BIX-01294 Trihydrochloride is a G9a-like protein and G9a histone lysine methyltransferase inhibitor with IC50 values of 0.7 and 1.7 μM respectively. BIX-01294 inhibits the G9aHMTase dependent levels of histone-3 lysine (9) methylation (H3K9me). BIX-01294 can also inhibit H3K9 Jumonji demethylase KIAA1718 with half-maximal inhibitory concentrations in low micromolar range. In its inhibition of the histone lysine methyltransferases, BIX 01294 does not compete with cofactor S-adenosyl-methionine. The target enzyme is G9a, and it selectively impairs G9a HMTase and the generation of H3K9me2 in vitro. BIX-01294 (4.1 μM) reduces H3K9me2 Levels in bulk histone preparations from wt ES cells, mouse embryonic fibroblasts and HeLa cells. BIX-01294 reduces H3K9me2 at Several G9a Target Genes including Bim1 and Serac1.
|Source||Cancer Cell Int (2015). Figure 1. BIX 01294|
|Method||Western blot analysis|
|Cell Lines||human bladder cancer cells|
|Concentrations||1.25, 2.5, 5, 10 and 20 μmol/l|
|Incubation Time||24 h|
|Results||In summary, BIX-01294, as a specific inhibitor of EHMT2, induces caspase-dependent apoptosis in a dose- and time-dependent manner in human bladder cancer cells.|
|Cell lines||MCF-7 cells|
|Preparation method||MCF-7 cells treated with 10 μM BIX were fixed in 4% glutaraldehyde. After dehydration, ultrathin sections were prepared using a Sorvall MT5000 microtome (DuPont Instruments, MT5000), and collected on 150 mesh copper grids. Sections were stained with 1% uranyl acetate and/or lead citrate, and images obtained with a JEOL 100CX transmission electron microscope (JEOL USA, JEOL-100CX).|
|Incubation time||24 h|
|Animal models||C57BL/6 mice|
|Administration||injected through implanted cannula|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 90 mg/mL
Water 90 mg/mL
An analog of BIX-01294 selectively inhibits a family of histone H3 lysine 9 Jumonji demethylases.
Upadhyay AK, et al. J Mol Biol. 2012 Feb 24;416(3):319-27. PMID: 22227394.
Structural basis for G9a-like protein lysine methyltransferase inhibition by BIX-01294.
Chang Y, et al. Nat Struct Mol Biol. 2009 Mar;16(3):312-7. PMID: 19219047.
Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase.
Kubicek S, et al. Mol Cell. 2007 Feb 9;25(3):473-81. PMID: 17289593.
|Related Histone Methyltransferase Products|
BIX-01294 is a potent chemical inhibitor of G9a methyltransferase that catalyzes the mono-and di-methylation of the lysine 9 residue of histone H3, with IC50 of 1.9 μM.
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SGC0946 is a highly potent and selective DOT1L methyltransferase inhibitor with IC50 of 0.3 nM; selectively kill mixed lineage leukaemia cells.
UNC0642 is a potent, selective inhibitor of histone methyltransferases G9a/GLP with IC50s less than 2.5 nM for G9a and GLP and shows more than 300-fold selective for G9a and GLP over a broad range of kinases, GPCRs, transporters, and ion channels.
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