BRD0705

Research use only, not for human use.

BRD0705 (BRD-0705) is a potent, paralog-selective GSK3α inhibitor with IC50 of 66 nM.

BRD0705 (BRD-0705) is a potent, paralog-selective GSK3α inhibitor with IC50 of 66 nM, 8-fold selectivity over GSK3β (IC50=515 nM); displays excellent selectivity in a penal of 311 kinases, the CDK family of CDK2, CDK3 and CDK5) are most potently inhibited with IC50 of 6.87, 9.74 and 9.20 uM (87-, 123-, and 116-fold selectivity relative to GSK3α); inhibits GSK3α kinase function, impairs GSK3α Tyr279 phosphorylation in a time- and concentration-dependent manner without affecting GSK3β Tyr216 phosphorylation, and does not stabilize β-catenin, induces myeloid differentiation and impairs colony formation in AML cells, with no apparent effect on normal hematopoietic cells; impairs leukemia initiation and prolongs survival in AML mouse models.

Western Blot Analysis Cell Line:U937 cells Concentration:10 μM, 20 μM and 40 μM Incubation Time:2 hours, 4 hours, 8 hours and 24 hours Result:Impaired GSK3α Tyr279 phosphorylation in a time-and concentration-dependent manner without affecting GSK3β Tyr216 phosphorylation.

Animal Model:8-week-old male NSG mice injected with MLL-AF9 AML cells Dosage:30 mg/kg Administration:Oral gavage; twice daily Result:Mice survival was significantly improved.

BRD-0705 | BRD 0705

PI3K/Akt/mTOR signaling

GSK-3

GSK-3

——

——

2056261-41-5

321.424

C20H23N3O

>98% (HPLC)

In Vitro:?DMSO : 300 mg/mL (933.36 mM)

——

(S)-4-ethyl-7,7-dimethyl-4-phenyl-2,4,6,7,8,9-hexahydro-5H-pyrazolo[3,4-b]quinolin-5-one

(-20℃)

With Ice Pack

≥ 2 years