Therapeutic strategies for targeting PTP1B in diabetes

Montalibet, Jacqueline; Kennedy, Brian P.

doi:10.1016/j.ddstr.2005.05.002

Cited by 66 publications

(37 citation statements)

References 46 publications

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“…Compelling evidence indicates that PTP1B is involved in the regulation of leptin signalling by dephosphorylating the leptin receptor-associated Janus kinase 2 (JAK2). In vivo studies on leptin-deficient mice lacking PTP1B have shown moderate weight gain with normal food intake [5,6,18,19,24,25].…”

Section: Introductionmentioning

confidence: 99%

New 4-[(5-arylidene-2-arylimino-4-oxo-3-thiazolidinyl)methyl]benzoic acids active as protein tyrosine phosphatase inhibitors endowed with insulinomimetic effect on mouse C2C12 skeletal muscle cells

Ottanà

Maccari

Amuso

et al. 2012

European Journal of Medicinal Chemistry

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a b s t r a c tIn pursuing our research targeting the identification of potent inhibitors of PTP1B and LMW-PTP, we have identified new 4-[(5-arylidene-2-arylimino-4-oxo-3-thiazolidinyl)methyl]benzoic acids endowed with interesting in vitro inhibitory profiles. Most compounds proved to be inhibitors of PTP1B and LMW-PTP isoform IF1. The tested inhibitors also showed selectivity towards PTP1B over the closely related TC-PTP. These compounds were found to activate the insulin-mediated signalling on mouse C2C12 skeletal muscle cells by increasing the phosphorylation levels of the insulin receptor and promoting cellular 2-deoxyglucose uptake.Interestingly, 4-{[5-(4-benzyloxybenzylidene)-2-(4-trifluoromethylphenylimino)-4-oxo-3-thiazolidinyl] methyl}benzoic acid (7d), the best in vitro inhibitor of PTP1B and the isoform IF1 of LMW-PTP, provided the highest activation level of the insulin receptor and was found to be endowed with an excellent insulinomimetic effect on the selected cells. This compound therefore represents an interesting lead compound for developing novel PTP1B and LMW-PTP inhibitors which could be achieved by improving both its pharmacological profile and its potentiating effects on insulin signalling.

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Section: Introductionmentioning

confidence: 99%

New 4-[(5-arylidene-2-arylimino-4-oxo-3-thiazolidinyl)methyl]benzoic acids active as protein tyrosine phosphatase inhibitors endowed with insulinomimetic effect on mouse C2C12 skeletal muscle cells

Ottanà

Maccari

Amuso

et al. 2012

European Journal of Medicinal Chemistry

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“…Protein tyrosine phosphatase 1B (PTP1B), the most clearly characterized enzymatic member of the PTP superfamily, is considered as a negative factor to both Type 2 diabetes and obesity [15] [16]. Very recent studies reveal that PTP1B may also function as an oncogene in the context of breast cancer [17].…”

mentioning

confidence: 99%

Synthesis of (Glycopyranosyl‐triazolyl)‐purines and Their Inhibitory Activities against Protein Tyrosine Phosphatase 1B (PTP1B)

Luo

Shen

et al. 2011

Chemistry & Biodiversity

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Development of novel purine derivatives has attracted considerable interest, since both purine and purine-based nucleosides display a wide range of crucial biological activities in nature. We report here a novel expansion of these studies by introducing gluco- or galactopyranosyl scaffold to the N- or 9-position (or both) of 6-Cl purine moiety via Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition. By such an efficient reaction, a series of glycosyl-triazolyl-purines were successfully synthesized in good yields. Biological evaluation showed that the majority of these glycoconjugates were good PTP1B inhibitors with IC(50) values in low micromolar range (1.5-11.1 μM). The benzylated sugar derivatives displayed better inhibitory potency than that of the acetylated ones. Replacement of Cl by MeO at C(6) of the purine moiety decreased the inhibition in the case of benzylated (glycosyl-mono-triazolyl)-purines 11 and 12 (IC(50) >80 μM), whereas MeO-substituted benzylated bis[galactosyl-triazolyl]-purine 16 possessed the best inhibitory activity with an IC(50) value of 1.5 μM. Additionally, these compounds exhibited 2- to 57-fold selectivity over other PTPs (TCPTP, SHP1, SHP2, and LAR).

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“…Cellular processes controlled by them include growth, differentiation, metabolism, migration, gene transcription, ion channel activity, immune responses, apoptosis and bone development [1][2][3][4] . Unregulated activity of PTPs is responsible for several human diseases, including cancer, diabetes, obesity and dysfunction of the immune system [5][6][7] . One member of the PTP family, PTP1B, is an intracellular PTP expressed in insulin responsive tissues and shown to be a negative regulator in the insulin and leptin receptor pathways [8][9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and characterization of 5,7-dihydroxyflavanone derivatives as novel protein tyrosine phosphatase 1B inhibitors

Sun

Gao

et al. 2012

Journal of Enzyme Inhibition and Medicinal Chemistry

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Therapeutic strategies for targeting PTP1B in diabetes

Cited by 66 publications

References 46 publications

New 4-[(5-arylidene-2-arylimino-4-oxo-3-thiazolidinyl)methyl]benzoic acids active as protein tyrosine phosphatase inhibitors endowed with insulinomimetic effect on mouse C2C12 skeletal muscle cells

New 4-[(5-arylidene-2-arylimino-4-oxo-3-thiazolidinyl)methyl]benzoic acids active as protein tyrosine phosphatase inhibitors endowed with insulinomimetic effect on mouse C2C12 skeletal muscle cells

Synthesis of (Glycopyranosyl‐triazolyl)‐purines and Their Inhibitory Activities against Protein Tyrosine Phosphatase 1B (PTP1B)

Synthesis and characterization of 5,7-dihydroxyflavanone derivatives as novel protein tyrosine phosphatase 1B inhibitors

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