| Chemical Properties | Back Directory | [Boiling point ]
595.5±60.0 °C(Predicted) | [density ]
1.43±0.1 g/cm3(Predicted) | [storage temp. ]
4°C, protect from light | [solubility ]
DMSO: soluble | [form ]
A crystalline solid | [pka]
6.67±0.58(Predicted) | [color ]
Off-white to light yellow | [InChI]
InChI=1S/C20H20Cl2N4O4/c21-16-5-1-14(2-6-16)19(15-3-7-17(22)8-4-15)24-9-11-25(12-10-24)20(27)18(23-28)13-26(29)30/h1-8,19,28H,9-13H2 | [InChIKey]
XIOHKIAPXVDWCP-UHFFFAOYSA-N | [SMILES]
C(N1CCN(C(C2=CC=C(Cl)C=C2)C2=CC=C(Cl)C=C2)CC1)(=O)C(=NO)C[N+]([O-])=O |
| Hazard Information | Back Directory | [Uses]
JKE-1674 is an orally active glutathione peroxidase 4 (GPX4) inhibitor and an active metabolite of GPX4 inhibitor ML-210. JKE-1674, an analog of ML-210 in which the nitroisoxazole ring is replaced with an α-nitroketoxime. JKE-1674 can convert into a nitrile oxide JKE-1777. JKE-1674 kills LOX-IMVI cells in a manner that is equipotent to ML-210 and is completely rescued by ferroptosis inhibitors[1][2][3]. | [Biological Activity]
JKE-1674 is an inhibitor of glutathione peroxidase 4 (GPX4) and an active metabolite of the GPX4 inhibitor ML-210 .1 JKE-1674 reduces viability of LOX-IMVI cancer cells (EC50 = 0.03 μM) and in a panel of additional cancer cell lines, an effect that can be blocked by the ferroptosis inhibitor ferrostatin-1 . | [in vivo]
JKE-1674 (50?mg/kg; p.o.) can be detected in the serum of mice dosed orally with the compound[1]. | Animal Model: | SCID mice[1] | | Dosage: | 50?mg/kg (Pharmacokinetic Analysis) | | Administration: | P.o. | | Result: | Could be detected in the serum of mice dosed orally with the compound.
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| [References]
1.Eaton, J.K., Furst, L., Ruberto, R.A., et al.Selective covalent targeting of GPX4 using masked nitrile-oxide electrophilesNat. Chem. Biol.16(5)497-506(2020)
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