Abstract | Purpose: Methods: A virtual screening pipeline based on the X-ray co-crystal complex of LMPTP was constructed. Enzyme inhibition assay and cellular bioassay were used to evaluate the activity of screened compounds. Results: The screening pipeline rendered 15 potential hits from Specs chemical library. Enzyme inhibition assay identified compound F9 (AN-465/41163730) as a potential LMPTP inhibitor with a K i value of 21.5 ± 7.3 μM. Cellular bioassay showed F9 could effectively increase the glucose consumption of HepG2 cells as a result of releasing insulin resistance by regulating PI3K-Akt pathway. Conclusion: In summary, this study presents a versatile virtual screening pipeline for potential LMPTP inhibitor discovery and provides a novel-scaffold lead compound that is worthy of further modification to get more potent LMPTP inhibitors.
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Authors | Bo Feng, Xu Dong, Zhen Liu, Jie Zhang, Hongyu Liu, Yuan Xu |
Journal | Drug design, development and therapy
(Drug Des Devel Ther)
Vol. 17
Pg. 1191-1201
( 2023)
ISSN: 1177-8881 [Electronic] New Zealand |
PMID | 37113468
(Publication Type: Journal Article)
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Copyright | © 2023 Feng et al. |
Chemical References |
- Tyrosine
- Phosphatidylinositol 3-Kinases
- Enzyme Inhibitors
- Protein Tyrosine Phosphatases
- Protein Tyrosine Phosphatase, Non-Receptor Type 1
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Topics |
- Humans
- Molecular Weight
- Tyrosine
- Phosphatidylinositol 3-Kinases
- Enzyme Inhibitors
(pharmacology, chemistry)
- Protein Tyrosine Phosphatases
(metabolism)
- Insulin Resistance
- Obesity
- Protein Tyrosine Phosphatase, Non-Receptor Type 1
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