ArticleJournal of medicinal chemistry2019
Discovery and Optimization of Selective and in Vivo Active Inhibitors of the Lysophosphatidylserine Lipase α/β-Hydrolase Domain-Containing 12 (ABHD12).
Article in Journal of medicinal chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Spatially Resolved Mapping of Monoacylglycerol Lipase Activity in the Brain.ACS chemical neuroscience · 2025Article
- Suppressing phagocyte activation by overexpressing the phosphatidylserine lipase ABHD12 preserves sarmopathic nerves.iScience · 2025Article
- Unique transcriptomic responses of rat and human alveolar macrophages in an in vitro model of overload with TiOParticle and fibre toxicology · 2025Article
- Impact of Psychological Stress and Spontaneous Tumour Regression on the Hippocampal Proteome in a Mouse Model of Breast Cancer.Journal of neurochemistry · 2025Article
- PHARC syndrome: an overview.Orphanet journal of rare diseases · 2024Review
- From Classical to Alternative Pathways of 2-Arachidonoylglycerol Synthesis: AlterAGs at the Crossroad of Endocannabinoid and Lysophospholipid Signaling.Molecules (Basel, Switzerland) · 2024Review
- Enhanced mapping of small-molecule binding sites in cells.Nature chemical biology · 2024Article
- Biomimetic Synthesis and Chemical Proteomics Reveal the Mechanism of Action and Functional Targets of Phloroglucinol Meroterpenoids.Journal of the American Chemical Society · 2024Article
- Probing the Interactions of Thiazole Abietane Inhibitors with the Human Serine Hydrolases ABHD16A and ABHD12.ACS medicinal chemistry letters · 2023Article
- Strategies for Competitive Activity-Based Protein Profiling in Small Molecule Inhibitor Discovery and Characterization.Israel journal of chemistry · 2023Article
- Increase in Cellular Lysophosphatidylserine Content Exacerbates Inflammatory Responses in LPS-Activated Microglia.Neurochemical research · 2022Article
- Discovering monoacylglycerol lipase inhibitors by a combination of fluorogenic substrate assay and activity-based protein profiling.Frontiers in pharmacology · 2022Article
- Role of the Endocannabinoid System in the Regulation of Intestinal Homeostasis.Cellular and molecular gastroenterology and hepatology · 2022Review
- The loss of enzymatic activity of the PHARC-associated lipase ABHD12 results in increased phagocytosis that causes neuroinflammation.The European journal of neuroscience · 2021Article
- α/β-Hydrolase Domain (ABHD) Inhibitors as New Potential Therapeutic Options against Lipid-Related Diseases.Journal of medicinal chemistry · 2021Review
- Functionalized Scout Fragments for Site-Specific Covalent Ligand Discovery and Optimization.ACS central science · 2021Article
- Endocannabinoid metabolism and transport as targets to regulate intraocular pressure.Experimental eye research · 2020Article
- The Lysophosphatidylserines-An Emerging Class of Signalling Lysophospholipids.The Journal of membrane biology · 2020Review
- Mapping the Neuroanatomy of ABHD16A, ABHD12, and Lysophosphatidylserines Provides New Insights into the Pathophysiology of the Human Neurological Disorder PHARC.Biochemistry · 2020Article
- ABHD12 and LPCAT3 Interplay Regulates a Lyso-phosphatidylserine-C20:4 Phosphatidylserine Lipid Network Implicated in Neurological Disease.Biochemistry · 2020Article
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Authors and funding
7 authors.
Funding
Abstract
ABHD12 is a membrane-bound hydrolytic enzyme that acts on the lysophosphatidylserine (lyso-PS) and lysophosphatidylinositol (lyso-PI) classes of immunomodulatory lipids. Human and mouse genetic studies point to a key role for the ABHD12-(lyso)-PS/PI pathway in regulating (neuro)immunological functions in both the central nervous system and periphery. Selective inhibitors of ABHD12 would offer valuable pharmacological probes to complement genetic models of ABHD12-regulated (lyso)-PS/PI metabolism and signaling. Here, we provide a detailed description of the discovery and activity-based protein profiling (ABPP) guided optimization of reversible thiourea inhibitors of ABHD12 that culminated in the identification of DO264 as a potent, selective, and in vivo active ABHD12 inhibitor. We also show that DO264, but not a structurally related inactive control probe (S)-DO271, augments inflammatory cytokine production from human THP-1 macrophage cells. The in vitro and in vivo properties of DO264 designate this compound as a suitable chemical probe for studying the biological functions of ABHD12-(lyso)-PS/PI pathways.
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