IOX1 is the broad-spectrum inhibitor of 2OG oxygenases and its IC50 for KDM4A/KDM3A and KDM4C/KDM6B/KDM2A/KDM4E are 0.6/0.1 μM and 0.6 μM/1.6 μM/1.8 μM/2.3 μM.
The Jumonji C domain (JmjC) demethylases belong to the superfamily of FeII and 2-oxoglutarate (2OG) oxygenases. IOX1 is a potent inhibitor against a broad-spectrum of 2OG oxygenases, including non-JmjC 2OG oxygenases, with in vitro IC50 values in the micromolar range. Treatment of HeLa cells with 300μM of IOX1 led to a dose-dependent increase in H3K9me3 fluorescence intensity compared to the DMSO-treated control group. The cellular EC50 value of IOX1 in HeLa cells was 100μM. The amplified luminescent proximity homogeneous assay revealed that the IC50 value of IOX1 for the inhibition of H3K9me3 demethylation activity of isolated KDM4C was 0.6μM. The IC50 values of IOX1 for KDM4E, KDM2A, KDM3A, KDM5C, KDM6B, and PHD2 were 2.3, 1.8, 0.1, 19.0, 1.4, and 33.0μM, respectively.[3] In immunocompetent C57BL/6 mice harboring B16F10 tumors with a volume of about 50 mm3, repetitive intraperitoneal administration of IOX1 (2.5mg/kg) every two days significantly attenuated melanoma expansion at 10 days after treatment.[4]
作用机制
IOX1 is a potent, broad-spectrum 2OG oxygenase inhibitor with low cell permeability due to its polar C-5 carboxyl group.[3]
IOX1 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
HCT116 cells
Cytotoxicity assay
48 h
Cytotoxicity against human HCT116 cells assessed as cell viability after 48 hrs by MTT assay, IC50=28.1 μM
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human A549 cells
Cytotoxicity assay
48 h
Cytotoxicity against human A549 cells assessed as cell viability after 48 hrs by MTT assay, IC50=48.3 μM
26491978
human HeLa cells
Function assay
72 h
Induction of histone methylation in human HeLa cells assessed as H3K9me2 level after 72 hrs by immunofluorescence assay
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