Home Epigenetics Histone Methyltransferase inhibitor - MLL inhibitor MM-102

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MM-102 Histone Methyltransferase inhibitor

Cat.No.S7265

MM-102 (HMTase Inhibitor IX) is a high-affinity peptidomimetic inhibitor of the WDR5/MLL1 protein-protein interaction, which bind to WDR5 with Ki < 1 nM and IC50 =2.4nM.This product may precipitate when dissolved in saline solution or PBS solution. It is recommended to prepare the stock solution in DMSO solution.
MM-102 Histone Methyltransferase inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 669.8

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: S726501 DMSO]100 mg/mL]false]Ethanol]100 mg/mL]false]Water]50 mg/mL]false Purity: 99.0%
99.0

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Rosetta 2 (DE3) pLysS Function assay Inhibition of MLL1 binding to N-terminal His-tagged WRD5 23 deletion mutant (24 to 334 residues) (unknown origin) expressed in Escherichia coli Rosetta 2 (DE3) pLysS cells by fluorescence polarization assay, Ki = 0.001 μM. 29254892
Rosetta 2 (DE3) pLysS Function assay Inhibition of MLL1 binding to N-terminal His-tagged WRD5 23 deletion mutant (24 to 334 residues) (unknown origin) expressed in Escherichia coli Rosetta 2 (DE3) pLysS cells by fluorescence polarization assay, IC50 = 0.0024 μM. 29254892
Rosetta2-(DE3) pLysS Function assay 5 hrs Inhibition of C-terminal 5-FAM-WIN peptide binding to N-terminal His-tagged WDR5 (24 to 334 residues) (unknown origin) expressed in Rosetta2-(DE3) pLysS cells after 5 hrs by fluorescence polarization assay, IC50 = 0.0024 μM. 27720555
MV4-11 Antiproliferative assay 72 hrs Antiproliferative activity against human MV4-11 cells harboring MLL-AF4 assessed as inhibition of cell viability after 72 hrs by CCK8-based colorimetric assay, IC50 = 20.7 μM. 27720555
MV4-11 Antiproliferative assay 72 hrs Antiproliferative activity against human MV4-11 cells harboring MLL-AF4 fusion protein after 72 hrs by CCK8 assay, IC50 = 20.7 μM. 27598236
MV4-11 Antiproliferative assay 7 days Antiproliferative activity against human MV4-11 cells harboring MLL-AF4 after 7 days by CellTiter-Glo luminescent cell viability Assay, IC50 = 25 μM. 27720555
MV4-11 Antiproliferative assay Antiproliferative activity against human MV4-11 cells harboring MLL-AF4 fusion protein by CellTiter-Glo assay, IC50 = 25 μM. 27598236
K562 Antiproliferative assay 72 hrs Antiproliferative activity against human K562 cells harboring BCR-ABL assessed as inhibition of cell viability after 72 hrs by CCK8-based colorimetric assay, IC50 = 37.8 μM. 27720555
K562 Growth inhibition assay 7 days Growth inhibition of human K562 cells after 7 days by MTS assay, IC50 = 37.8 μM. 27598236
MV4-11 Function assay 10 uM 7 days Inhibition of MLL1-WDR5 protein-protein interaction in human MV4-11 cells harboring MLL-AF4 fusion protein assessed as inhibition of MLL1 histone methyltransferase activity by measuring reduction in H3K4me2 level at 10 uM after 7 days by Western blot meth 27598236
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight 669.8 Formula

C35H49F2N7O4

 Storage (From the date of receipt)
CAS No. 1417329-24-8 Download SDF Storage of Stock Solutions

Synonyms HMTase Inhibitor IX Smiles CCC(CC)(C(=O)NC(CCCN=C(N)N)C(=O)NC1(CCCC1)C(=O)NC(C2=CC=C(C=C2)F)C3=CC=C(C=C3)F)NC(=O)C(C)C

Solubility

In vitro
Batch:

DMSO : 100 mg/mL ( (149.29 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 100 mg/mL

Water : 50 mg/mL

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

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.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC50/Ki
WDR5 [1]
(Cell-free assay)
2.4 nM
In vitro
MM-102, as a MLL1 mimetic, shows high binding affinities to WDR5 with IC50 of 2.9 nM and Ki of < 1 nM. In the MLL1-AF9 transduced murine cells, this compound specifically reduces expression of two critical MLL1 target genes (HoxA9 and Meis-1), which are required for MLL1 mediated leukemogenesis. In addition, it effectively and selectively inhibits cell growth and induces apoptosis in leukemia cells harboring MLL1 fusion proteins. [1]
Kinase Assay
In Vitro Histone Methyltransferase (HMT) Assay
The HMT assay is performed in 50 mM HEPES pH 7.8, 100 mM NaCl, 1.0 mM EDTA, and 5% glycerol at 22 °C. Each reaction contains 1.5 μCi of the co-factor, 3H-S-adenosylmethionine. H3 10-residue peptide is used as the substrate at 50 μM. This compound is added at concentrations ranging from 0.125 to 128 μM and incubated with the pre-assembled WDR5/RbBP5/ASH2L complex at a final concentration of 0.5 μM for each protein for 2–5 min. Reactions are initiated by addition of the MLL1 protein at a final concentration of 0.5 μM and allowed to proceed for 30 min before preparing scintillation counting. To count samples, reactions are spotted on separate squares of P81 filter paper and precipitated by submerging in freshly prepared 50 mM sodium bicarbonate buffer with pH 9.0. After washing and drying, samples are vortexed in Ultima Gold scintillation fluid and counted. As a negative control, assays are performed using 0.5 μM MLL1/WDR5/RbBP5/ASH2L complex assembled with the non-interacting mutant, WDR5D107A.
References

Applications

Methods Biomarkers Images PMID
Growth inhibition assay Cell viability S7265-viability1 23210835

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