Identification of natural products as selective PTP1B inhibitors via virtual screening
| Autor: | Yang Ying, Zhiyan Xiao, Fei Ye, Jin-Ying Tian |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Drug Evaluation
Preclinical Protein tyrosine phosphatase Computational biology 01 natural sciences Biochemistry chemistry.chemical_compound Structure-Activity Relationship Drug Discovery Humans Enzyme Inhibitors Molecular Biology chemistry.chemical_classification Protein Tyrosine Phosphatase Non-Receptor Type 1 Virtual screening Biological Products Natural product Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Drug discovery Organic Chemistry Ligand (biochemistry) Protein Tyrosine Phosphatase 1B Recombinant Proteins 0104 chemical sciences 010404 medicinal & biomolecular chemistry Enzyme Identification (biology) hormones hormone substitutes and hormone antagonists |
| Zdroj: | Bioorganic chemistry. 98 |
| ISSN: | 1090-2120 |
| Popis: | Protein tyrosine phosphatase 1B (PTP1B) is emerging as a promising yet challenging target for drug discovery. To identify natural products as new prototypes for PTP1B inhibitors, we employed a hierarchical protocol combining ligand-based and structure-based approaches for virtual screening against natural product libraries. Twenty-six compounds were prioritized for enzymatic evaluation against PTP1B, and ten of them were recognized as potent PTP1B inhibitors with IC50 values at the micromolar level. Notably, nine compounds demonstrated evident selectivity to PTP1B over four other PTPs, including the most homologous T-cell protein tyrosine phosphatase (TCPTP). The results implicated that the structural uniqueness of the natural products might be a potential solution to the selectivity issue associated with the target PTP1B. |
| Databáze: | OpenAIRE |
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