A1331852是一种具有口服活性的BCL-XL选择性抑制剂，Ki值小于10 pM。它可用于治疗癌症、免疫和自身免疫疾病。

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

A-1331852 exhibits remarkable potency both as a single agent and in combination with TKIs in killing primary CD34+ CML cell. Also, It has remarkable potency in inducing apoptosis in these cells at low nanomolar concentrations as early as 1 h post-treatment[2].

A-1331852 demonstrates antitumor efficacy in the Molt-4 xenograft model, inducing tumor regressions as a single agent[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.

1430844-80-6

C38H38N6O3S

658.82

Ethanol:<1 mgml
H2O:<1 mgml
DMSO:93 mg/mL (141.2 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years