MM-102

Catalog No.S7265 Batch:S726501

Technical Data

Formula

C₃₅H₄₉F₂N₇O₄

Molecular Weight

669.8

CAS No.

1417329-24-8

Solubility (25°C)*

In vitro

DMSO

100 mg/mL (149.29 mM)

Ethanol

100 mg/mL (149.29 mM)

Water

50 mg/mL (74.64 mM)

In vivo (Add solvents to the product individually and in order)

	5% DMSO 1 95% Corn oil	0.83mg/ml
	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	5.0mg/ml

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

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.

Targets

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 K_i of < 1 nM. In the MLL1-AF9 transduced murine cells, MM-102 specifically reduces expression of two critical MLL1 target genes (HoxA9 and Meis-1), which are required for MLL1 mediated leukemogenesis. In addition, MM-102 effectively and selectively inhibits cell growth and induces apoptosis in leukemia cells harboring MLL1 fusion proteins. ^[1]

Protocol (from reference)

Kinase Assay:^{^[1]}	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. Compounds are 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.
Cell Assay:^{^[1]}	Cell lines MV4;11, KOPN8, and K562 cells Concentrations ~100 μM Incubation Time 7 days Method MV4;11, KOPN8, and K562 cells are cultured in RPMI 1640 medium (ATCC) supplemented with 10% fetal bovine serum and 100 U/L penicillin-streptomycin and incubated at 37 °C under 5% CO₂. Cells are seeded into 12-well plates for suspension at a density of 5 × 10⁵ per well (1 mL) and treated with either vehicle control (DMSO, 0.2%) or MM-102 for 7 days. The medium is changed every 2 days, and compounds are resupplied. The CellTiter-Glo Luminescent Cell Viability Assay kit is used following the manufacturer’s instruction. First, 100 μL of the assay reagent is added into each well, and the content is mixed for 2 min on an orbital shaker to induce cell lysis. After 10 min incubation at room temperature, the luminescence is read on a microplate reader.

Kinase Assay:^{^[1]}

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. Compounds are 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.

Cell Assay:^{^[1]}

Cell lines
MV4;11, KOPN8, and K562 cells
Concentrations
~100 μM
Incubation Time
7 days
Method
MV4;11, KOPN8, and K562 cells are cultured in RPMI 1640 medium (ATCC) supplemented with 10% fetal bovine serum and 100 U/L penicillin-streptomycin and incubated at 37 °C under 5% CO₂. Cells are seeded into 12-well plates for suspension at a density of 5 × 10⁵ per well (1 mL) and treated with either vehicle control (DMSO, 0.2%) or MM-102 for 7 days. The medium is changed every 2 days, and compounds are resupplied. The CellTiter-Glo Luminescent Cell Viability Assay kit is used following the manufacturer’s instruction. First, 100 μL of the assay reagent is added into each well, and the content is mixed for 2 min on an orbital shaker to induce cell lysis. After 10 min incubation at room temperature, the luminescence is read on a microplate reader.

References

[1] Karatas H, et al. J Am Chem Soc. 2013, 135(2), 669-682.

Customer Product Validation

: Data from [Data independently produced by , , Cell Physiol Biochem, 2018, 45(4):1529-1540]

: Data from [Data independently produced by , , Mol Cell Biol, 2015, 36(4):615-27]

: Data from [Data independently produced by , , Int J Biol Sci, 2018, 14(9):1122-1132]

: Data from [Data independently produced by , , Biochem Biophys Res Commun, 2016, 469(1):108-13]

Selleck's MM-102 has been cited by 21 publications

Fibroblast-specific PRMT5 deficiency suppresses cardiac fibrosis and left ventricular dysfunction in male mice [ Nat Commun, 2024, 15(1):2472]	PubMed: 38503742
Arachidonic acid released by PIK3CA mutant tumor cells triggers malignant transformation of colonic epithelium by inducing chromatin remodeling [ Cell Rep Med, 2024, S2666-3791(24)00179-4]	PubMed: 38614093
MBD2 regulates the progression and chemoresistance of cholangiocarcinoma through interaction with WDR5 [ J Exp Clin Cancer Res, 2024, 43(1):272]	PubMed: 39350229
Deficiency of lncRNA MERRICAL abrogates macrophage chemotaxis and diabetes-associated atherosclerosis [ Cell Rep, 2024, 43(3):113815]	PubMed: 38428421
H4K20me1 plays a dual role in transcriptional regulation of regeneration and axis patterning in Hydra [ Life Sci Alliance, 2023, 6(5)e202201619]	PubMed: 36944423
Glioblastoma stem cell-specific histamine secretion drives pro-angiogenic tumor microenvironment remodeling [ Cell Stem Cell, 2022, S1934-5909(22)00417-9]	PubMed: 36265493
H3-K27M-mutant nucleosomes interact with MLL1 to shape the glioma epigenetic landscape [ Cell Rep, 2022, 39(7):110836]	PubMed: 35584667
Innate Immune Training of Human Macrophages by Cathelicidin Analogs [ Front Immunol, 2022, 13:777530]	PubMed: 35958593
Targeting matrix metallopeptidase 2 by hydroxyurea selectively kills acute myeloid mixed-lineage leukemia [ Cell Death Discov, 2022, 8(1):180]	PubMed: 35396375
Inhibition of Wdr5 Attenuates Ang-II-Induced Fibroblast-to-Myofibroblast Transition in Cardiac Fibrosis by Regulating Mdm2/P53/P21 Pathway [ Biomolecules, 2022, 12(11)1574]	PubMed: 36358925

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SHIPPING AND STORAGE
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