pf-8380 and Neoplasms

pf-8380 has been researched along with Neoplasms* in 3 studies

Other Studies

3 other study(ies) available for pf-8380 and Neoplasms

ArticleYear
Design, synthesis and promising anti-tumor efficacy of novel imidazo[1,2-a]pyridine derivatives as potent autotaxin allosteric inhibitors.
    European journal of medicinal chemistry, 2022, Jun-05, Volume: 236

    Aiming to track the potential antitumor effect of novel allosteric autotaxin (ATX) inhibitors, a hybrid strategy was utilized by merging ATX inhibitors PF-8380 and GLPG1690, while the piperazinyl group in GLPG1690 was replaced with benzene ring to furnish imidazo[1,2-a]pyridine derivatives 10ã10k. Based on ATX enzymatic assay, we further changed the substituents within benzyl carbamate moiety and tuned the carbamate linker to urea group. Delightfully, compound 10c bearing a N-hydroxyethyl piperazinyl group was identified as the optimal ATX inhibitor with an IC

    Topics: Animals; Carbamates; Cell Line, Tumor; Dose-Response Relationship, Drug; Humans; Mice; Neoplasms; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Pyridines; RAW 264.7 Cells; Structure-Activity Relationship

2022
Structure-Based Design of a Novel Class of Autotaxin Inhibitors Based on Endogenous Allosteric Modulators.
    Journal of medicinal chemistry, 2022, 04-28, Volume: 65, Issue:8

    Autotaxin (ATX) facilitates the hydrolysis of lysophosphatidylcholine to lysophosphatidic acid (LPA), a bioactive phospholipid, which facilitates a diverse range of cellular effects in multiple tissue types. Abnormal LPA expression can lead to the progression of diseases such as cancer and fibrosis. Previously, we identified a potent ATX steroid-derived hybrid (partially orthosteric and allosteric) inhibitor which did not form interactions with the catalytic site. Herein, we describe the design, synthesis, and biological evaluation of a focused library of novel steroid-derived analogues targeting the bimetallic catalytic site, representing an entirely unique class of ATX inhibitors of type V designation, which demonstrate significant pathway-relevant biochemical and phenotypic biological effects. The current compounds modulated LPA-mediated ATX allostery and achieved indirect blockage of LPA

    Topics: Chemotaxis; Humans; Hydrolysis; Lysophosphatidylcholines; Lysophospholipids; Neoplasms; Phosphoric Diester Hydrolases; Signal Transduction

2022
Discovery of potent inhibitors of the lysophospholipase autotaxin.
    Bioorganic & medicinal chemistry letters, 2016, 11-15, Volume: 26, Issue:22

    The autotaxin-lysophosphatidic acid (ATX-LPA) axis has been implicated in several disease conditions including inflammation, fibrosis and cancer. This makes ATX an attractive drug target and its inhibition may lead to useful therapeutic agents. Through a high throughput screen (HTS) we identified a series of small molecule inhibitors of ATX which have subsequently been optimized for potency, selectivity and developability properties. This has delivered drug-like compounds such as 9v (CRT0273750) which modulate LPA levels in plasma and are suitable for in vivo studies. X-ray crystallography has revealed that these compounds have an unexpected binding mode in that they do not interact with the active site zinc ions but instead occupy the hydrophobic LPC pocket extending from the active site of ATX together with occupying the LPA 'exit' channel.

    Topics: Animals; Antineoplastic Agents; Crystallography, X-Ray; Enzyme Inhibitors; Humans; Lysophospholipase; Lysophospholipids; Mice; Molecular Docking Simulation; Molecular Targeted Therapy; Neoplasms; Phosphoric Diester Hydrolases; Pyridines

2016