2. Academic Validation
  3. Regulation of protein phosphorylation by PTPN2 and its small-molecule inhibitors/degraders as a potential disease treatment strategy

Regulation of protein phosphorylation by PTPN2 and its small-molecule inhibitors/degraders as a potential disease treatment strategy

  • Eur J Med Chem. 2024 Nov 5:277:116774. doi: 10.1016/j.ejmech.2024.116774.
Dawei Wang 1,  Wenmu Wang 1,  Mingge Song 1,  Yishi Xie 1,  Wenbin Kuang 2,  Peng Yang 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
  • 2 State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address: [email protected].
  • 3 State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China; Institute of Innovative Drug Discovery and Development, China Pharmaceutical University, Nanjing 211198, China. Electronic address: [email protected].
PMID: 39178726 DOI: 10.1016/j.ejmech.2024.116774
Abstract

Protein tyrosine Phosphatase nonreceptor type 2 (PTPN2) is an enzyme that dephosphorylates proteins with tyrosine residues, thereby modulating relevant signaling pathways in vivo. PTPN2 acts as tumor suppressor or tumor promoter depending on the context. In some cancers, such as colorectal, and lung Cancer, PTPN2 defects could impair the protein tyrosine kinase pathway, which is often over-activated in Cancer cells, and inhibit tumor development and progression. However, PTPN2 can also suppress tumor immunity by regulating immune cells and cytokines. The structure, functions, and substrates of PTPN2 in various tumor cells were reviewed in this paper. And we summarized the research status of small molecule inhibitors and degraders of PTPN2. It also highlights the potential opportunities and challenges for developing PTPN2 inhibitors as Anticancer drugs.

Keywords

PTPN2; Regulatory mechanisms; Small molecule inhibitors; Substrates; Tumors.

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