GNE-781 是一种有效的，具有口服活性的选择性 CBP 抑制剂，在 TR-FRET 实验中 IC₅₀ 为 0.94 nM。GNE-781 还抑制 BRET 和 BRD4 (1)，IC₅₀ 分别为 6.2 nM 和 5100 nM。GNE-781 在 MOLM-16 AML 异种移植模型中显示抗肿瘤活性。

GNE-781 is an orally active, highly potent and selective CBP inhibitor with an IC 50 of 0.94 nM in TR-FRET assay. GNE-781 also inhibits BRET and BRD4(1) with IC 50 s of 6.2 nM and 5100 nM, respectively. GNE-781 displays antitumor activity in an MOLM-16 AML xenograft model.

Solid

IC50: 0.94 nM (CBP), 6.2 nM (BRET), 5100 nM (BRD4(1))

GNE-781 is a highly advanced potent and selective bromodomain inhibitor of cyclic adenosine monophosphate response element binding protein, binding protein (CBP). GNE-781 reduces FOXP3 (forkhead box P3) transcript levels. Examination of a subset of bromodomains reveals that GNE-781 is exquisitely selective for CBP/P300 and is remarkably selective for CBP (5425-fold) and P300 (4250-fold). GNE-781 demonstrates an appropriate balance of cell potency, selectivity (5425-fold over BRD4(1)) . has not independently confirmed the accuracy of these methods. They are for reference only.

GNE-781 (3-30 mg/kg; p.o.; twice daily for 21 days) has tumor growth inhibition (%TGI) is 73%, 71%, and 89% at 3, 10, and 30 mg/kg, respectively in SCID beige mice with MOLM-16 AML xenografts.
GNE-781 decreases Foxp3 transcript levels in a dose dependent manner. GNE-781 (3-30 mg/kg) suppresses MYC at doses as low as 3 mg/kg at 2 and 8 h, with maximal suppression at 10 and 30 mg/kg at 2 h (87% and 88% inhibition, respectively).
has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

-20°C, stored under nitrogen In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

[1]. Romero FA, et al. GNE-781, A Highly Advanced Potent and Selective Bromodomain Inhibitor of Cyclic Adenosine Monophosphate Response Element Binding Protein, Binding Protein (CBP). J Med Chem. 2017 Nov 22;60(22):9162-9183.

In Vitro: DMSO : 100 mg/mL (190.26 mM; Need ultrasonic)配制储备液