5.00649

HMTase Inhibitor IX, MM-102

• Synonym(e): HMTase Inhibitor IX, MM-102, Histone Methyltransferase Inhibitor IX, MM102, ( S)-N-( bis(4-Fluorophenyl)methyl)-1-(2-(2-ethyl-2-isobutyramidobutanamido)-5-guanidinopentanamido)cyclopentanecarboxamide, TFA, Histone Methyltransferase Inhibitor IX, MM102, (S)-N-(bis(4-Fluorophenyl)methyl)-1-(2-(2-ethyl-2-isobutyramidobutanamido)-5-guanidinopentanamido)cyclopentanecarboxamide, TFA
• Empirische Formel (Hill-System): C₃₅H₄₉F₂N₇O₄ · xC₂HF₃O₂
• Molekulargewicht: 669.80 (free base basis)
• UNSPSC-Code: 12352200
• NACRES: NA.77

Eigenschaften

• Assay: ≥95% (HPLC)
• Qualitätsniveau: 100
• Form: powder
• Wirksamkeit: 1 nM K_i
• Hersteller/Markenname: Calbiochem^®
• Lagerbedingungen: OK to freeze; desiccated (hygroscopic); protect from light
• Farbe: light beige
• Löslichkeit: DMSO: 100 mg/mL
• Lagertemp.: −20°C

Beschreibung

Allgemeine Beschreibung

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 reduce HoxA9 and Meis-1 mRNA expression (by 76% and 36%, respectively, after 96 h 50 µM MM-102 treatment) in myeloblasts derived from MLL1-AF9-transduced murine bone marrow cells and preferentially inhibit the growth of MLL1-AF4-harboring MV4;11 and MLL1-ENL-harboring KOPN8 leukemia cultures (GI₅₀ in 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 (GI₅₀ in 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 reduce HoxA9 and Meis-1 mRNA expression in myeloblasts derived from MLL1-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 (GI₅₀ in 7 days = 25 µM) via apoptosis induction, while exhibiting much reduced potency against BCR-ABL-dependent K562 cells (GI₅₀ in 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. Wirkung

Cell permeable: yes

Primary Target
WDR5

Reversible: yes

Verpackung

Packaged under inert gas

Warnhinweis

Toxicity: Standard Handling (A)

Rekonstituierung

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.

Sonstige Hinweise

Karatas, H., et al. 2013. J. Am. Chem. Soc.135, 669.

Rechtliche Hinweise

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Sicherheitshinweise

• Lagerklassenschlüssel: 11 - Combustible Solids
• WGK: WGK 2
• Flammpunkt (°F): Not applicable
• Flammpunkt (°C): Not applicable