SML4473

EL133, Keap1 PINCH

≥96% (HPLC)

• Synonym(e): N28,N28′-[1,2-ethanediylbis(oxy-2,1-ethanediyl)]bis[2-cyano-3,12-dioxo-Oleana-1,9(11)-dien-28- amide
• Empirische Formel (Hill-System): C₆₈H₉₄N₄O₈
• CAS-Nummer: 3066985-46-1
• Molekulargewicht: 1095.50
• UNSPSC Code: 12352200
• Assay: ≥96% (HPLC)
• Form: powder

Eigenschaften

• Quality Segment: 100
• assay: ≥96% (HPLC)
• form: powder
• color: white to beige
• solubility: DMSO: 2 mg/mL, clear
• storage temp.: -10 to -25°C

Beschreibung

Biochem/physiol Actions

EL133 is a highly cell-permeable Polymerization-Inducing Chimera (PINCH) rationally designed to exploit protein symmetry (homodimerism) as a selective vulnerability for functional protein knockout. Comprising two bardoxolone (BDX) moieties conjugated via a precise short polyethylene glycol (PEG2) linker, EL-133 acts as a covalent molecular bridge targeting Cysteine 151 (C151) within the Keap1 BTB domain to induce supramolecular assembly. This mechanism drives the rapid (>90%) and high-specificity precipitation of Keap1 from the soluble cytosolic fraction (insolubility EC50 = 102 nM in OCI-AML2; effective >500 nM), with global proteomics confirming COL1A1 as the sole significant off-target. By locking Keap1 in an inactive polymeric state, EL133 triggers robust, proteasome-independent activation of the Nrf2 pathway and Antioxidant Response Element (ARE) genes, resulting in distinct, sustained upregulation of NAD(P)H quinone dehydrogenase 1 (NQO1). Distinct from PROTACs or simple inhibitors, EL-133 functions as an autonomous sequestrator independent of cellular degradation machinery (lysosome/proteasome) or E3 ligase co-expression, effectively circumventing resistance mechanisms associated with effector dependency.

Sicherheitshinweise

• Piktogramme: GHS07
• Signalwort: Warning
• Gefahrencodes: H315,H317,H319
• Sicherheitshinweise: P261 - P264 - P272 - P280 - P302 + P352 - P305 + P351 + P338
• Hazard Classifications: Eye Irrit. 2 - Skin Irrit. 2 - Skin Sens. 1B
• Lagerklasse: 11 - Combustible Solids
• Flammpunkt (°F): Not applicable
• Flammpunkt (°C): Not applicable