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].
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 .
JKE-1674 (50mg/kg; p.o.) can be detected in the serum of mice dosed orally with the compound[1].
| Animal Model: | SCID mice[1] |
| Dosage: | 50mg/kg (Pharmacokinetic Analysis) |
| Administration: | P.o. |
| Result: | Could be detected in the serum of mice dosed orally with the compound.
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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)
