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Synthesis and screening of 3-MA derivatives for autophagy inhibitors.

ABSTRACT: Autophagy is a conserved degradation process, which plays important pathophysiological roles. The lack of effective inhibitors of autophagy has been an obstacle in both basic research and understanding the physiological role of autophagy in disease manifestation. The most widely used inhibitor, 3-methyladenine (3-MA), is poorly soluble at room temperature and is effective only at high concentrations. In this study, we synthesized a library of small compounds by chemically modifying 3-MA and screened this library for autophagy inhibitors. Three 3-MA derivatives generated through this approach showed improved solubility and effectiveness in inhibiting autophagy. We demonstrated that chemical modification of an existing autophagy inhibitor is an effective method to generate improved autophagy inhibitors.

SUBMITTER: Wu Y

PROVIDER: S-EPMC3627673 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Synthesis and screening of 3-MA derivatives for autophagy inhibitors.

Wu Yanyang Y Wang Xin X Guo Haijing H Zhang Bo B Zhang Xiao-Bo XB Shi Zhang-Jie ZJ Yu Li L

Autophagy 20130214 4

Autophagy is a conserved degradation process, which plays important pathophysiological roles. The lack of effective inhibitors of autophagy has been an obstacle in both basic research and understanding the physiological role of autophagy in disease manifestation. The most widely used inhibitor, 3-methyladenine (3-MA), is poorly soluble at room temperature and is effective only at high concentrations. In this study, we synthesized a library of small compounds by chemically modifying 3-MA and scre ...[more]

PMID: 23412639

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