PMID- 37302637
OWN - NLM
STAT- MEDLINE
DCOM- 20230619
LR  - 20230619
IS  - 1879-0003 (Electronic)
IS  - 0141-8130 (Linking)
VI  - 243
DP  - 2023 Jul 15
TI  - Identification of natural product inhibitors of PTP1B based on high-throughput 
      virtual screening strategy: In silico, in vitro and in vivo studies.
PG  - 125292
LID - S0141-8130(23)02186-4 [pii]
LID - 10.1016/j.ijbiomac.2023.125292 [doi]
AB  - Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of the 
      insulin signaling pathway, which is a potential therapeutic target for the 
      treatment of type 2 diabetes mellitus (T2DM). In this study, we identified 
      several PTP1B inhibitors with high activity by using high-throughput virtual 
      screening and in vitro enzyme inhibition activity verification strategies. Among 
      them, baicalin was first reported as a selective mixed inhibitor of PTP1B, with 
      IC(50) value of 3.87 +/- 0.45 muM, and its inhibitory activity against homologous 
      proteins TCPTP, SHP2, and SHP1 exceeded 50 muM. Molecular docking study found that 
      baicalin and PTP1B could bind stably, and revealed that baicalin had a dual 
      inhibitory effect. Cell experiments showed that baicalin was almost non-toxic and 
      could significantly enhance the phosphorylation of IRS-1 in C2C12 myotube cells. 
      Animal experiments showed that baicalin could significantly reduce the blood 
      sugar of STZ-induced diabetic mice models, and had a liver protective effect. In 
      conclusion, this study can provide new ideas for the development of PTP1B 
      selective inhibitors.
CI  - Copyright (c) 2023. Published by Elsevier B.V.
FAU - Zhao, Ji-Feng
AU  - Zhao JF
AD  - Shandong Key Laboratory of Medicine and Health (Clinical Applied Pharmacology), 
      Department of Pharmacy, Affiliated Hospital of Weifang Medical University, 
      Weifang 261041, Shandong Province, China; Clinical Research Center, Affiliated 
      Hospital of Weifang Medical University, Weifang 261041, Shandong Province, China.
FAU - Li, Li-Hua
AU  - Li LH
AD  - Eye Center, Affiliated Hospital of Weifang Medical University, Weifang 261041, 
      Shandong Province, China; Clinical Research Center, Affiliated Hospital of 
      Weifang Medical University, Weifang 261041, Shandong Province, China.
FAU - Guo, Xiao-Jing
AU  - Guo XJ
AD  - Clinical Research Center, Affiliated Hospital of Weifang Medical University, 
      Weifang 261041, Shandong Province, China.
FAU - Zhang, Hai-Xia
AU  - Zhang HX
AD  - Shandong Key Laboratory of Medicine and Health (Clinical Applied Pharmacology), 
      Department of Pharmacy, Affiliated Hospital of Weifang Medical University, 
      Weifang 261041, Shandong Province, China.
FAU - Tang, Lin-Lin
AU  - Tang LL
AD  - Shandong Key Laboratory of Medicine and Health (Clinical Applied Pharmacology), 
      Department of Pharmacy, Affiliated Hospital of Weifang Medical University, 
      Weifang 261041, Shandong Province, China.
FAU - Ding, Chuan-Hua
AU  - Ding CH
AD  - Shandong Key Laboratory of Medicine and Health (Clinical Applied Pharmacology), 
      Department of Pharmacy, Affiliated Hospital of Weifang Medical University, 
      Weifang 261041, Shandong Province, China. Electronic address: dchh422@163.com.
FAU - Liu, Wen-Shan
AU  - Liu WS
AD  - Shandong Key Laboratory of Medicine and Health (Clinical Applied Pharmacology), 
      Department of Pharmacy, Affiliated Hospital of Weifang Medical University, 
      Weifang 261041, Shandong Province, China; Clinical Research Center, Affiliated 
      Hospital of Weifang Medical University, Weifang 261041, Shandong Province, China. 
      Electronic address: liuwenshan@wfmc.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230609
PL  - Netherlands
TA  - Int J Biol Macromol
JT  - International journal of biological macromolecules
JID - 7909578
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - 0 (Insulin)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1)
RN  - 0 (Enzyme Inhibitors)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Molecular Docking Simulation
MH  - Phosphoric Monoester Hydrolases
MH  - *Diabetes Mellitus, Experimental/drug therapy
MH  - Insulin/metabolism
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 1
MH  - Enzyme Inhibitors/metabolism
OTO - NOTNLM
OT  - Activity
OT  - Molecular docking
OT  - Natural product
OT  - PTP1B inhibitor
OT  - Selectivity
COIS- Declaration of competing interest The authors report no conflicts of interest in 
      this work.
EDAT- 2023/06/12 00:42
MHDA- 2023/06/19 13:08
CRDT- 2023/06/11 19:16
PHST- 2023/03/19 00:00 [received]
PHST- 2023/06/05 00:00 [revised]
PHST- 2023/06/07 00:00 [accepted]
PHST- 2023/06/19 13:08 [medline]
PHST- 2023/06/12 00:42 [pubmed]
PHST- 2023/06/11 19:16 [entrez]
AID - S0141-8130(23)02186-4 [pii]
AID - 10.1016/j.ijbiomac.2023.125292 [doi]
PST - ppublish
SO  - Int J Biol Macromol. 2023 Jul 15;243:125292. doi: 10.1016/j.ijbiomac.2023.125292. 
      Epub 2023 Jun 9.