Novel thiophene derivatives as PTP1B inhibitors with selectivity and cellular activity

Ye, Deju; Zhang, Yu; Wang, Fei; Zheng, Mingyue; Zhang, Xu; Luo, Xiaomin; Shen, Xu; Jiang, Hualiang; Liu, Hong

doi:10.1016/j.bmc.2010.01.055

Cited by 62 publications

(27 citation statements)

References 31 publications

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“…However, astragaloside II had no apparent effects on B cell proliferation in vitro or in vivo. Compounds with a thiophene core can bind to PTP receptors with high affinity and have demonstrated extensive cellular activities [8] . We hypothesized that astragaloside II might also interact directly with T lymphocyte surface proteins, which are critical components of the TCR signaling pathway.…”

Section: Wwwchinapharcom Wan Cp Et Almentioning

confidence: 99%

Astragaloside II triggers T cell activation through regulation of CD45 protein tyrosine phosphatase activity

et al. 2013

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Aim: To investigate the immunomodulating activity of astragalosides, the active compounds from a traditional tonic herb Astragalus membranaceus Bge, and to explore the molecular mechanisms underlying the actions, focusing on CD45 protein tyrosine phosphatase (CD45 PTPase), which plays a critical role in T lymphocyte activation. Methods: Primary splenocytes and T cells were prepared from mice. CD45 PTPase activity was assessed using a colorimetric assay. Cell proliferation was measured using a [ 3 H]-thymidine incorporation assay. Cytokine proteins and mRNAs were examined with ELISA and RT-PCR, respectively. Activation markers, including CD25 and CD69, were analyzed using flow cytometry. Activation of LCK (Tyr505) was detected using Western blot analysis. Mice were injected with the immunosuppressant cyclophosphamide (CTX, 80 mg/kg), and administered astragaloside II (50 mg/kg). Results: Astragaloside I, II, III, and IV concentration-dependently increased the CD45-mediated of pNPP/OMFP hydrolysis with the EC 50 values ranged from 3.33 to 10.42 µg/mL. Astragaloside II (10 and 30 nmol/L) significantly enhanced the proliferation of primary splenocytes induced by ConA, alloantigen or anti-CD3. Astragaloside II (30 nmol/L) significantly increased IL-2 and IFN-γ secretion, upregulated the mRNA levels of IFN-γ and T-bet in primary splenocytes, and promoted CD25 and CD69 expression on primary CD4 + T cells upon TCR stimulation. Furthermore, astragaloside II (100 nmol/L) promoted CD45-mediated dephosphorylation of LCK (Tyr505) in primary T cells, which could be blocked by a specific CD45 PTPase inhibitor. In CTX-induced immunosuppressed mice, oral administration of astragaloside II restored the proliferation of splenic T cells and the production of IFN-γ and IL-2. However, astragaloside II had no apparent effects on B cell proliferation. Conclusion: Astragaloside II enhances T cell activation by regulating the activity of CD45 PTPase, which may explain why Astragalus membranaceus Bge is used as a tonic herb in treating immunosuppressive diseases.

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Section: Wwwchinapharcom Wan Cp Et Almentioning

confidence: 99%

Astragaloside II triggers T cell activation through regulation of CD45 protein tyrosine phosphatase activity

et al. 2013

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“…Similarly, addition of halogen substituents (9) that established favorable hydrophobic interactions with the lipophilic amino acid side chains (Met258, Gly259, and Phe52) gave 6-fold selectivity over TCPTP. 27 Lau et al found a potent PTP1B inhibitor 10 with an IC 50 = 0.003 lM, but no selective against TCPTP (Table 2). 28 X-ray showed that the second phosphonate is positioned to take advantage of Arg24 and Arg254.…”

Section: Hydrophobic Interactions With Phe52 Cys32 and Met258mentioning

confidence: 96%

The design strategy of selective PTP1B inhibitors over TCPTP

Wang

Shi

2016

Bioorganic & Medicinal Chemistry

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“…Examples to be considered of both natural and synthetic chemical compounds include vanadate, phenol compounds, oleanolic acid derivatives and sulfathiazole-related compounds as examples as either allosteric or active site inhibitors [57][58][59][60][61][62].…”

Section: Ptp Inhibition Studiesmentioning

confidence: 99%

pH-metric chemical speciation modeling and studies of in vitro antidiabetic effects of bis[(imidazolyl)carboxylato]oxidovanadium(IV) complexes

Gundhla

Walmsley

Ugirinema

et al. 2015

Journal of Inorganic Biochemistry

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Novel thiophene derivatives as PTP1B inhibitors with selectivity and cellular activity

Cited by 62 publications

References 31 publications

Astragaloside II triggers T cell activation through regulation of CD45 protein tyrosine phosphatase activity

Astragaloside II triggers T cell activation through regulation of CD45 protein tyrosine phosphatase activity

The design strategy of selective PTP1B inhibitors over TCPTP

pH-metric chemical speciation modeling and studies of in vitro antidiabetic effects of bis[(imidazolyl)carboxylato]oxidovanadium(IV) complexes

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