AI Article Synopsis
- Autotaxin (ATX) is being targeted for new liver disease treatments, and drug candidates were identified through high-throughput screening methods.
- Researchers synthesized a small molecule called KR-40795, designed to inhibit ATX's activity by binding to specific regions of the enzyme.
- KR-40795 effectively reduced collagen formation and lipid accumulation in liver cells, showcasing its potential to treat liver conditions like fibrosis and steatosis.
Article Abstract
Autotaxin (ATX) has emerged as a promising therapeutic target for liver diseases. In this study, we identified potential drug candidates through in silico high-throughput screening. Subsequently, we synthesized a series of small molecules, specifically KR-40795 (2c), a pyrrolidine-2,5-dione-based analogue that binds to the allosteric tunnel and hydrophobic pocket of ATX. This compound was designed to inhibit the enzymatic activity of ATX for the treatment of liver diseases. The inhibitory potency of KR-40795 was evaluated using a biochemical assay that measured the hydrolysis of a specific substrate (FS-3). Notably, KR-40795 demonstrated significant inhibition of both collagen formation and lipid accumulation in liver cells, suggesting its potential as a therapeutic agent for liver diseases, particularly fibrosis and steatosis.
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| http://dx.doi.org/10.1016/j.bmcl.2024.130006 | DOI Listing |
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