SH5-07 is a hydroxamic acid-based Stat3 inhibitor (IC50: 3.9 μM).

STAT3:3.9 μM (cell free)

SH5-07是BP-1-102的羟胺酸类似物。SH5-07剂量依赖性抑制Stat3活性（IC50: 3.9±0.6 μM，体外实验）。它优先抑制Stat3:Stat3 DNA结合活性，而不是Stat1:Stat3活性，并对Stat1:Stat1活性影响最小。SH5-07与Stat3结合，破坏Stat3与生长因子受体的关联，从而抑制Stat3磷酸化。SH5-07对携带持续活跃Stat3的恶性细胞产生抗肿瘤细胞效应。SH5-07能够抑制已知的Stat3调控基因的表达。经过24小时，5 μM SH5-07处理后，Bcl-xL、Bcl-2、c-Myc、Survivin、Cyclin D1和Mcl-1的表达减少。

通过尾静脉注射或口服灌胃方式给予SH5-07能够抑制已建立的皮下小鼠异种移植的人类胶质瘤（U251MG）和乳腺（MDA-MB-231）肿瘤的生长，其大小范围为90-150 mm^3，这些肿瘤中存在异常活跃的Stat3，与之相关的是Mcl-1、c-Myc和Cyclin D1表达的降低。未观察到体重、血细胞计数或器官的总体解剖结构有显著变化，也没有明显的毒性迹象。

Cells are treated with 0-8 μM agent for 24-48 h. For cell cycle profile analysis, cells are harvested and fixed with 70% ice-cold ethanol and stained with propidium iodide (PI). For apoptosis analysis, cells are collected and stained with FITC-Annexin V using the Apoptosis Detection Kit. Both the DNA content of cells and the Annexin V-positive cells are analyzed by the flow cytometer. Cell cycle phase distribution is analyzed using the Cell-Fit program. Data acquisition is gated to exclude cell doublets.

Mice are injected subcutaneously in the left flank area with U251MG cells in 200 μL of PBS/Matrigel matrix, or MDA-MB-231 cells in 100 μL of PBS. Mice with tumors of 90-150 mm^3 (MDA-MB-231) or 150 mm^3 (U251MG) are grouped for identical mean tumor sizes, administered 3, 5 or 6 mg/kg SH5-07 via oral gavage daily or tail vein injection every 2 or 3 days, and monitored every 3-7 days. Tumor sizes are measured with calipers and converted to tumor volume.