | |
| 10 mM | 0.2265 mL | 1.1326 mL | 2.2651 mL | 5.6628 mL | |
| 15 mM | 0.1510 mL | 0.7550 mL | 1.5101 mL | 3.7752 mL | |
| 20 mM | 0.1133 mL | 0.5663 mL | 1.1326 mL | 2.8314 mL | |
| 25 mM | 0.0906 mL | 0.4530 mL | 0.9060 mL | 2.2651 mL | |
| 30 mM | 0.0755 mL | 0.3775 mL | 0.7550 mL | 1.8876 mL | |
| 40 mM | 0.0566 mL | 0.2831 mL | 0.5663 mL | 1.4157 mL | |
| 50 mM | 0.0453 mL | 0.2265 mL | 0.4530 mL | 1.1326 mL | |
| 60 mM | 0.0378 mL | 0.1888 mL | 0.3775 mL | 0.9438 mL | |
| 80 mM | 0.0283 mL | 0.1416 mL | 0.2831 mL | 0.7078 mL | |
| 100 mM | 0.0227 mL | 0.1133 mL | 0.2265 mL | 0.5663 mL |
ZB-R-55 Related Classifications
HY-161059 Related Classifications
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