Biochem/physiol Actions

Reversible: yes

Primary TargetK-Ras

Cell permeable: yes

General description

A cell-permeable hydrocarbon-stapled, α-helical peptide that mimics the native son of sevenless 1 (SOS1) helical domain (amino acids 929-944) with additional Arg-Arg tag for better cell permeability. Binds to wild-type and mutant KRAS at the SOS1 binding pocket in a sequence-specific manner and disrupts SOS1/KRAS interaction (EC₅₀ = 79, 61, 103, 129, 140, and 124 nM for wild-type, G12D, G12V, G12C, G12S, and Q61H mutants, respectively) and blocks their nucleotide association. Reported to engage both GDP-KRAS and GTP-KRAS. Shown to impair the viability of cancer cells bearing G12D, G12C, G12V, G12S, G13D, and Q61H mutations (IC₅₀ = 5 - 15 µM). Also diminishes the viability of HeLa and Colo320-HSR cells expressing wild-type KRAS. Inhibits the activity of MEK1/2, ERK1/2, and Akt in Panc10.05 cells treated with epidermal growth factor. Also shown to completely suppress the phosphorylation of Akt and ERK1/2 in Drosophila melanogaster expressing V12 mutant form of RAS85D upon RU486 (Cat. No. 475838) treatment.

Legal Information

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

Other Notes

Leshchiner, E. S. et al. 2015. Proc. Natl. Acad. Sci. USA.112, 1761.

Packaging

5 mg in Glass bottle

Packaged under inert gas

Physical form

Supplied as a trifluoroacetate salt.

Reconstitution

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

Sequence

Ac-RRFFGIXLTNXLKTEEGN (X=(S)-2-(4′-pentenyl)Ala, stapled)

Warning

Toxicity: Standard Handling (A)