ArticleJournal of medicinal chemistry2021
Discovery of Orally Bioavailable Purine-Based Inhibitors of the Low-Molecular-Weight Protein Tyrosine Phosphatase.
Article in Journal of medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 20 citations in OpenAlex.
- Targeting prostate tumor low-molecular weight tyrosine phosphatase for oxidation-sensitizing therapy.Science advances · 2024Article
- Article
- Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders.Nature reviews. Drug discovery · 2023Review
- Virtual Screening and Biological Evaluation of Novel Low Molecular Weight Protein Tyrosine Phosphatase Inhibitor for the Treatment of Insulin Resistance.Drug design, development and therapy · 2023Article
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Obesity-associated insulin resistance plays a central role in the pathogenesis of type 2 diabetes. A promising approach to decrease insulin resistance in obesity is to inhibit the protein tyrosine phosphatases that negatively regulate insulin receptor signaling. The low-molecular-weight protein tyrosine phosphatase (LMPTP) acts as a critical promoter of insulin resistance in obesity by inhibiting phosphorylation of the liver insulin receptor activation motif. Here, we report development of a novel purine-based chemical series of LMPTP inhibitors. These compounds inhibit LMPTP with an uncompetitive mechanism and are highly selective for LMPTP over other protein tyrosine phosphatases. We also report the generation of a highly orally bioavailable purine-based analogue that reverses obesity-induced diabetes in mice.
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Registered trials
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