Design, synthesis and insulin-sensitising effects of novel PTP1B inhibitors.

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Tang YB, Lu D, Chen Z, Hu C, Yang Y, Tian JY, Ye F, Wu L, Zhang ZY, Xiao Z

Design, synthesis and insulin-sensitising effects of novel PTP1B inhibitors.

Bioorg Med Chem Lett. 2013 Apr 15;23(8):2313-8. doi: 10.1016/j.bmcl.2013.02.073. Epub 2013 Feb 26.

PubMed ID

23499238 [ View in PubMed

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Abstract

Fifteen novel sulfathiazole-related compounds were designed as PTP1B inhibitors based on a previously reported allosteric inhibitor (1) of PTP1B. These compounds were synthesized and evaluated against human recombinant PTP1B. Six compounds (3, 4, 8 and 14-16) exhibited significant inhibitory activity against PTP1B. The most active compound (16) showed IC50 value of 3.2 muM and kinetic analysis indicated that it is a non-competitive inhibitor of PTP1B. Furthermore, compound 16 demonstrated excellent selectivity to PTP1B over other PTPs. It also displayed in vivo insulin sensitizing effect in the insulin resistant mice.

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Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
3-(3,5-Dibromo-4-Hydroxy-Benzoyl)-2-Ethyl-Benzofuran-6-Sulfonic Acid [4-(Thiazol-2-Ylsulfamoyl)-Phenyl]-Amide	Tyrosine-protein phosphatase non-receptor type 1	IC 50 (nM)	8000	N/A	N/A	Details