|
Notch Transcription Factor Inhibitor, SAHM1
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 (Kd = 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.
产品信息
Peptide Sequence Acetyl-βAla-ERLRRRI*LCR*HHST
* = Two S5 molecules (a non-natural alkenyl amino acid) stapled together with a double bond
Form Off-white solid
Molar mass 3228.9
Purity ≥93% by HPLC
Solubility DMSO
Chemical formula C94H162N36O23S• 7CF3CO2H•13H2O
商店和运输信息
Storage -20°C
Ship Shipped with Blue Ice or with Dry Ice
Standard Handling |