2421119-60-8

2421119-60-8 structure

Name: JKE-1674
Chemical Name: JKE-1674
CAS Number: 2421119-60-8
Molecular Formula: C₂₀H₂₀Cl₂N₄O₄
Molecular Weight: 451.303
Catalog: Signaling Pathways Apoptosis Ferroptosis
Create Date: 2021-08-15 18:02:45
Modify Date: 2024-01-10 14:24:06
JKE-1674 is an orally active glutathione peroxidase 4 (GPX4) inhibitor. JKE-1674 kills cells in a manner that is equipotent to ML210 and is completely rescued by ferroptosis inhibitors[1].

Name	JKE-1674
Synonyms	1,2-Propanedione, 1-[4-[bis(4-chlorophenyl)methyl]-1-piperazinyl]-3-nitro-, 2-oxime, (2E)- (2E)-1-{4-[Bis(4-chlorophenyl)methyl]-1-piperazinyl}-2-(hydroxyimino)-3-nitro-1-propanone JKE-1674

Description	JKE-1674 is an orally active glutathione peroxidase 4 (GPX4) inhibitor. JKE-1674 kills cells in a manner that is equipotent to ML210 and is completely rescued by ferroptosis inhibitors[1].
Related Catalog	Research Areas >> Cancer Signaling Pathways >> Apoptosis >> Ferroptosis
Target	GPX4[1]
In Vitro	JKE-1674 exhibits activity indistinguishable from that of ML210 in cellular target engagement assays including yielding the same +434Da GPX4 adduct in cells. JKE-1674 kills cells in a manner that is equipotent to ML210 and is completely rescued by ferroptosis inhibitors. JKE-1674 forms a nitrile-oxide electrophile in cells. JKE-1674 dehydration yields a nitrile-oxide electrophile that binds GPX4. JKE-1674 exhibits far greater stability than chloroacetamide inhibitors[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.
References	[1]. Eaton JK, et al. Selective covalent targeting of GPX4 using masked nitrile-oxide electrophiles. Nat Chem Biol. 2020;16(5):497-506.