Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
Bioorg Med Chem. 2012 Jul 15;20(14):4371-6. doi: 10.1016/j.bmc.2012.05.040. Epub 2012 May 24.
Arylstibonates structurally resemble phosphotyrosine side chains in proteins and here we addressed the ability of such compounds to act as inhibitors of a panel of mammalian tyrosine and dual-specificity phosphatases. Two arylstibonates both possessing a carboxylate side chain were identified as potent inhibitors of the protein tyrosine phosphatase PTP-ß. In addition, they inhibited the dual-specificity, cell cycle regulatory phosphatases Cdc25a and Cdc25b with sub-micromolar potency. However, the Cdc25c phosphatase was not affected demonstrating that arylstibonates may be viable leads from which to develop isoform specific Cdc25 inhibitors.
芳基膦酸盐在结构上类似于蛋白质中的磷酸酪氨酸侧链，在这里我们研究了这些化合物作为一组哺乳动物酪氨酸和双特异性磷酸酶抑制剂的能力。两种都具有羧酸盐侧链的芳基膦酸盐被鉴定为蛋白酪氨酸磷酸酶 PTP-ß 的有效抑制剂。此外，它们以亚微摩尔的效力抑制双特异性、细胞周期调节磷酸酶 Cdc25a 和 Cdc25b。然而，Cdc25c 磷酸酶不受影响，表明芳基膦酸盐可能是开发 Cdc25 同工型特异性抑制剂的可行先导化合物。
