A-1331852 is a potent and selectiveBCL-XL inhibitor and may be useful in the treatment of cancer, immune and autoimmune diseases.

BCL-W:4 nM (Ki), BCL-XL:0.01 nM (Ki), BCL2:6 nM (Ki), MCL1:142 nM (Ki)

A-1331852 在作为单一化合物以及与TKIs联合应用时，对原发性CD34+ CML细胞具有显著的杀伤效力。此外，它能在低纳摩尔浓度下，治疗后最早于1小时内诱导这些细胞发生凋亡，表现出显著的效力[2]。

A-1331852在Molt-4异种移植模型中显示了抗肿瘤效果，作为单一化合物诱导肿瘤退缩[1]。

Rabbit or mouse E1 (apper 250 ng) is incubated with 32P-ubiquitin in 1× reaction buffer [50 mM Tris (pH 7.4), 0.2 mM ATP, 0.5 mM MgCl2] at room temperature for 15 min. In some experiments, the His-tagged mouse E1 is bound to TALON cobalt affinity resin before carrying out incubations and reactions. Mouse E1 and 32P-ubiquitin are added to the beads in 1× reaction buffer and incubated as for E1 reactions. Samples are heated in nonreducing SDS-PAGE sample buffer and resolved by SDS-PAGE. Thioesters with ubiquitin are visualized by Storm PhosphoImager.

Immunoprecipitation of BCL-XL is carried out in K562 cells, exposed to A-1331852 (100 nM) for 0-2 h, and the eluted complexes are immunoblotted for the indicated proteins. The input cell lysates and the immunodepleted supernatant (labeled as Flow-through) are immunoblotted to check the efficiency of the immunoprecipitation. (Only for Reference)

Mice: The growth inhibition of established tumors in SCID-bg mice is studied. A-1331852 is administered orally daily for 14 days at 25 mg/kg and docetaxel is administered intravenously at 7.5 mg/kg. The change of tumor volume is monitored daily. They are for reference only.