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GNE-781
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
GNE-781图片
CAS NO:1936422-33-1
包装与价格:
包装价格(元)
1 mg电议
5 mg电议
10 mg电议
25 mg电议
50 mg电议
100 mg电议
200 mg电议
1 mL*10 mM(in DMSO)电议

产品介绍
GNE-781 是一种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。它还抑制BRET和BRD4 (1),IC50分别为 6.2 和 5100 nM,有抗肿瘤活性。

产品描述

GNE-781 is a highly potent and selective inhibitor of CBP (IC50: 0.94 nM in TR-FRET assay). GNE-781 also inhibits BRET and BRD4(1) (IC50s: 6.2 nM and 5100 nM, respectively).

体外活性

GNE-781 decreases FOXP3 (forkhead box P3) transcript levels. GNE-781 is a highly advanced potent and selective bromodomain inhibitor of cyclic adenosine monophosphate response element-binding protein, binding protein. GNE-781 is exquisitely selective for CBP/P300 and is remarkably selective for CBP (5425-fold) and P300 (4250-fold), which is shown by an examination of a subset of bromodomains. GNE-781 displays an appropriate balance of cell potency, selectivity (5425-fold over BRD4(1)) [1].

体内活性

GNE-781 is a highly potent and selective inhibitor of CBP that is efficacious in a MOLM-16 AML xenograft model. GNE-781 shows antitumor activity in an AML tumor model and is also shown to reduce Foxp3 transcript levels in a dose-dependent manner and it also shows moderate to low clearance in vivo in all species evaluated, with acceptable oral bioavailability. The effect of GNE-781 is determined in an in vivo PK/PD experiment using a MOLM-16 (adult AML cell line) xenograft mouse model. GNE-781(3 and 30 mg/kg; Single doses) are given in MOLM-16 tumor-bearing animals, and samples are collected at time points covering 2-24 h. Upon tumor establishment, Administration with GNE-781(3-30 mg/kg; twice daily ). Single-agent efficacy is observed at all doses, as evidenced by inhibition of MOLM-16 tumor growth. Tumor growth inhibition (%TGI) is 73%, 71%, and 89% at 3, 10, and 30 mg/kg, respectively. All doses of GNE-781 are well tolerated over the 21-day dosing window, with a maximal body weight loss of 3.7%. Tumor RNA is generated and used to assess MYC transcript by quantitative RT-PCR relative to vehicle-treated animals. At doses as low as 3 mg/kg at 2 and 8 h, suppression of MYC is observed, with maximal suppression observed at 10 and 30 mg/kg at 2 h (87% and 88% inhibition, respectively). To evaluate the in vivo efficacy of GNE-781, MOLM-16 AML xenografts are established in SCID beige mice[1].

Cas No.

1936422-33-1

分子式

C27H33F2N7O2

分子量

525.59

别名

GNE-781

储存和溶解度

DMSO:95 mg/mL (180.75 mM),Need ultrasonic
Ethanol:95 mg/mL (180.75 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years