Home Epigenetics Epigenetic Reader Domain antagonist UNC1215

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UNC1215 Epigenetic Reader Domain antagonist

Cat.No.S7088

UNC1215 is a potent and selective MBT (malignant brain tumor) antagonist, which binds L3MBTL3 with IC50 of 40 nM and Kd of 120 nM, 50-fold selective versus other members of the human MBT family.
UNC1215 Epigenetic Reader Domain antagonist Chemical Structure

Chemical Structure

Molecular Weight: 529.72

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Chemical Information, Storage & Stability

Molecular Weight 529.72 Formula

C32H43N5O2

 Storage (From the date of receipt)
CAS No. 1415800-43-9 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles C1CCN(C1)C2CCN(CC2)C(=O)C3=CC(=C(C=C3)C(=O)N4CCC(CC4)N5CCCC5)NC6=CC=CC=C6

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (188.77 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Mechanism of Action

Features
The first chemical probe for a Kme-binding protein.
Targets/IC50/Ki
L3MBTL3 [1]
40 nM
L3MBTL3 [1]
120 nM(Kd)
L3MBTL3- D274A [1]
3.5 μM
In vitro
UNC1215 binds L3MBTL3, competitively displacing mono- or dimethyllysine-containing peptides. This probe is greater than 50-fold selective versus other members of the human MBT family. This compound has about a 75-fold selectivity for L3MBTL3 over L3MBTL1. It shows no activity at concentrations up to 30 μM against the tandem Tudor domain of UHRF1, the chromodomain of CBX7 or the PHD domain of JARID1A. X-ray crystallography identifies a unique 2:2 polyvalent mode of interaction between this chemical and L3MBTL3. In cells, it is nontoxic and directly binds L3MBTL3 via the Kme-binding pocket of the MBT domains. This compound increases the cellular mobility of GFP-L3MBTL3 fusion proteins, and point mutants that disrupt the Kme-binding function of GFP-L3MBTL3 phenocopy the effects of this chemical on localization. It is used to reveal a new Kme-dependent interaction of L3MBTL3 with BCLAF1, a protein implicated in DNA damage repair and apoptosis. [1]
Kinase Assay
AlphaScreen assay
Compound plates (1 μL at 10 or 30 mM highest concentration) are diluted in 1×assay buffer (20 mM Tris pH 8.0, 25 mM NaCl, 2 mM DTT and 0.05% Tween-20) over 2 steps using a Multimek robotic pipettor and 1 μL is spotted into the wells of 384-well assay Proxiplates. To these plates 9 μL of protein- peptide mix in 1× assay buffer is added by Multidrop and incubated for 30 min at room temperature. At this point 2 μL of streptavidin-conjugate donor and nickel-chelate acceptor beads (45 μg/mL in 1× assay buffer) are added, the plates are allowed to incubate for an additional 30 min in the dark at room temperature. After incubation the plates are read on EnVision mulilabel reader equipped with HTS alpha screen laser. The screens reported are performed up to 10 or 30 μM, and therefore it should be noted that those compounds referred to as inactive are indeed inactive only within the concentration range tested. PHF23 and JARID1A are GST tagged and consequently for these assays GST-acceptor beads are used. It should be noted that any positive binding curves for L3MBTL4 that are generated yielded curves with very shallow slopes, suggesting a nonspecific interaction. The data for the IC50 values is calculated from replicate runs in that the datapoints for each compound concentration are averaged and plotted using 4-parameters curve fitting.
References

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