| References: |
SH5-07 is a hydroxamic acid based Stat3 inhibitor with an IC50 of 3.9±0.6 μM in in vitro assay.
In Vitro: SH5-07 is a hydroxamic acid analog of BP-1-102. SH5-07 dose-dependently inhibits Stat3 activity with an IC50 of 3.9±0.6 μM in in vitro assay. It preferentially inhibits Stat3:Stat3 DNA-binding activity, ahead of inhibiting Stat1:Stat3 activity, with minimal effects on Stat1:Stat1 activity. SH5-07 binds Stat3, disrupts Stat3 association with growth factor receptor, and thereby inhibits Stat3 phosphorylation. It induces antitumor cell effects against malignant cells harboring constitutively-active Stat3. SH5-07 inhibits the expression of known Stat3-regulated genes. Bcl-2, Bcl-xL, c-Myc, Survivin, Cyclin D1 and Mcl-1 expression is reduced in response to 24 h, 5 μM SH5-07 treatment.
In Vivo: Tail vein injection or oral gavage delivery of SH5-07 or SH4-54 inhibits growth of 90-150 mm3 established subcutaneous mouse xenografts of human glioma (U251MG) and breast (MDA-MB-231) tumors that harbor aberrantly-active Stat3, associated with decreased c-Myc, Mcl-1 and Cyclin D1 expression. No significant changes in body weights, blood cell counts, or the gross anatomy of organs, or obvious signs of toxicity are observed. |
