|S7070||GSK J4 HCl||90 mg/mL||90 mg/mL||90 mg/mL|
|S7281||JIB-04||<1 mg/mL||25 mg/mL||<1 mg/mL|
|S7296||ML324||<1 mg/mL||43 mg/mL||3 mg/mL|
|S7234||IOX1||<1 mg/mL||37 mg/mL||<1 mg/mL|
|S7581||GSK J1||<1 mg/mL||77 mg/mL||<1 mg/mL|
|S4800||Daminozide||-1 mg/mL||32 mg/mL||-1 mg/mL|
|S7796||GSK2879552 2HCl||44 mg/mL||29 mg/mL||<1 mg/mL|
|S8601||CP2||100 mg/mL||-1 mg/mL||-1 mg/mL|
GSK J4 HCl is a cell permeable prodrug of GSK J1, which is the first selective inhibitor of the H3K27 histone demethylase JMJD3 and UTX with IC50 of 60 nM in a cell-free assay and inactive against a panel of demethylases of the JMJ family.
DIPG cells were seeded into 96-well plates and treated with panobinostat and GSK-J4 individually or in combination at the indicated concentrations for 72 hr in at least triplicate. Cell viabilities were then assessed using the CelltiterGlo assay relative to 0.1% DMSO control. Data shown as mean ± SD. *indicates the two drugs demonstrate synergy at that condition (i.e. CI < 1).
JIB-04 is a pan-selective Jumonji histone demethylase inhibitor with IC50 of 230, 340, 855, 445, 435, 1100, and 290 nM for JARID1A, JMJD2E, JMJD3, JMJD2A, JMJD2B, JMJD2C, and JMJD2D in cell-free assays, respectively.
G, Western blot analyses to monitor the amount of H3K9me3 in the presence of rhein and MMS (upper panel) and under the treatment of JIB-04 (lower panel).
ML324 is a selective inhibitor of jumonji histone demethylase (JMJD2) with IC50 of 920 nM.
IOX1 is a potent and broad-spectrum inhibitor of 2OG oxygenases, including the JmjC demethylases.
GSK-J1 is a highly potent H3K27 histone demethylase inhibitor with IC50 of 28 nM and 53 nM in cell-free assays for JMJD3 (KDM6B) and UTX (KDM6A), respectively, >10-fold selectivity over other tested demethylases.
Daminozide, a plant growth regulator, selectively inhibits the KDM2/7 JmjC subfamily with IC50 of 1.5±0.7 μM for KDM2A. It is at least 100-fold selective as an inhibitor of the KDM2/7 subfamily over the other demethylase subfamily members tested, with IC50s of 2 μM or less against KDM2A, PHF8, and KIAA1718 and IC50s of 127 μM for KDM3A or greater (mM range) against other demethylases.
GSK2879552 2HCl is a potent, selective, orally bioavailable, irreversible LSD1 inhibitor with Kiapp of 1.7 μM. Phase 1.
Effects of LSD1 inhibitors in acute myeloid leukaemia cells. Cells were exposed to drugs for 48 h or for the indicated times. Cell death and Dwm dissipation were determined by flow cytometric analyses of propidium iodide uptake or DiOC6(3) staining, respectively. Caspase 3/7 activity was determined using the fluorogenic substrate Ac-DEVD-AMC; relative caspase 3/7 activities are the ratio of treated cells to untreated cells. Means±SEM of each two (caspase 3/7 activity) or three (flow cytometric analyses) separate measurements are shown.
CP2 is a cyclic peptide that inhibits the JmjC histone demethylases KDM4 with IC50 values of 42 nM and 29 nM for KDM4A and KDM4C, respectively.