Sigma-Aldrich Hmtase Inhibitor Ix mm-102

Assay

≥95% (HPLC)

Quality Level

100

Form

powder

Potency

1 nM K_i

Manufacturer/Tradename

Calbiochem^®

Storage Condition

OK to freeze
desiccated (hygroscopic)
protect from light

Color

light beige

Solubility

DMSO: 100 mg/mL

Storage Temp.

−20°C

General Description

A cell-permeable peptidomimetic that competes against MLL1 (Mixed Lineage Leukemia 1) minimum essential WIN (WDR5 INteracting) motif (-Ala³⁷⁶⁴-Arg-Ala³⁷⁶⁶-) for WDR5 (Trp-Asp Repeat Domain 5) binding (IC₅₀/K_i= 2.5 nM/<1 nM and 540 nM/120 nM, respectively), effectively preventing MLL1 from complex assembling with WDR5, RbBP5 (Retinoblastoma Binding Protein 5), and ASH2L (Absent Small or Homeotic-2-Like) for enhanced H3K4 methyltransferase activity (IC₅₀= 0.4 nM). Shown to reduceHoxA9andMeis-1mRNA expression (by 76% and 36%, respectively, after 96 H 50 µM mm-102 treatment) in myeloblasts derived fromMLL1-AF9-transduced murine bone marrow cells and preferentially inhibit the growth of MLL1-AF4-harboring MV4;11 and MLL1-ENL-harboring KOPN8 leukemia cultures (GI₅₀in 7 days = 25 µM) via apoptosis induction (by >75% in 4 days in MV4:11 cultures; 50 µM mm-102), while exhibiting much reduced potency against BCR-ABL-dependent K562 cells (GI₅₀in 7 days = 84 µM; >90 live cells after 4-day 50 µM mm-102 treatment).A cell-permeable peptidomimetic that prevents MLL1 (Mixed Lineage Leukemia 1) from complex assembling with WDR5 (Trp-Asp Repeat Domain 5), RbBP5 (Retinoblastoma Binding Protein 5), and ASH2L (Absent Small or Homeotic-2-Like) for enhanced H3K4 methyltransferase activity (IC₅₀= 0.4 nM). Shown to reduceHoxA9andMeis-1mRNA expression in myeloblasts derived fromMLL1-AF9-transduced murine bone marrow cells (50 µM for 96 H) and preferentially inhibit the growth of MLL1-AF4-harboring MV4;11 and MLL1-ENL-harboring KOPN8 leukemia cultures (GI₅₀in 7 days = 25 µM) via apoptosis induction, while exhibiting much reduced potency against BCR-ABL-dependent K562 cells (GI₅₀in 7 days = 84 µM).

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

Biochem/Physiol Actions

Cell permeable: yesPrimary Target
WDR5Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.Use only fresh DMSO for reconstitution.

Other Notes

Karatas, H., et Al. 2013.J. Am. Chem. Soc. 135,669.CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany