Status of research on natural protein tyrosine phosphatase 1B inhibitors as potential antidiabetic agents: Update

Liu, Zhenyang; Gao, Hongwei; Zhao, Zhidan; Huang, Mengrui; Wang, Shengnan; Zhan, Jianming

doi:10.1016/j.biopha.2022.113990

Cited by 16 publications

(4 citation statements)

References 138 publications

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“…Allosteric PTPN11 inhibitors appear to have an acceptable toxicity profile in stage 1 clinical trials, although further dose escalation studies are ongoing [49,126]. Of note, trials assessing the efficacy of several PTPN1 inhibitors for the treatment of type 2 diabetes were halted due to low efficacy and toxicities, including vomiting and diarrhoea [127,128]. Pre-clinical studies suggest low toxicity of novel dual PTPN1/2 inhibitors in mice; it is hoped that similar safety profiles are revealed in ongoing clinical trials [31].…”

Section: Discussionmentioning

confidence: 99%

Targeting Protein Tyrosine Phosphatases to Improve Cancer Immunotherapies

Salmond

2024

Cells

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Advances in immunotherapy have brought significant therapeutic benefits to many cancer patients. Nonetheless, many cancer types are refractory to current immunotherapeutic approaches, meaning that further targets are required to increase the number of patients who benefit from these technologies. Protein tyrosine phosphatases (PTPs) have long been recognised to play a vital role in the regulation of cancer cell biology and the immune response. In this review, we summarize the evidence for both the pro-tumorigenic and tumour-suppressor function of non-receptor PTPs in cancer cells and discuss recent data showing that several of these enzymes act as intracellular immune checkpoints that suppress effective tumour immunity. We highlight new data showing that the deletion of inhibitory PTPs is a rational approach to improve the outcomes of adoptive T cell-based cancer immunotherapies and describe recent progress in the development of PTP inhibitors as anti-cancer drugs.

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Section: Discussionmentioning

confidence: 99%

Targeting Protein Tyrosine Phosphatases to Improve Cancer Immunotherapies

Salmond

2024

Cells

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“…Moreover, antisense oligonucleotide (ASO) inhibitors selectively bind specific sequences of PTP1B mRNA and reduce the expression of PTP1B, improving the poor membrane permeability [89]. Although improvement strategies continue to be proposed, the only PTP1B inhibitors that have entered clinical trials to date are ertiprotafib (a non-competitive pleiotropic inhibitor), ISIS-113715 (an ASO inhibitor), trodusquemine (an allosteric inhibitor), and JTT-551 (a hybrid inhibitor); however, all the trials were eventually discontinued due to the emergence of adverse side effects and low specificity [92,93].…”

Section: Protein Tyrosine Phosphatase 1b (Ptp1b)mentioning

confidence: 99%

“…Currently, researchers are paying close attention to natural products. Natural products isolated from natural plants have good biocompatibility, low side effects, synergistic effects on a wide range of diseases, and are of low cost with great medicinal value [92]. Many natural products, including phenols, terpenoids, flavonoids, and alkaloids, have been identified as potent PTP1B inhibitors [94].…”

Section: Protein Tyrosine Phosphatase 1b (Ptp1b)mentioning

confidence: 99%

Advances in Research on Type 2 Diabetes Mellitus Targets and Therapeutic Agents

Su,

Luo,

et al. 2023

IJMS

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Diabetes mellitus is a chronic multifaceted disease with multiple potential complications, the treatment of which can only delay and prolong the terminal stage of the disease, i.e., type 2 diabetes mellitus (T2DM). The World Health Organization predicts that diabetes will be the seventh leading cause of death by 2030. Although many antidiabetic medicines have been successfully developed in recent years, such as GLP-1 receptor agonists and SGLT-2 inhibitors, single-target drugs are gradually failing to meet the therapeutic requirements owing to the individual variability, diversity of pathogenesis, and organismal resistance. Therefore, there remains a need to investigate the pathogenesis of T2DM in more depth, identify multiple therapeutic targets, and provide improved glycemic control solutions. This review presents an overview of the mechanisms of action and the development of the latest therapeutic agents targeting T2DM in recent years. It also discusses emerging target-based therapies and new potential therapeutic targets that have emerged within the last three years. The aim of our review is to provide a theoretical basis for further advancement in targeted therapies for T2DM.

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“…However, developing PTP1B inhibitors remains challenging because they often possess a highly negatively charged group to interact at the catalytic site, which impairs their pharmacokinetic properties. Similarly, the highly conserved catalytic domain of the PTP’s family promotes these inhibitors to be less selective, thus increasing their toxicity [ 41 , 42 , 43 , 44 ]. Hence, currently, there are no approved anti-diabetic drugs that target PTP1B activity.…”

Section: Introductionmentioning

confidence: 99%

Anti-Diabetic Activity of Glycyrrhetinic Acid Derivatives FC-114 and FC-122: Scale-Up, In Silico, In Vitro, and In Vivo Studies

Álvarez-Almazán,

Solís-Domínguez,

Duperou-Luna

et al. 2023

IJMS

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Type 2 diabetes (T2D) is one of the most common diseases and the 8th leading cause of death worldwide. Individuals with T2D are at risk for several health complications that reduce their life expectancy and quality of life. Although several drugs for treating T2D are currently available, many of them have reported side effects ranging from mild to severe. In this work, we present the synthesis in a gram-scale as well as the in silico and in vitro activity of two semisynthetic glycyrrhetinic acid (GA) derivatives (namely FC-114 and FC-122) against Protein Tyrosine Phosphatase 1B (PTP1B) and α-glucosidase enzymes. Furthermore, the in vitro cytotoxicity assay on Human Foreskin fibroblast and the in vivo acute oral toxicity was also conducted. The anti-diabetic activity was determined in streptozotocin-induced diabetic rats after oral administration with FC-114 or FC-122. Results showed that both GA derivatives have potent PTP1B inhibitory activity being FC-122, a dual PTP1B/α-glucosidase inhibitor that could increase insulin sensitivity and reduce intestinal glucose absorption. Molecular docking, molecular dynamics, and enzymatic kinetics studies revealed the inhibition mechanism of FC-122 against α-glucosidase. Both GA derivatives were safe and showed better anti-diabetic activity in vivo than the reference drug acarbose. Moreover, FC-114 improves insulin levels while decreasing LDL and total cholesterol levels without decreasing HDL cholesterol.

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Status of research on natural protein tyrosine phosphatase 1B inhibitors as potential antidiabetic agents: Update

Cited by 16 publications

References 138 publications

Targeting Protein Tyrosine Phosphatases to Improve Cancer Immunotherapies

Targeting Protein Tyrosine Phosphatases to Improve Cancer Immunotherapies

Advances in Research on Type 2 Diabetes Mellitus Targets and Therapeutic Agents

Anti-Diabetic Activity of Glycyrrhetinic Acid Derivatives FC-114 and FC-122: Scale-Up, In Silico, In Vitro, and In Vivo Studies

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