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Several years after its isolation from melanoma cells, an increasing body of experimental evidence has established the involvement of Autotaxin (ATX) in the pathogenesis of several diseases. ATX, an extracellular enzyme responsible for the hydrolysis of lysophosphatidylcholine (LPC) into the bioactive lipid lysophosphatidic acid (LPA), is overexpressed in a variety of human metastatic cancers and is strongly implicated in chronic inflammation and liver toxicity, fibrotic diseases, and thrombosis. Accordingly, the ATX‐LPA signaling pathway is considered a tractable target for therapeutic intervention substantiated by the multitude of research campaigns that have been successful in identifying ATX inhibitors by both academia and industry. Furthermore, from a therapeutic standpoint, the entry and the so far promising results of the first ATX inhibitor in advanced clinical trials against idiopathic pulmonary fibrosis (IPF) lends support to the viability of this approach, bringing it to the forefront of drug discovery efforts. The present review article aims to provide a comprehensive overview of the most important series of ATX inhibitors developed so far. Special weight is lent to the design, structure activity relationship and mode of binding studies carried out, leading to the identification of advanced leads. The most significant in vitro and in vivo pharmacological results of these advanced leads are also summarized. Lastly, the development of the first ATX inhibitor entered in clinical trials accompanied by its phase 1 and 2a clinical trial data is disclosed. [ABSTRACT FROM AUTHOR]

trans-2-Phencylcyclopropylamine (2- PCPA), a potent, clinically used antidepressant, affects monoamine neurotransmitter levels by inhibiting the main metabolizing enzymes, monoamine oxidases ( MAOs). However, the antidepressant action of this compound was not fully explained by its effects on MAOs due to its wide variety of biological effects. 2- PCPA also affects depression-associated pathophysiological pathways, and linked with increased levels of trace amines in brain, upregulation of GABAB receptors (where GABA is gamma amino butyric acid), modulation of phospholipid metabolism, and interference with various cytochrome P450 ( CYP) enzymes. Consequently, despite its adverse effects and limited clinical applicability, 2- PCPA has attracted interest as a structural scaffold for the development of mechanism-based inhibitors of various enzymes, including lysine-specific demethylase 1 ( LSD1), which is a possible target for cancer chemotherapy. In the recent years, many reports have appeared in the literature based on 2- PCPA scaffold and their potential medicinal implications. This review mainly focuses on the medicinal chemistry aspects including drug design, structure-activity relationships ( SAR), biological and biochemical properties, and mechanism of actions of 2- PCPA and its derivatives. Furthermore, we also highlight recent advance in this area and discuss their future applications for beneficial therapeutic effects. [ABSTRACT FROM AUTHOR]