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Abstract

2, 5-DISUBSTITUTED OXADIAZOLE AND IT’S DERIVATIVE INHIBIT PROTEIN TYROSINE PHOSPHATASE PTP1B, ENHANCING INSULIN RECEPTOR PHOSPHORYLATION

Chandrashekhar L Athare*, Nirmala Singh, Chandrashekhar D Upasani

ABSTRACT

Protein tyrosine phosphatase 1B (PTP1B) is known to be a key regulator of insulin sensitivity. A series of 2, 5-disubstituted oxadiazole were synthesized and screened for the PTP1B inhibition, insulin receptor phosphorylation and for its pharmacokinetic profiles. In Enzyme-based assay for PTP1B new chemical entity-9 (NCE-9), showed a potent inhibition of PTP1B with an IC50of 0.46 μmol/L and no visible inhibitory activity for other PTP family members. NCE-9 also shows increased the insulin induced tyrosine phosphorylation of IRβ and boosted IR phosphorylation more potently. NCE-9 showed good in vivo pharmacokinetic profiles in C57BL/6J mice and SD rats. Overall, these studies suggest that NCE-9 inhibit PTP1B and enhance insulin receptor phosphorylation with good in vivo pharmacokinetic profile. It would be a new therapeutic candidate with potential for the treatment of type 2 diabetes.

Keywords: NCE-9, Protein tyrosine phosphatase 1B, IR?.


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