2. Academic Validation
  3. Discovery of novel, high potent, ABC type PTP1B inhibitors with TCPTP selectivity and cellular activity

Discovery of novel, high potent, ABC type PTP1B inhibitors with TCPTP selectivity and cellular activity

  • Eur J Med Chem. 2016 Aug 8;118:27-33. doi: 10.1016/j.ejmech.2016.04.014.
Peihong Liu 1,  Yongli Du 2,  Lianhua Song 1,  Jingkang Shen 3,  Qunyi Li 4
Affiliations

Affiliations

  • 1 School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology, 3501 Daxue Road, Jinan 250353, China.
  • 2 School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology, 3501 Daxue Road, Jinan 250353, China. Electronic address: ylduyjs@163.com.
  • 3 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
  • 4 Clinical Pharmacy Laboratory, Huashan Hospital, Fudan University, 12 Wu Lu Mu Qi M Road, Shanghai 200040, China. Electronic address: qyli1234@163.com.
PMID: 27123900 DOI: 10.1016/j.ejmech.2016.04.014
Abstract

Protein tyrosine Phosphatase 1B (PTP1B) as a key negative regulator of both Insulin and Leptin receptor pathways has been an attractive therapeutic target for the treatment of type 2 diabetes mellitus (T2DM) and obesity. With the goal of enhancing potency and selectivity of the PTP1B inhibitors, a series of methyl salicylate derivatives as ABC type PTP1B inhibitors (P1-P7) were discovered. More importantly, compound P6 exhibited high potent inhibitory activity (IC50 = 50 nM) for PTP1B with 15-fold selectivity over T-cell PTPase (TCPTP). Further studies on cellular activities revealed that compound P6 could enhance insulin-mediated Insulin Receptor β (IRβ) phosphorylation and insulin-stimulated glucose uptake.

Keywords

ABC type PTP1B inhibitor; Methyl salicylate derivatives; Type 2 diabetes mellitus.

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