| Identification | Back Directory | [Name]
IKE) | [CAS]
1801530-11-9 | [Synonyms]
IKE)
Ferroptosis inducer IKE
Imidazole ketone erastin
Imidazole ketone erastin
(Ferroptosis inducer IKE
IMIDAZOLE KETONE ERASTIN;FERROPTOSIS INDUCER IKE;IKE
4(3H)-Quinazolinone, 2-[[4-[2-(4-chlorophenoxy)acetyl]-1-piperazinyl]methyl]-3-[5-[2-(1H-imidazol-1-yl)acetyl]-2-(1-methylethoxy)phenyl]- | [Molecular Formula]
C35H35ClN6O5 | [MOL File]
1801530-11-9.mol | [Molecular Weight]
655.14 |
| Chemical Properties | Back Directory | [Boiling point ]
886.5±75.0 °C(Predicted) | [density ]
1.34±0.1 g/cm3(Predicted) | [storage temp. ]
Sealed in dry,2-8°C | [solubility ]
DMF: 10mg/mL,DMSO: 1mg/mL,DMSO:PBS (pH 7.2) (1:2): 0.25mg/mL | [form ]
A crystalline solid | [pka]
6.12±0.10(Predicted) | [color ]
White to yellow | [InChIKey]
PSPXJPWGVFNGQI-UHFFFAOYSA-N | [SMILES]
N1C2=C(C=CC=C2)C(=O)N(C2=CC(C(CN3C=NC=C3)=O)=CC=C2OC(C)C)C=1CN1CCN(C(COC2=CC=C(Cl)C=C2)=O)CC1 |
| Hazard Information | Back Directory | [Description]
Imidazole ketone erastin is an inducer of ferroptosis. It inhibits glutamate release in human CCF-STTG1 astrocytoma cells (IC50 = 30 nM), indicating inhibition of the system xc- cystine/glutamate transporter. Imidazole ketone erastin increases production of lipid reactive oxygen species (ROS) in SUDHL6 diffuse large B cell lymphoma (DLBCL) cells in a concentration-dependent manner, as well as reduces glutathione (GSH) levels in these cells (IC50 = 34 nM). It inhibits the growth of HT-1080 fibrosarcoma cells (GI50 = 310 nM) as well as HRASG12V-overexpressing BJeLR cells (IC50 = 3 nM). Imidazole ketone erastin (23 and 40 mg/kg) reduces tumor growth in an SUDHL6 mouse xenograft model. | [Uses]
PUN30119 is potent, metabolically stable inhibitor of system xc. | [in vivo]
IKE (23-40 mg/kg; i.p. once daily for 13 d) inhibits tumor growth in mice[1].
IKE (50 mg/kg; a single i.p) depletes GSH significantly starting from 4 h, and increases in the relative abundance of free fatty acids, phospholipids, and diacylglycerols (DAG) in mice[1].
IKE (50 mg/kg) exhibits half-life (1.82, 1.31, and 0.96 h) and Cmax (19515, 11384, and 5203 ng/mL) following different administration (i.p., i.v., and p.o. respectively) in mice[1]. | Animal Model: | Male NCG mice bearing SUDHL6 subcutaneous xenografts[1] | | Dosage: | 23, 40 mg/kg | | Administration: | I.p. injection once daily for 13 days | | Result: | Caused a significant decrease in tumor growth starting from day 9.
Had a weight loss starting from day 9.
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| Animal Model: | NOD/SCID mice (12 weeks old; ~28 g weight)[1] | | Dosage: | 50 mg/kg (Pharmacokinetic Analysis) | | Administration: | A single i.p., i.v., and p.o. administration | | Result: | I.p.: T1/2=1.82 h, Cmax=19515 ng/mL.
I.v.: T1/2=1.31 h, Cmax=11384 ng/mL.
P.o.: T1/2=0.96 h, Cmax=5203 ng/mL.
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| [storage]
Store at -20°C | [References]
[1] YAN ZHANG . Imidazole Ketone Erastin Induces Ferroptosis and Slows Tumor Growth in a Mouse Lymphoma Model[J]. Cell Chemical Biology, 2019, 26 5: Pages 623-633.e9. DOI: 10.1016/j.chembiol.2019.01.008
[2] MARIE-HELENE LARRAUFIE . Incorporation of metabolically stable ketones into a small molecule probe to increase potency and water solubility[J]. Bioorganic & Medicinal Chemistry Letters, 2015, 25 21: Pages 4787-4792. DOI: 10.1016/j.bmcl.2015.07.018
[3] ZHIPENG LI. Ribosome stalling during selenoprotein translation exposes a ferroptosis vulnerability[J]. Nature chemical biology, 2022, 18 7: 751-761. DOI: 10.1038/s41589-022-01033-3 |
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