BRD0705 是一种具有旁系选择性的、口服具有活性的GSK3α抑制剂，其 IC50=66 nM，Kd=4.8 μM。 它与 GSK3β (其 IC50=515 nM) 相比，对GSK3α的选择性更高 (8 倍)。它可用于研究急性髓细胞性白血病。

BRD0705 is a potent, paralog selective and orally active GSK3α inhibitor (IC50: 66 nM; Kd: 4.8 μM). BRD0705 displays increased selectivity for GSK3α (8-fold) versus GSK3β (IC50: 515 nM).

BRD0705 displays excellent selectivity in a penal of 311 kinases, the CDK family of kinases (CDK2, 3 and 5) are next most potently inhibits at values of 6.87 μM, 9.74 μM and 9.20 μM (87-fold, 123-fold and 116-fold selectivity relative to GSK3α). BRD0705 (10-40 μM; 2-24 hours; U937 cells) treatment impairs GSK3α Tyr279 phosphorylation in a time-and concentration-dependent manner without affecting GSK3β Tyr216 phosphorylation. BRD0705 impairs AML colony formation in all six tested cell lines, MOLM13, TF-1, U937, MV4-11, HL-60, and NB4, in a concentration-dependent manner, as opposed to BRD3731 which impairs colony formation in TF-1 while increasing colony-forming ability in the MV4-11 cell line.

In AML mouse models, BRD0705 (30 mg/kg; oral gavage; twice daily; NSG mice) treatment impairs leukemia initiation and prolongs survival.

2056261-41-5

C20H23N3O

321.42

DMSO:300 mg/mL (933.36 mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years