BP-1-102 is an orally active, effective and specific STAT3 inhibitor. BP-1-102 binds Stat3 (Kd: 504 nM), then blocks Stat3-phosphotyrosine (pTyr) peptide interactions and Stat3 activation (4-6.8 μM), and selectively inhibits migration, survival, growth, and invasion of Stat3-dependent tumor cells. The BP-1-102-mediated inhibition of aberrantly active Stat3 in tumor cells suppresses the expression of c-Myc, Bcl-xL, Cyclin D1, Survivin, and VEGF.

STAT3:504 nM(Kd)

BP-1-102通过504 nM的亲和力(KD)结合Stat3，阻断Stat3-磷酸化酪氨酸(pTyr)肽段相互作用，抑制Stat3依赖型肿瘤细胞的生长、存活、迁移和侵袭。BP-1-102对异常活跃的Stat3在肿瘤细胞中的抑制作用导致c-Myc、Cyclin D1、Bcl-xL、Survivin和VEGF表达下调。用BP-1-102处理乳腺癌细胞进一步阻断了Stat3–NF-κB的交流，颗粒细胞集落刺激因子、可溶性细胞间黏附分子1、巨噬细胞迁移抑制因子/糖基化抑制因子、白细胞介素1受体拮抗剂及丝氨酸蛋白酶抑制蛋白1的释放，以及焦点粘附激酶和paxillin的磷酸化。BP-1-102在体外抑制Stat3 DNA结合活性，IC50值为6.8±0.8 μM，优先抑制Stat3-Stat3、相较于Stat1-Stat3、Stat1-Stat1或Stat5-Stat5的DNA结合活性。BP-1-102对phospho-Shc、Src、Jak-1/2、Erk1/2或Akt水平几乎没有影响[1]。

静脉注射或口服灌胃给药BP-1-102可在肿瘤组织中达到微摩尔或微克水平，抑制人乳腺和肺肿瘤异种移植物的生长，并调节Stat3活性、Stat3靶基因和体内可溶性因子。BP-1-102选择性地抑制含有持续激活的stat3的恶性细胞的生长、存活、恶性转化、迁移和侵袭。在血浆中，BP-1-102的浓度可达到微摩尔水平，在肿瘤组织中以微克形式检测到[1]。

Kinase targets are tested with biochemical enzymatic kinase assays using the SelectScreen Kinase Profiling Service to determine IC50 values. The compounds (XMD8-87) are assayed at 10 concentrations (3-fold serial dilutions starting from 1 μM) at an ATP concentration equal to the ATP Km[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 BP-1-102 for up to 96 h. Viable cells are counted by trypan blue exclusion/phase-contrast microscopy or assessed by a CyQUANT Cell Proliferation Kit.(Only for Reference)