Zharp1-163
Zharp1-163 is a dual inhibitor of ferroptosis and necroptosis. Zharp1-163 effectively blocks ferroptosis by reducing reactive oxygen species (ROS) levels and inhibits necroptosis by potently and selectively targeting RIPK1 kinase activity (KD = 240 nM; IC50 = 406.1 nM). Zharp1-163 inhibits the cellular activation of RIPK1, RIPK3 and MLKL in response to necroptotic stimulation. Zharp1-163 markedly attenuates TNF-α (HY-P1875)-induced systemic inflammatory syndrome, including the prevention of TNF-α-induced mortality and hypothermia in mice. Zharp1-163 significantly alleviates acute kidney injury associated with both necroptosis and ferroptosis in models induced by Cisplatin (HY-17394) and ischemia-reperfusion. Zharp1-163 can be used for the study of diseases associated with cell death pathways, such as kidney disease.
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Formule: C21H23N5O3
- Masse moléculaire:393.44
-
Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Activité biologique
-
Chemical Information
- Pureté et documentation
- Références
-
Help & FAQs
Activité biologique
|
RIPK1 240 nM (Kd) |
RIPK1 406.1 nM (IC50) |
RIPK3 |
Zharp1-163 (0.01-10μM, 18 h) significantly inhibits Erastin (HY-15763)-or RSL3 (HY-100218A)-induced ferroptosis in HT-1080 cells (EC50 = 0.95 μM; EC50 = 1.33 μM) and Mouse Embryonic Fibroblasts (MEFs) (EC50 = 1.93 μM; EC50 = 1.39 μM)[1].
Zharp1-163 (0.01-10 μM, 14-18 h) blocks TNF-α, Smac mimetic, and Z-VAD (HY-164388)-induced necroptosis in HT-29 cells (EC50 = 0.1 μM), and MEFs (EC50 = 0.11 μM)[1].
Zharp1-163 (0.01-10 μM, 14 h) efficiently inhibits TNFα and Z-VAD-induced necroptosis in mouse fibroblast L929 cells[1].
Zharp1-163 (0.3-3 μM, 26 h) inhibits apoptosis induced by TNFα plus Smac mimetic in MEFs[1].
Zharp1-163 (0.3-3 μM, 8 h) does not affect pyroptosis in THP-1 cells[1].
Zharp1-163 (10 μM, 7 h) significantly reduces lipid ROS production during ferroptosis and reduces the induction of both CHAC1 and PTGS2 induced by RSL3 in HT-1080 cells[1].
Zharp1-163 (0.1-3 μM, 10 h) eliminates the phosphorylation of RIPK1, RIPK3, and MLKL in human HT-29 cells and blocks the phosphorylation of RIPK1, RIPK3, and MLKL in MEFs[1].
Zharp1-163 (0.3-3 μM, 10 h) prevents both the generation of RIPK3 puncta and MLKL oligomerization in HT-29 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:HT-1080 cells and MEFs.
-
Concentration:0.01 μM, 0.1 μM, 1 μM, 10 μM
-
Incubation Time:Pretreated 2 h and then treated with Erastin or RSL3 for 16 h
-
Result:Significantly inhibited Erastin- or RSL3-induced ferroptosis in HT-1080 cells and MEFs.
-
Cell Line:HT-1080 cells and MEFs.
-
Concentration:0.01 μM, 0.1 μM, 1 μM
-
Incubation Time:Pretreated 2 h, followed by treatment with TNF-α (T) (40 ng/mL), Smac mimetic (S) (100 nM), Z-VAD (Z) (20 μM) for 12-16 h
-
Result:Blocked TNF-α, Smac mimetic, and Z-VAD-induced necroptosis in HT-29 cells (EC50 = 0.1 μM), in MEFs (EC50 = 0.11 μM).
-
Cell Line:Mouse fibroblast L929 cells
-
Concentration:0.01 μM, 0.1 μM, 1 μM
-
Incubation Time:2 h, followed by treatment with T (40 ng/mL) and Z (20 μM) for 12 h
-
Result:Blocked TNF-α, Z-VAD-induced necroptosis in mouse fibroblast L929 cells (EC50 = 0.08 μM).
-
Cell Line:MEFs
-
Concentration:0.3 μM, 1 μM, 3 μM
-
Incubation Time:2 h before treatment with T (40 ng/mL) and S (100 nM) for 24 h
-
Result:Inhibited apoptosis induced by TNFα plus Smac mimetic in MEFs.
-
Cell Line:HT-1080 cells
-
Concentration:10 μM
-
Incubation Time:2 h, followed by induction with RSL3 for 5 h
-
Result:Significantly reduced the induction of both CHAC1 and PTGS2 in response to RSL3.
-
Cell Line:HT-29 cells, MEFs
-
Concentration:0.1 μM, 0.3 μM, 1 μM, 3 μM
-
Incubation Time:2 h, followed by treatment with T (40 ng/mL), S (100 nM) and Z (20 μM) for 8 h
-
Result:Eliminated the phosphorylation of RIPK1, RIPK3, and MLKL in human HT-29 cells.
Blocked the phosphorylation of RIPK1, RIPK3, and MLKL in MEFs.
-
Cell Line:HT-29 cells stably expressing Flag-tagged RIPK3
-
Concentration:0.3 μM, 1 μM, 3 μM
-
Incubation Time:Before the addition of T (40 ng/mL), S (100 nM), and Z (20 μM) for an additional 8 h, HT-29 cells stably expressing Flag-tagged RIPK3 were preincubated with the specified compounds for 2 h
-
Result:Prevented the generation of RIPK3 puncta.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:C57BL/6 mice injected TNF[1].
-
Dosage:5 mg/kg
-
Administration:I.p., pretreated with 30 min prior to challenge
-
Result:Significantly protected mice from TNF-α-induced lethality and reduced TNF-α-induced temperature loss in these mice.
Significantly ameliorated the production of proinflammatory cytokines, including IL-6.
Induced damage to the cecum and colon.
-
Animal Model:Cisplatin-induced acute kidney injury in C57BL/6 mice[1].
-
Dosage:5 mg/kg
-
Administration:I.p., pretreated with 30 min prior to challenge
-
Result:Significantly inhibited cisplatin-induced body weight loss.
Mitigated mild inflammation and tubular epithelial cell damage.
Decreased the serum creatinine and blood urea nitrogen (BUN) levels in the context of Cisplatin-induced kidney injury.
-
Animal Model:The left renal artery of C57BL/6 mice pretreated for 2 h was isolated and clamped for 45 min via a nontraumatic artery clamp following right nephrectomy. Reperfusion was subsequently performed[1].
-
Dosage:5 mg/kg
-
Administration:I.p., 2 h
-
Result:Significantly inhibited the levels of creatinine and BUN in mouse serum.
Chemical Information
-
Masse moléculaire 393.44
-
Formule C21H23N5O3
-
SMILES
NC1=CN2C(C=CC(C3=CC4=C(N=C3)OCCN4C(OC5CCCCC5)=O)=C2)=N1
-
Livraison
Room temperature in continental US; may vary elsewhere.
-
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)
Zharp1-163 Related Classifications
HY-178163 Related Classifications
Powered by Bioz