5.30750

STAT3 Inhibitor XX, APT _STAT3-9R

• Synonym(s): STAT3 Inhibitor XX, APT _STAT3-9R, H₂N- HGFQWPG(SWTWENGKWTWK)G AYQFLK-GGGGS-RRRRRRRRR-CO₂H
• Empirical Formula (Hill Notation): C₂₂₃H₃₃₀N₈₀O₅₁
• Molecular Weight: 4947.51
• UNSPSC Code: 12352200
• NACRES: NA.77

Properties

• Assay: ≥95% (HPLC)
• Quality Level: 100
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; desiccated (hygroscopic); protect from light
• color: white
• solubility: H₂O: 50 mg/mL
• storage temp.: 2-8°C

Description

General description

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.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
STAT3

Warning

Toxicity: Standard Handling (A)

Sequence

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

Physical form

Supplied as a trifluoroacetate salt.

Reconstitution

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

Other Notes

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

Legal Information

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

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 1
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable