RIP1-IN-1
RIP1-IN-1 is an orally active RIP1 inhibitor with strong RIP1 binding affinity (Kd: 110 nM). RIP1-IN-1 exhibits strong anti-necroptosis activity. RIP1-IN-1 effectively inhibits the formation of necrosomes by blocking the phosphorylation of RIP1, RIP3 and MLKL signaling pathways. RIP1-IN-1 inhibits necroptosis and can be used in the study of acute liver injury.
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- Formule: C26H21N3O3
- Masse moléculaire:423.46
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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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Activité biologique
Description
IC50 & Target
[1]|
RIPK1 110 nM (Kd) |
In Vitro
RIP1-IN-1 (Compound N-1) (0-1.6 μM, 5-24 h) can effectively and dose-dependently inhibit Z-VAD-FMK (HY-16658B) induced necroptosis in HT-29 cells, as well as Z-VAD-FMK (HY-16658B) induced necroptosis in U937 cells[1].
RIP1-IN-1 exhibits strong anti-necroptosis activity in HT-29 cells (CC50: >50 μM EC50: 8.8 nM)[1].
RIP1-IN-1 (0.4 μM, 2-6 h) effectively prevents the phosphorylation of both RIP1 and RIP3 in HT-29 cells treated with Z-VAD-FMK (HY-16658B) in a time-dependent manner, thereby inhibiting the phosphorylation of the downstream target MLKL[1].
RIP1-IN-1 (0.097-400 nM, 5 h) inhibits RIP1/3 and MLKL phosphorylation in a dose-responsive manner[1].
RIP1-IN-1 (400 nM, 6 h) inhibits Z-VAD-FMK (HY-16658B) induced necrosome formation in HT-29 cells by blocking phosphorylation of the RIP1/RIP3/MLKL pathway, demonstrating its anti-necroptosis activity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Z-VAD-FMK (30 μM) treated HT-29 cells
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Concentration:0.097、1.562、25、400 nM
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Incubation Time:2-6 h
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Result:Prevented the phosphorylation of both RIP1 and RIP3 within 2-6 h and subsequently inhibited downstream target MLKL phosphorylation.
Reduced pRIP1, pRIP3, and pMLKL levels in a dose-dependent manner in the range of 0.097-400 nM.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Plasma Concentration | MRT | Clearance (CL) | Vd | AUC | Bioavailability |
|---|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 10 mg/kg | i.g. | 0.82 h | 0.5 h | 726 ng/mL | 1.65 h | 116 mL/min/kg | 8.29 L/kg | 1.442 μg·h/mL | 26.3 % |
In Vivo
RIP1-IN-1 (3 mg/kg, i.g. once a day for 14 consecutive days) shows protective effect in the CCl4-induced acute liver injury model in mice[1].
RIP1-IN-1 (10 mg/kg, i.g.) shows short half-life and high clearance in Sprague-Dawley rats[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 mice; Establishment of SIRS mice model by combining mTNF-α (65 μg/kg) and Z-VAD-FMK (200 μg/piece)[1]
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Dosage:1, 3, 5 mg/kg (5 % DMSO and 95 % CMC-Na solution)
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Administration:p.o.
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Result:Significantly improved the survival rate of SIRS mice, reaching 20%, 50% and 90%.
Alleviated mTNF-α-induced hypothermia within 9 hours.
Significantly reduced serum IL-6 levels, indicating its anti-inflammatory effect.
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Animal Model:Male ICR mice (6-8 weeks old), 0.01 % CCl4 induced acute liver injury mice model[1]
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Dosage:1, 3, 5 mg/kg (5 % DMSO and 95 % CMC-Na solution)
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Administration:i.g., once daily for 14 consecutive days
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Result:Significantly reduced RIP1, RIP3, and MLKL phosphorylation in diseased mice, thereby restoring AST and ALT markers indicative of liver damage.
HE staining showed that the liver tissue structure was close to normal at a dose of 3mg/kg and 5mg/kg, and the damage was significantly reduced.
The result showed that ALT, AST, and IL-6 levels were significantly reduced and close to the normal range, indicating that it can play a protective role against acute liver damage.
Western Blot results showed that it can effectively inhibit phosphorylation and block the necroptosis pathway.
Chemical Information
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Masse moléculaire 423.46
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Formule C26H21N3O3
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SMILES
CN1C2=CC=CC=C2OC[C@H](NC(C3=CC(C(C4=CC=CC=C4)=CC=N5)=C5C=C3)=O)C1=O
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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)
RIP1-IN-1 Related Classifications
HY-173185 Related Classifications
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