Aiming drug discovery at lysophosphatidic acid targets.
Aiming drug discovery at lysophosphatidic acid targets.
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DOI：
10.1111/j.1476-5381.2010.00815.x
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发表时间：
2010-09
影响因子：
7.3
通讯作者：
Tigyi G
中科院分区：
文献类型：
--
作者：
Tigyi G
溶血磷脂酸(LPA，1-radyl-2-羟基-sn-甘油-3-磷酸)是脂类介体和第二信使家族的原型成员。LPA及其天然类似物与细胞表面的G蛋白偶联受体和细胞内的核激素受体相互作用。此外，还有几种酶利用LPA作为底物或将其作为产物产生，并受其调控。LPA存在于生物体液中，人们试图将其浓度和分子组成的变化与特定的疾病情况联系起来。通过它们的许多靶点，LPA家族的成员调控细胞的生存、凋亡、运动、形状、分化、基因转录、恶性转化等。本综述描述了LPA的生理和病理生理作用的任意方面，并试图将它们与选定的靶点联系起来。我们中的许多人现在相信，针对LPA生物合成和信号转导的疗法对于治疗癌症、纤维化和退行性疾病等毁灭性的人类疾病是可行的。然而，与这种多效性脂质相关的通路的成功靶向将取决于尚未开发的药物的未来发展。
Lysophosphatidic acid (LPA, 1-radyl-2-hydroxy-sn-glycero-3-phosphate) is the prototype member of a family of lipid mediators and second messengers. LPA and its naturally occurring analogues interact with G protein-coupled receptors on the cell surface and a nuclear hormone receptor within the cell. In addition, there are several enzymes that utilize LPA as a substrate or generate it as a product and are under its regulatory control. LPA is present in biological fluids, and attempts have been made to link changes in its concentration and molecular composition to specific disease conditions. Through their many targets, members of the LPA family regulate cell survival, apoptosis, motility, shape, differentiation, gene transcription, malignant transformation and more. The present review depicts arbitrary aspects of the physiological and pathophysiological actions of LPA and attempts to link them with select targets. Many of us are now convinced that therapies targeting LPA biosynthesis and signalling are feasible for the treatment of devastating human diseases such as cancer, fibrosis and degenerative conditions. However, successful targeting of the pathways associated with this pleiotropic lipid will depend on the future development of as yet undeveloped pharmacons.
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影响因子：
3.5
作者：
Bandoh, K;Aoki, J;Inoue, K
通讯作者：
Inoue, K
影响因子：
32.4
作者：
Angeli, V;Llodrá, J;Randolph, GJ
通讯作者：
Randolph, GJ
影响因子：
7.4
作者：
Ahn, Dong K.;Lee, Sang Y.;Bae, Yong C.
通讯作者：
Bae, Yong C.
DOI：
10.1073/pnas.97.24.13384
发表时间：
2000-11-21
影响因子：
11.1
作者：
Contos, JJA;Fukushima, N;Chun, J
通讯作者：
Chun, J
影响因子：
6.2
作者：
Caverzasio, J;Palmer, G;Bonjour, JP
通讯作者：
Bonjour, JP