| Autor: |
Mengxia Sun, Chi Zhang, Dexin Sui, Canchai Yang, Dohun Pyeon, Xuefei Huang, Jian Hu |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Chemistry (Weinheim an der Bergstrasse, Germany). |
| ISSN: |
1521-3765 |
| Popis: |
Phosphatidylinositol phosphate kinases (PIPKs) produce lipid signaling molecules and have been attracting increasing attention as drug targets for cancer, neurodegenerative diseases, and viral infection. Given the potential cross-inhibition of kinases and other ATP-utilizing enzymes by ATP-competitive inhibitors, targeting the unique lipid substrate binding site represents a superior strategy for PIPK inhibition. Here, by taking advantage of the nearly identical stereochemistry between myo-inositol and D-galactose, we designed and synthesized a panel of D-galactosyl lysophospholipids, one of which was found to be a selective substrate of phosphatidylinositol 4-phosphate 5-kinase. Derivatization of this compound led to the discovery of a human PIKfyve inhibitor with an apparent IC |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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