STAT3 Inhibitor XX, APT _STAT3-9R

A cell-permeable STAT3 inhibiting peptide that corresponds to the high affinity STAT3-interacting aptide APT_STAT3 (K_D = 231 nM), originally identified by phage peptide library screening, with the addition of 9 arginines at the C-terminus via a GGGGS linker sequence. Reported to inhibit JAK2-catalyzed STAT3 phosphorylation in cell-free kinase assays and suppress cellular STAT3 phosphorylation as well as DNA-binding activity (by 54% post 6 h 30 µM treatment) in human lung carcinoma A549 cultures, resulting in downregulation of cell cycle progression regulator cyclin D1 and reduced expression of anti-apoptic survivin & Bcl-xL, while exhibiting little effect toward cellular phosphorylation levels of STAT1/5 and Akt. Shown to inhibit A549 proliferation (GI₅₀ = 10 to 20 µM in 12 h by MTT assay; complete inhibition by 30 µM in 2-wk colony formation assay) via apoptosis induction (PI⁺/Annexin V⁺ population = 15% vs. 2.8% with or without 6 h 30 µM drug treatment) in vitro and intratumoral injection is efficacious in suppressing the growth of established tumors derived from B16F1 murine melanoma allograft as well as from human U87MG glioblastoma and A549 (8 mg/kg, q.o.d.) xenografts in mice in vivo. Binding study indicates that the majority of APT_STAT3 affinity is mediated via STAT2 SH2 domain interaction and only moderate affinity is detected toward DNA-binding domain (DBD).

A cell-permeable, 26-mer peptide (APT_STAT3) that binds to STAT3 with high affinity (K_d = 231 nM) and blocks its DNA binding activity.

A cell-permeable, 26-mer peptide (APT_STAT3) with tryptophan zipper scaffold that forms a robust β-hairpin structure and binds to STAT3 with high affinity (K_d = 231 nM) and blocks its DNA binding activity. Its cell permeability is conferred by fusion of peptide to 9 arginine residues via a GGGGS linker. Selectively targets SH2 domain of STAT3 and disrupts STAT3-JAK2 interaction and STAT3 phosphorylation (Tyr705) and dimerization without affecting STAT1 and STAT5. Shown to effectively reduce mRNA levels of cyclin D1, Bcl-xL, and survivin in A549 cells and suppresses their viability and proliferation (~10-20 µM). Exerts antitumor properties in both xenograft (8 mg/kg, q.o.d., intratumorally) and allograft tumors in BABL/c nude mice and prolongs their survival. Note: Tryptophen zipper sequence in parentheses; STAT3-targeting sequence underlined.

Please note that the molecular weight for this compound is batch-specific due to variable water content.

Cell permeable: yes

Primary Target
STAT3

Toxicity: Standard Handling (A)

H-His-Gly-Phe-Gln-Trp-Pro-Gly-(Ser-Trp-Thr-Trp-Glu-Asn-Gly-Lys-Trp-Thr-Trp-Lys)-Gly-Ala-Tyr-Gln-Phe-Leu-Lys-Gly-Gly-Gly-Gly-Ser-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-Arg-OH

Supplied as a trifluoroacetate salt.

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Kim, D., et al. 2014. Cancer Res.74, 2144.

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