Formylchromone derivatives as a novel class of protein tyrosine phosphatase 1B inhibitors.
Formylchromone derivatives as a novel class of protein tyrosine phosphatase 1B inhibitors.
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DOI：
10.1016/s0960-894x(03)00479-7
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发表时间：
2003-08
影响因子：
2.7
通讯作者：
Yi Sup Shim;Ki Chul Kim;D. Chi;Keun-Hyeung Lee;Hyeongjin Cho
中科院分区：
文献类型：
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作者：
Yi Sup Shim;Ki Chul Kim;D. Chi;Keun-Hyeung Lee;Hyeongjin Cho
甲酰基色素抑制人蛋白酪氨酸磷酸酶PTP1B， ic50值为73 μM。甲酰色胺骨架上不同位置的取代可以调节甲酰色胺的化学反应性。在初步的构效关系评估中，最有效的抑制剂对PTP1B的ic50为4.3 μM，对其他人类PTPases， LAR和TC-PTP具有较强或中等的选择性。然而，该化合物对微生物PTPases、YPTP1和YOP没有选择性。甲酰色素衍生物的效价和选择性有望进一步提高，为治疗2型糖尿病和肥胖症的药物设计提供了新的药效团。
Formylchromone inhibits a human protein tyrosine phosphatase PTP1B with a IC50value of 73 μM. The chemical reactivity of formylchromone was adjusted by substitution at various positions of the formylchromone skeleton. In an initial assessment of the structure–activity relationship, the most potent inhibitor showed an IC50of 4.3 μM against PTP1B and strong or medium selectivity against other human PTPases, LAR and TC-PTP. This compound, however, was not selective against microbial PTPases, YPTP1 and YOP. The potency and selectivity of the formylchromone derivatives expecting further improvements provides a novel pharmacophore for the design of drugs for the treatmenrt of type 2 diabetes and obesity.