Ligand-based virtual screening identifies a family of selective cannabinoid receptor 2 agonists.
Ligand-based virtual screening identifies a family of selective cannabinoid receptor 2 agonists.
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DOI：
10.1016/j.bmc.2014.11.002
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发表时间：
2015-01-01
影响因子：
3.5
通讯作者：
Russell AJ
中科院分区：
文献类型：
--
作者：
Gianella-Borradori M;Christou I;Bataille CJ;Cross RL;Wynne GM;Greaves DR;Russell AJ
大麻素受体2（CB2R）与炎症的调节有关，选择性受体激活已被提出作为治疗一系列炎症性疾病如动脉粥样硬化和关节炎的靶点。为了鉴定具有适当的物理化学和ADME性质的选择性CB2R激动剂用于将来的体内评价，我们首先进行了基于配体的虚拟筛选。随后的药物化学优化研究导致了一类新的选择性CB2R激动剂的鉴定。几个实施例显示出对CB2R的高水平活性（EC50 < 200 nM）和结合亲和力（Ki < 200 nM），并且对CB1R没有可检测的活性。最有希望的实例DIAS 2在针对一组GPCR和激酶进行评价时，也显示出有利的体外代谢稳定性和吸收特性以及干净的选择性特征沿着。
The cannabinoid receptor 2 (CB2R) has been linked with the regulation of inflammation, and selective receptor activation has been proposed as a target for the treatment of a range of inflammatory diseases such as atherosclerosis and arthritis. In order to identify selective CB2R agonists with appropriate physicochemical and ADME properties for future evaluation in vivo, we first performed a ligand-based virtual screen. Subsequent medicinal chemistry optimisation studies led to the identification of a new class of selective CB2R agonists. Several examples showed high levels of activity (EC50 < 200 nM) and binding affinity (Ki < 200 nM) for the CB2R, and no detectable activity at the CB1R. The most promising example, DIAS2, also showed favourable in vitro metabolic stability and absorption properties along with a clean selectivity profile when evaluated against a panel of GPCRs and kinases.
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影响因子：
5.6
作者：
Hawkins, Paul C. D.;Nicholls, Anthony
通讯作者：
Nicholls, Anthony
人体免疫组织和白细胞亚群中枢和外周大麻素受体的表达
DOI：
10.1111/j.1432-1033.1995.tb20780.x
发表时间：
1995-08-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
GALIEGUE, S;MARY, S;CASELLAS, P
通讯作者：
CASELLAS, P
影响因子：
7.3
作者：
Giblin, Gerard M. P.;O'Shaughnessy, Celestine T.;Green, Richard
通讯作者：
Green, Richard
影响因子：
2
作者：
El Ashry, ESH;Ramadan, ES;Hagar, M
通讯作者：
Hagar, M
影响因子：
5
作者：
Hosohata, Y;Quock, RM;Yamamura, HI
通讯作者：
Yamamura, HI