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GNE-049
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-049图片
CAS NO:1936421-41-8
规格:98%
分子量:510.58
包装与价格:
包装价格(元)
5mg电议
10mg电议
50mg电议
100mg电议

产品介绍
GNE-049是一种高效的选择性CBP抑制剂,在TR-FRET实验中IC50为1.1nM。GNE-049还抑制BRET和BRD4(1),IC50分别为12nM和4200nM。
CAS:1936421-41-8
分子式:C27H32F2N6O2
分子量:510.58
纯度:98%
存储:Store at -20°C

Background:

GNE-049 is a highly potent and selective CBP inhibitor with an IC50 of 1.1 nM in TR-FRET assay. GNE-049 also inhibits BRET and BRD4(1) with IC50s of 12 nM and 4200 nM, respectively.


GNE-049 is selected for further profiling as it has the best balance of liver microsomes (LM) stability, selectivity, and cellular potency GNE-049 has excellent potency in the BRET cellular assay and, in an orthogonal measure of the target engagement, GNE-049 is shown to inhibit the expression of MYC (MV4-11 cell line) with an EC50 of 14 nM[1].


GNE-049 demonstrates acceptable PK in mouse, rat, dog, and monkey. Determination of potency versus a selection of bromodomains revealed that GNE-049 is selective for CBP/P300 and, importantly, quite selective (3820-fold) over BRD4(1). GNE-049 is further evaluated in a rat single dose (30-250 mg/kg QD) toxicokinetic study. Adverse central nervous system (CNS)-related signs (e.g., marked hyperactivity and vocalization) are observed in several of the rats at the 250 mg/kg dose level. Furthermore, at the 250 mg/kg dose level, the ratio of the unbound drug concentration in brain to unbound drug concentration in plasma (Kp,uu) 3 h post dose is determined to be 0.43, indicating that GNE-049 is penetrating into the CNS and potentially resulting in the observed toxicity[1].


[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.