Home Epigenetics Histone Methyltransferase inhibitor EI1

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EI1 Histone Methyltransferase inhibitor

Cat.No.S7611

EI1 is a potent and selective EZH2 inhibitor with IC50 of 15 nM and 13 nM for EZH2 (WT) and EZH2 (Y641F), respectively.
EI1 Histone Methyltransferase inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 390.48

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Quality Control

Batch: S761101 DMSO]42 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Purity: 99.52%
99.52

Solubility

In vitro
Batch:

DMSO : 42 mg/mL (107.55 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

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In vivo
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Chemical Information, Storage & Stability

Molecular Weight 390.48 Formula

C23H26N4O2

 Storage (From the date of receipt)
CAS No. 1418308-27-6 Download SDF Storage of Stock Solutions

Synonyms KB-145943 Smiles CCC(CC)N1C=CC2=C(C=C(C=C21)C#N)C(=O)NCC3=C(C=C(NC3=O)C)C

Mechanism of Action

Targets/IC50/Ki
EZH2 (Y641F)
(Cell-free assay)
13 nM
Ezh2 (wild-type)
(Cell-free assay)
15 nM
In vitro
In DLBCL cells, EI1 inhibits cellular H3K27 methylation and activates Ezh2 target gene p16 expression. In mouse embryonic fibroblasts, this compound also inhibits H3K27me3 and cell proliferation. In addition, it selectively inhibits the growth of DLBCL cells carrying Ezh2 mutation, and causes cell cycle arrest and apoptosis.
Kinase Assay
Biochemical Assay
For IC50 determination, EI1 is serial diluted threefold in DMSO for a total of 12 concentrations, with the starting concentration at 1 μM. The reaction is incubated at room temperature for 120 min, and stopped by adding quench solution (2.5% TFA with 320 nM d4-SAH). SAH production is quantitated using an API 4000 triple quadrupole mass spectrometry with Turbulon Spray coupled with Prominence UFLC. The percentage of inhibition is normalized using positive (no inhibitor) and negative (no enzyme) controls, and IC50 calculated using PRISM. Enzymology studies of S-Adenosyl methionine (SAM) competition are performed with slight modification of reaction condition: 10 μM of this compound is used as the starting dose for serial dilution. SAM is titrated over a range between 1 μM and 50 μM (corresponding to 1 × Km and 50 × Km), and substrate peptide is present in the final reaction mixture at its saturated condition (10 μM). For histone methyltransferase (HMT) profiling in Table 1, all HMTs are purified recombinant proteins from either Escherichia coli or Baculovirus system. The catalytic domain of G9a, SuV39H2, Set7/9, CARM1, SETD8, NSD3, SETD2, and Dot1L, and the full-length SmyD2 protein were used in the biochemical assays. HMT biochemical reactions are carefully characterized with enzymology studies and the SAM and substrate Km determined. The SAM and substrate concentrations are kept at their respective Km for most of the HMTs, except the ones (SmyD2 and Set7/9) with low SAM-Km value, for which 0.5 μM SAM is used. All HMT reactions are performed using the same assay format where the production of SAH from the biochemical reaction is quantitated by LC-MS.
References

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