PMID- 32422389
OWN - NLM
STAT- MEDLINE
DCOM- 20210301
LR  - 20210301
IS  - 1090-2120 (Electronic)
IS  - 0045-2068 (Linking)
VI  - 100
DP  - 2020 Jul
TI  - The antidiabetic drug lobeglitazone has the potential to inhibit PTP1B activity.
PG  - 103927
LID - S0045-2068(20)30040-7 [pii]
LID - 10.1016/j.bioorg.2020.103927 [doi]
AB  - Protein tyrosine phosphatase 1B (PTP1B) is considered a potential therapeutic 
      target for the treatment of type 2 diabetes mellitus (T2DM), since this enzyme 
      plays a significant role to down-regulate insulin and leptin signalling and its 
      over expression has been implicated in the development of insulin resistance, 
      T2DM and obesity. Some thiazolidinediones (TZD) derivatives have been reported as 
      promising PTP1B inhibitors with anti hyperglycemic effects. Recently, 
      lobeglitazone, a new TZD, was described as an antidiabetic drug that targets the 
      PPAR-gamma (peroxisome gamma proliferator-activated receptor) pathway, but no information 
      on its effects on PTP1B have been reported to date. We investigated the effects 
      of lobeglitazone on PTP1B activity in vitro. Surprisingly, lobeglitazone led to 
      moderate inhibition on PTP1B (IC(50) 42.8 +/- 3.8 microM) activity and to a 
      non-competitive reversible mechanism of action. As lobeglitazone inhibits PTP1B 
      activity in vitro, we speculate that it could also target PTP1B signalling 
      pathway in vivo and thus contribute to potentiate its antidiabetic effects.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Rocha, Ruth F
AU  - Rocha RF
AD  - Centro de Biologia Molecular Estrutural, Departamento de Bioquimica, Universidade 
      Federal de Santa Catarina, Campus Trindade, 88040-900 Florianopolis, SC, Brazil.
FAU - Rodrigues, Tiago
AU  - Rodrigues T
AD  - Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 
      Avenida Professor Egas Moniz, 1649-028 Lisbon, Portugal.
FAU - Menegatti, Angela C O
AU  - Menegatti ACO
AD  - Centro de Biologia Molecular Estrutural, Departamento de Bioquimica, Universidade 
      Federal de Santa Catarina, Campus Trindade, 88040-900 Florianopolis, SC, Brazil; 
      Universidade Federal do Piaui, CPCE, 64900-000 Bom Jesus, PI, Brazil. Electronic 
      address: angelamenegatti@yahoo.com.br.
FAU - Bernardes, Goncalo J L
AU  - Bernardes GJL
AD  - Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 
      Avenida Professor Egas Moniz, 1649-028 Lisbon, Portugal; Department of Chemistry, 
      University of Cambridge, Lensfield Road, CB2 1EW Cambridge, UK.
FAU - Terenzi, Hernan
AU  - Terenzi H
AD  - Centro de Biologia Molecular Estrutural, Departamento de Bioquimica, Universidade 
      Federal de Santa Catarina, Campus Trindade, 88040-900 Florianopolis, SC, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200511
PL  - United States
TA  - Bioorg Chem
JT  - Bioorganic chemistry
JID - 1303703
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Pyrimidines)
RN  - 0 (Thiazolidinediones)
RN  - EC 3.1.3.48 (PTPN1 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1)
RN  - MY89F08K5D (lobeglitazone)
SB  - IM
MH  - Enzyme Inhibitors/chemistry/metabolism/pharmacology
MH  - Humans
MH  - Hypoglycemic Agents/*chemistry/metabolism/pharmacology
MH  - Inhibitory Concentration 50
MH  - Kinetics
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 1/*antagonists & 
      inhibitors/metabolism
MH  - Pyrimidines/*chemistry/metabolism/pharmacology
MH  - Signal Transduction/drug effects
MH  - Thiazolidinediones/*chemistry/metabolism/pharmacology
OTO - NOTNLM
OT  - Lobeglitazone
OT  - Non-competitive inhibitors
OT  - PPAR-gamma
OT  - PTP1B
OT  - Thiazolidinediones
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/05/19 06:00
MHDA- 2021/03/02 06:00
CRDT- 2020/05/19 06:00
PHST- 2020/01/07 00:00 [received]
PHST- 2020/04/03 00:00 [revised]
PHST- 2020/05/08 00:00 [accepted]
PHST- 2020/05/19 06:00 [pubmed]
PHST- 2021/03/02 06:00 [medline]
PHST- 2020/05/19 06:00 [entrez]
AID - S0045-2068(20)30040-7 [pii]
AID - 10.1016/j.bioorg.2020.103927 [doi]
PST - ppublish
SO  - Bioorg Chem. 2020 Jul;100:103927. doi: 10.1016/j.bioorg.2020.103927. Epub 2020 
      May 11.