PMID- 31490104
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20220531
IS  - 1538-0254 (Electronic)
IS  - 0739-1102 (Linking)
VI  - 38
IP  - 13
DP  - 2020 Aug
TI  - Design, synthesis, biological evaluation and molecular dynamics studies of 
      4-thiazolinone derivatives as protein tyrosine phosphatase 1B (PTP1B) inhibitors.
PG  - 3814-3824
LID - 10.1080/07391102.2019.1664333 [doi]
AB  - Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin 
      signaling pathway, and more and more studies have shown that it is a potential 
      target for the treatment of type 2 diabetes mellitus (T2DM). In this study, 17 
      new 4-thiazolinone derivatives were designed and synthesized as novel PTP1B 
      inhibitors, and ADMET prediction confirmed that these compounds were to be 
      drug-like. In vitro enzyme activity experiments were performed on these 
      compounds, and it was found that a plurality of compounds had good inhibitory 
      activity and high selectivity against PTP1B protein. Among them, compound 7p 
      exhibited the best inhibitory activity with an IC(50) of 0.92 muM. The binding 
      mode of compound 7p and PTP1B protein was explored, revealing the reason for its 
      high efficiency. In addition, molecular dynamics simulations for the PTP1B(WT) 
      and PTP1B(comp#7p) systems revealed the effects of compound 7p on PTP1B protein 
      at the molecular level. In summary, the study reported for the first time that 
      4-thiazolinone derivatives as a novel PTP1B inhibitor had good inhibitory 
      activity and selectivity for the treatment of T2DM, providing more options for 
      the development of PTP1B inhibitors. AbbreviationsBBBblood-brain 
      barrierCDC25Bcell division cycle 25 homolog BCYP2D6Cytochrome P450 2D6 
      bindingDCCMdynamic cross-correlation mapDSDiscovery StudioH bondhydrogen 
      bondHIAhuman intestinal absorptionLARleukocyte antigen-related 
      phosphataseMDmolecular dynamicsMEG-2maternal-effect germ-cell defective 
      2MM-PBSAmolecular mechanics Poisson Boltzmann surface area)PCAprincipal component 
      analysisPDBProtein Data BankpNPPp-nitrophenyl phosphatePPBplasma protein 
      bindingPTP1Bprotein tyrosine phosphotase 1BRMSDroot mean square deviationRMSFroot 
      mean square fluctuationSHP-1src homologous phosphatase-1SHP-2src homologous 
      phosphatase-2SPCsingle-point chargeTCPTPT cell protein tyrosine 
      phosphataseT2DMType 2 diabetes mellitusVDWvan der WaalsCommunicated by Ramaswamy 
      H. Sarma.
FAU - Liu, Wen-Shan
AU  - Liu WS
AD  - Tianjin Key Laboratory on Technologies Enabling Development of Clinical 
      Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical 
      University, Tianjin, China.
FAU - Wang, Rui-Rui
AU  - Wang RR
AD  - Tianjin Key Laboratory on Technologies Enabling Development of Clinical 
      Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical 
      University, Tianjin, China.
FAU - Yue, Hai
AU  - Yue H
AD  - Inner Mongolia Institute for Drug Control, Huhhot, Inner Mongolia, China.
FAU - Zheng, Zhi-Hui
AU  - Zheng ZH
AD  - New Drug Research & Development Center of North China Pharmaceutical Group 
      Corporation, National Microbial Medicine Engineering & Research Center, Hebei 
      Industry Microbial Metabolic Engineering & Technology Research Center, Key 
      Laboratory for New Drug Screening Technology of Shijiazhuang City, Shijiazhuang, 
      Hebei, China.
FAU - Lu, Xin-Hua
AU  - Lu XH
AD  - New Drug Research & Development Center of North China Pharmaceutical Group 
      Corporation, National Microbial Medicine Engineering & Research Center, Hebei 
      Industry Microbial Metabolic Engineering & Technology Research Center, Key 
      Laboratory for New Drug Screening Technology of Shijiazhuang City, Shijiazhuang, 
      Hebei, China.
FAU - Wang, Shu-Qing
AU  - Wang SQ
AD  - Tianjin Key Laboratory on Technologies Enabling Development of Clinical 
      Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical 
      University, Tianjin, China.
FAU - Dong, Wei-Li
AU  - Dong WL
AD  - Tianjin Key Laboratory on Technologies Enabling Development of Clinical 
      Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical 
      University, Tianjin, China.
FAU - Wang, Run-Ling
AU  - Wang RL
AD  - Tianjin Key Laboratory on Technologies Enabling Development of Clinical 
      Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical 
      University, Tianjin, China.
LA  - eng
PT  - Journal Article
DEP - 20190919
PL  - England
TA  - J Biomol Struct Dyn
JT  - Journal of biomolecular structure & dynamics
JID - 8404176
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Insulin)
RN  - EC 3.1.3.48 (PTPN1 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1)
SB  - IM
MH  - Diabetes Mellitus, Type 2
MH  - *Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - Insulin
MH  - Molecular Docking Simulation
MH  - Molecular Dynamics Simulation
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 1/*antagonists & inhibitors
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - PTP1B inhibitor
OT  - T2DM
OT  - activity
OT  - molecular docking
OT  - molecular dynamics simulation
EDAT- 2019/09/07 06:00
MHDA- 2021/06/22 06:00
CRDT- 2019/09/07 06:00
PHST- 2019/09/07 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2019/09/07 06:00 [entrez]
AID - 10.1080/07391102.2019.1664333 [doi]
PST - ppublish
SO  - J Biomol Struct Dyn. 2020 Aug;38(13):3814-3824. doi: 
      10.1080/07391102.2019.1664333. Epub 2019 Sep 19.