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JKE-1674

Names

[ CAS No. ]:
2421119-60-8

[ Name ]:
JKE-1674

[Synonym ]:
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

Biological Activity

[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.

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
595.5±60.0 °C at 760 mmHg

[ Molecular Formula ]:
C20H20Cl2N4O4

[ Molecular Weight ]:
451.303

[ Flash Point ]:
313.9±32.9 °C

[ Exact Mass ]:
450.086151

[ LogP ]:
3.35

[ Vapour Pressure ]:
0.0±1.8 mmHg at 25°C

[ Index of Refraction ]:
1.651

Related Compounds