BP-1-102

BP-1-102 binds Stat3 with an affinity (KD) of 504 nM, blocks Stat3-phospho-tyrosine (pTyr) peptide interactions and Stat3 activation at 4-6.8 μM, and selectively inhibits growth, survival, migration, and invasion of Stat3-dependent tumor cells. This compound-mediated inhibition of aberrantly active Stat3 in tumor cells suppresses the expression of c-Myc, Cyclin D1, Bcl-xL, Survivin, VEGF, and Krüppel-like factor 8, which is identified as a Stat3 target gene that promotes Stat3-mediated breast tumor cell migration and invasion. Treatment of breast cancer cells with this chemical further blocks Stat3–NF-κB cross-talk, the release of granulocyte colony-stimulating factor, soluble intercellular adhesion molecule 1, macrophage migration-inhibitory factor/glycosylation-inhibiting factor, interleukin 1 receptor antagonist, and serine protease inhibitor protein 1, and the phosphorylation of focal adhesion kinase and paxillin, while enhancing E-cadherin expression. It inhibits Stat3 DNA-binding activity in vitro, with an IC50 value of 6.8±0.8 μM and preferentially inhibits Stat3-Stat3, over Stat1-Stat3, Stat1-Stat1, or Stat5-Stat5 DNA-binding activity. This agent has little or no effect on phospho-Shc, Src, Jak-1/2, Erk1/2, or Akt levels^[1].

Intravenous or oral gavage delivery of BP-1-102 furnishes micromolar or microgram levels in tumor tissues and inhibits growth of human breast and lung tumor xenografts and modulates Stat3 activity, Stat3 target genes, and soluble factors in vivo. This compound selectively suppresses growth, survival, malignant transformation, migration, and invasion of malignant cells harboring constitutively active stat3. It is detectable at micromolar concentrations in plasma and in micrograms in tumor tissues^[1].

Proliferating cells in 6- or 96-well plates are treated once with 0–30 μM BP-1-102 for 24 h or with 10 μM this compound for up to 96 h. Viable cells are counted by trypan blue exclusion/phase-contrast microscopy or assessed by a CyQUANT Cell Proliferation Kit.

• https://pubmed.ncbi.nlm.nih.gov/22623533/