RIPK1-IN-34
RIPK1-IN-34 is a selective, brain-penetrant RIPK1 inhibitor (IC50 = 126.70 nM) with almost no inhibitory effect on RIPK3 (IC50 ＞ 10, 000 nM). RIPK1-IN-34 offers substantial neuroprotection by inhibiting the phosphorylation of RIPK1, RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL) within the necroptosis pathway. RIPK1-IN-34 shows the neuroprotective effect in a rat middle cerebral artery occlusion (MCAO) model. RIPK1-IN-34 can be used for the study of anti-acute ischemic stroke (AIS).
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- CAS No.: 3065634-19-4
- Formule: C28H25N7O2
- Masse moléculaire:491.54
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
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Activité biologique
Description
IC50 & Target
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RIPK1 126.7 nM (IC50) |
In Vitro
RIPK1-IN-34 (Compound 9b) significantly reduces TNF-α (T), a Smac-mimetic, SM-164 (HY-15989) (S), and Z-VAD-FMK (HY-16658B) (Z)-induced apoptosis in HT-29 (EC50 = 71.61 nM) and HT-22 (EC50 = 38.45 nM) cells[1].
RIPK1-IN-34 (0.78-400 nM, 24 h) effectively counters the TSZ-induced changes and approximates the untreated control group's condition in HT-29, U937, L929 and HT-22 cells[1].
RIPK1-IN-34 (1, 10, 100 nM, 4.5 h) is effective in protecting the cells from necroptosis in L929 cells[1].
Compound RIPK1-IN-34 (0-1000 nM, 4.5 h) dose-dependently inhibits the phosphorylation of RIPK1, RIPK3, and MLKL in L929 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:L929 cells
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Concentration:1 nM, 10 nM, 100 nM
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Incubation Time:After pre-incubation with the compound for 30 minutes, cells were treated with TSZ for 4 hours
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Result:Effectively protected the cells from necroptosis in L929 cells.
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Cell Line:L929 cells
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Concentration:0 nM, 10 nM, 100 nM, 1000 nM
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Incubation Time:After pre-incubation with the compound for 30 minutes, cells were treated with TSZ for 4 hours
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Result:Decreased the intensities of p-RIPK1 and p-RIPK3 bands in response to increasing concentrations.
Curtailed the enhancement of MLKL phosphorylation.
Parmacokinetics
| Species | Dose | Route | Cmax | T1/2 | AUC0-inf | CL | Tmax | F |
|---|---|---|---|---|---|---|---|---|
| Rat | 0.5 mg/kg | i.v. | 462.6 ng/mL | 6.4 h | 2065.1 ng·h/mL | 4 mL/min/kg | / | / |
| Rat | 20 mg/kg | p.o. | 1221.2 ng/mL | 8 h | 12316.1 ng·h/mL | 27.1 mL/min/kg | 2 h | 14.9 % |
In Vivo
RIPK1-IN-34 (78.4-160 mg/kg, i.p., two intraperitoneal injections, one hour apart) does not cause acute toxicity at the dose tested in C57BL/6 mice, and its LD50 exceeds 160 mg/kg, indicating that it has a high safety profile[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SPF grade male SD rats (180-200 g) were used to construct a middle cerebral occlusion model[1].
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Dosage:0.5 mg/kg, 1.5 mg/kg, 4.5 mg/kg
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Administration:I.v., administered intravenously once 0.5 hours before modeling, and again after reperfusion, for a total of two administrations
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Result:Significantly improved neurological outcomes 24 h post-operation, with reductions in scores exhibiting a dose-dependent trend: low dose (5.20), medium dose (5.09), and high dose (3.82).
Significantly reduced infarct volumes across all treatment groups in a dose-responsive manner: low dose (20.60), medium dose (18.32), and high dose (16.51).
Diminished MDA, TNF-α, and IL-1β levels while slightly increasing SOD levels.
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Animal Model:SPF grade male C57BL/6 mice (aged 6-8 weeks, weighing 18-22 g)[1].
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Dosage:160 mg/kg, 112 mg/kg, 78.4 mg/kg
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Administration:I.p., two intraperitoneal injections, one hour apart
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Result:No abnormal behaviors or deaths were observed, and the body weight of mice in all groups steadily increased over 7 days with no significant differences.
Chemical Information
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CAS No. 3065634-19-4
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Masse moléculaire 491.54
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Formule C28H25N7O2
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SMILES
O=C(C1=C2C=C(C3=CC4=NC(NC(C5CC5)=O)=NN4C=C3)C=CC2=NC(C)=N1)N[C@H](C6=CC=CC=C6)C
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
RIPK1-IN-34 Related Classifications
HY-178464 Related Classifications
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