期刊
TRENDS IN PHARMACOLOGICAL SCIENCES
卷 36, 期 3, 页码 137-144出版社
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tips.2015.01.001
关键词
PLD1; PLD2; small-molecule inhibitors; cancer; thrombosis; autoimmune disease
资金
- NIGMS NIH HHS [R01 GM084251, R01 GM100109] Funding Source: Medline
The phospholipase D (PLD) lipid-signaling enzyme superfamily has long been studied for its roles in cell communication and a wide range of cell biological processes. With the advent of loss-of-function genetic mouse models that have revealed that PLD1 and PLD2 ablation is overtly tolerable, small-molecule PLD1/2 inhibitors that do not cause unacceptable clinical toxicity, a PLD2 polymorphism that has been linked to altered physiology, and growing delineation of processes that are subtly altered in mice lacking PLD1/2 activity, the stage is being set for assessment of PLD1/2 inhibition for therapeutic purposes. Based on findings to date, PLD1/2 inhibition may be of more utility in acute rather than chronic settings, although this generalization will depend on the specific risks and benefits in each disease setting.
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