Notch Transcription Factor Inhibitor, SAHM1 - Calbiochem (C15-1304-023)

General description

A cell-permeable, stabilized hydrocarbon-stapled α-helical peptide that targets a critical protein-protein interface and prevents assembly in the NOTCH1 trans-activation complex. Soluble FITC-SAHM1 was found to bind the pre-formed RAMANK-CSL complex (K_d = 0.12 µM) competitively with MAML1, whereas the unmodified FITC-MAML1 (21-36) peptide bound the complex with markedly diminished affinity in an in vitro pull down assay. Treatment of KOPT-K1 cell lines with 20 µM of compound results in the suppression of NOTCH1 target genes, HES4, DTX1, and HES1. A consistent repressive effect on NOTCH1-activated gene expression by this compound was observed across a panel of human T-ALL cell lines, containing diverse mutant NOTCH1 alleles. In HeLa cells, this peptide also inhibited the expression of ICN1 (IC₅₀ = 6.56 µM) dose-dependently in a luciferase reporter-gene assay, as well as that of β-lactamase (IC₅₀<2.5 µM) in a second reporter-gene assay. Furthermore, treatment with this peptide inhibits NOTCH-mediated proliferation in cultured cells at 15 µM, and in a mouse model of T-ALL cells at 30 mg/kg twice daily.

Warning

Toxicity: Standard Handling (A)

Sequence

Acetyl-βAla-ERLRRRI*LCR*HHST

* = Two S5 molecules (a non-natural alkenyl amino acid) stapled together with a double bond

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Other Notes

Moellering, R.E., et al. 2009. Nature462, 182.

Legal Information

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

Molecular Weight: 3228.95. Empirical Formula: C₉₄H₁₆₂N₃₆O₂₃S · 7C₂HF₃O₂ · 13H₂O. Quality Level: 100. Assay: ≥. 93% (HPLC). form: solid. manufacturer/tradename: Calbiochem^®. . storage condition: OK to freeze. color: off-white. solubility: DMSO: 50 . mg/mL. shipped in: wet ice. storage temp.: −. 20°C. Storage Class Code: 11 - Combustible Solids. WGK: WGK 1. Flash Point(F): Not applicable. Flash Point(C): Not applicable.