title: 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.
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
authors: Yanyang
authors: Y
authors: Wu
authors: Xin
authors: X
authors: Wang
authors: Haijing
authors: H
authors: Guo
authors: Bo
authors: B
authors: Zhang
authors: Xiao-Bo
authors: XB
authors: Zhang
authors: Zhang-Jie
authors: ZJ
authors: Shi
authors: Li
authors: L
authors: Yu
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004705:Endocytosis / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D054852:Small Molecule Libraries / Q000494:pharmacology
chemical_list: D000225:Adenine; D000255:Adenosine Triphosphate; D049452:Green Fluorescent Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D046988:Proteasome Endopeptidase Complex; D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries; C025946:3-methyladenine
keywords: 3-MA; autophagy; derivatives; inhibitor; synthesis