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

Biomed Pharmacother. 2023 Jan:157:113990. doi: 10.1016/j.biopha.2022.113990. Epub 2022 Nov 29.

Abstract

Protein tyrosine phosphatase 1B (PTP1B) is a crucial therapeutic target for multiple human diseases comprising type 2 diabetes (T2DM) and obesity because it is a seminal part of a negative regulator in both insulin and leptin signaling pathways. PTP1B inhibitors increase insulin receptor sensitivity and have the ability to cure insulin resistance-related diseases. However, the few PTP1B inhibitors that entered the clinic (Ertiprotafib, ISIS-113715, Trodusquemine, and JTT-551) were discontinued due to side effects or low selectivity. Molecules with broad chemical diversity extracted from natural products have been reported to be potent PTP1B inhibitors with few side effects. This article summarizes the recent PTP1B inhibitors extracted from natural products, clarifying the current research progress, and providing new options for designing new and effective PTP1B inhibitors.

Keywords: Inhibitor; Natural product; Protein tyrosine phosphatase 1B (PTP1B); Structure-activity relationship (SAR); Type 2 diabetes.

Publication types

  • Review

MeSH terms

  • Biological Products* / pharmacology
  • Biological Products* / therapeutic use
  • Diabetes Mellitus, Type 2* / drug therapy
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Insulin / metabolism
  • Insulin Resistance*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1

Substances

  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Hypoglycemic Agents
  • Insulin
  • Enzyme Inhibitors
  • Biological Products